ZMPCZM016000.11.08 Applications of TENS in the management of Patients with pain
-
Upload
painezeeman -
Category
Health & Medicine
-
view
1.005 -
download
9
Transcript of ZMPCZM016000.11.08 Applications of TENS in the management of Patients with pain
Applications of Transcutaneous Electrical Nerve Stimulation in the Management of Patients with Pain State-of-the-Art Update MERYL ROTH GERSH and STEVEN L. WOLF
Numerous publications devoted to the topic of transcutaneous electrical nerve stimulation (TENS) have appeared since the presentation of a special issue of PHYSICAL THERAPY (December, 1978). This update article addresses contemporary information on efficacy, mode of application, treatment outcomes, and neuro-physiological mechanisms relevant to this modality. Investigators have become far more specific when presenting this information in the current literature on treating acute pain conditions with TENS than they were in the literature for the 1978 special issue. Improvement has been made in providing specific details to enable replication of TENS stimulating characteristics among patients with chronic pain; yet several clinical researchers still fail to evaluate treatment outcomes adequately. Perhaps the greatest advances in our understanding of TENS involve the recent development of mechanisms that might account for how different types of TENS work. Suggestions for predicting patient responses to TENS and for avenues of future inquiry are offered.
Key Words: Electric stimulation, Pain, Physical therapy.
A wealth of information is available on the clinical application of transcutaneous electrical nerve stimulation (TENS) for pain management. In recent years, clinicians have studied the effect of TENS on pain associated with specific pathological conditions and have sought a relationship between specific treatment protocols and outcomes. Authors have more closely attended to the importance of specific electrode placements and stimulation characteristics, so that studies on particular diagnostic groups of patients could be compared and replicated. More sophisticated pain evaluation tools have been used to assess a patient's response to TENS therapy.
The purpose of this article is to review critically literature about TENS, which has been generated after the publication of a special issue on TENS in PHYSICAL THERAPY in 1978, to determine if more definitive information is available regarding 1) the efficacy of treatment for specific diagnostic categories, 2) current methods of application (specific elec
trode placements and stimulation characteristics) and their effects on treatment outcomes, and 3) neurophysiological modes of action. Topics for future clinical study will also be discussed.
TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION FOR ACUTE PAIN
One of the most successful applications of TENS is for postoperative pain control.1-11 Although treatment protocols vary between different studies, important treatment variables are fairly consistent among these studies.1 Patients are generally provided with a preoperative exposure to TENS to choose comfortable stimulation settings. Sterile electrodes are placed adjacent to the incision in surgery, and TENS treatment commences in the recovery room, with the stimulation variables set at a previously established comfort level. Transcutaneous electrical nerve stimulation is used continuously for the first 48 to 72 hours; the patient regulates the stimulus intensity to suit his needs. Treatment outcomes are measured not only by subjective pain report, but also by the type and amount of pain medication requested by the patient. Incidences of postoperative ileus and atelectasis, records on compliance with respiratory therapy regimens, and length of inten
sive care and hospital stay also provide objective measures of the patient's response to TENS treatment.
Schomburg and Carter-Baker evaluated the analgesic effect of TENS on 75 postlaparotomy patients.2 In comparing these patients with a matched control group by retrospective chart observation, the authors found that patients using TENS postoperatively required 56 percent fewer doses of pain medication during the first five postoperative days than did patients in the control group. Patients receiving TENS were more mobile and participated in breathing exercises earlier than their control group counterparts.
Ali et al studied the pulmonary function of 40 patients who had undergone cholecystectomies.3 Fifteen patients used TENS continuously for the first 48 hours postoperatively and then on an "as needed" basis. Another 15 patients did not use TENS, and a third group of 10 patients used TENS units with the batteries reversed so that no current was delivered to the patient (sham TENS). Spirometric evaluations of all patients conducted on the third and fifth postoperative days indicated that patients who were treated with TENS had significantly higher vital capacities and functional residual capacities than patients receiving either sham TENS or no TENS. Patients using TENS had a significantly decreased incidence of post-
Mrs. Gersh is a physical therapist at St. Luke's Memorial Hospital, S 711 Cowley St, Box 288, Spokane, WA 99210.
Dr. Wolf is Associate Professor, Department of Rehabilitation Medicine, Emory University School of Medicine, 1441 Clifton Rd, NE, Atlanta, GA 30322 (USA) and a senior investigator, Emory University Rehabilitation Research and Training Center, Atlanta, GA.
Address all correspondence to Dr. Wolf. This invited paper was submitted July 16, 1984,
and was accepted September 7, 1984.
314 PHYSICAL THERAPY
PRACTICE
operative pulmonary dysfunction and complications. Patients in all groups required supplemental pain medications, but those patients in the TENS group required less pain medication than did those not receiving actual TENS treatment.
Taylor and associates conducted a similar study with patients who had undergone abdominal surgery.4 Thirty patients used actual TENS and 22 patients used sham units for one hour every four hours for the first three postoperative days. Patients were permitted to request pain medication after 30 minutes of TENS treatment if the treatment did not adequately control pain. Twenty-five patients served as a control group. Taylor and associates noted that patients receiving TENS or sham TENS required less pain medication and ambulated earlier than did those patients in the control group.4 The results highlighted the placebo potential of TENS but may also be explained by the non-continuous mode of TENS application.
Another study examined the analgesic effect of TENS on patients who had undergone upper abdominal surgery.6
The patients who used TENS for postoperative pain control required 30 times less pain medication than did those in the control group. Improved pulmonary function, appetite, and ambulation indicated an earlier recovery for those patients who used TENS than for those patients who did not. Because the report of this study lacked information on treatment protocol and technique, replicating or comparing these results with similar studies is impossible.
Several investigators have studied the efficacy of TENS for management of postlaminectomy pain.7-9 In all these studies, electrodes were placed parallel to the incision, stimulation was set at comfortable levels, TENS was used continuously for at least the first 24 to 48 hours, and the treatment was discontinued after that period at each patient's request. The investigators all reported a significant decrease in the strength and amount of pain medication requested by the patients using TENS in comparison with those patients not using TENS. Solomon et al reported that TENS appeared most effective in "drug-naive" patients, those who had not used narcotics preoperatively for more than two weeks in the six months before surgery.7 Furthermore, they noted that poor pain relief was reported by drug-
experienced patients, regardless of whether TENS or narcotics were used. This occurrence may suggest a cross-tolerance between narcotics and TENS and activation of a similar neural substrate to explain the analgesic effect of both TENS and opioid derivative medications.
Richardson and Siquiera carefully recorded the stimulation settings used.8
They observed no correlation between specific pulse widths, rates, or stimulus intensities and the degree of pain relief reported. Other investigators have corroborated this finding.12
Additional benefits of postoperative pain management with TENS may be realized by the postcesarean patient. Nonnarcotic pain control by use of TENS may facilitate earlier mother-infant bonding. Drug-induced side effects such as nausea, drowsiness, and respiratory depression are limited. Narcotics are not passed to the baby by breastfeeding. Pulmonary rehabilitation is facilitated and reduces the occurrence of pulmonary complications in the mother.10
Harvie cited rehabilitation benefits when using TENS to control postoperative pain after knee surgery.11 He studied patients who had undergone total knee replacements, synovectomies, meniscectomies, arthrotomies, patchplasties, or fracture reductions. Electrodes placed over the medial and lateral collateral ligaments provided the most effective pain control. Narcotic use was decreased by 75 to 100 percent. Recovery of quadriceps femoris muscle strength and knee range of motion (ROM) was facilitated. Four of seven patients with total knee replacements achieved 80 to 90 degrees of active knee flexion by the sixth postoperative day; the other three patients achieved the same goal by the eighth postoperative day. Earlier ambulation and decreased length of hospital stay were also reported. Clearly, TENS for management of postoperative knee pain is an important adjunct to a rehabilitation program.
Transcutaneous electrical nerve stimulation can also be applied for control of acute dental pain.13, 14 Hansson and Ekblom evaluated 62 patients admitted to an emergency dental clinic with acute pain secondary to pulpal inflammation, apical periodontitis, or postoperative pain after tooth extraction.13 Patients were randomly assigned to one of three groups: those receiving high frequency
TENS (100 Hz; n = 22); those receiving low frequency TENS (2 Hz; n = 20); and those receiving a placebo treatment (batteries removed from the unit; n = 20). Electrodes were placed on the face over the painful area. Stimulus intensity was set to three times the sensory threshold for patients in the high frequency group, and three to five times sensory threshold for those receiving low frequency TENS. This latter group experienced muscular contractions associated with the higher intensity. Patients used a visual analog scale to record their pain intensity before, during, and after treatment. Seven of 22 patients (31.8%) in the high frequency group reported pain relief of greater than 50 percent after 30 minutes of treatment, compared with 9 of 20 patients (45%) in the low frequency group, and 2 of 20 (10%) in the placebo group. Pain returned within 10 minutes after treatment in 4 of 7 patients in the high frequency group, and in 2 of 9 patients in the low frequency group. The 2 patients in the placebo group who reported initial relief experienced longer lasting relief. Two other patients in the high frequency group and 2 in the low frequency group reported complete pain relief after treatment. Differences in the analgesic effectiveness of TENS demonstrated between the high and low frequency groups were not significant. The effectiveness of TENS for pain control, however, was significantly greater when either experimental group was compared with the placebo group. Pain control of longer duration might have occurred if treatment duration could have been longer than 30 minutes.
Transcutaneous electrical nerve stimulation is being used, especially outside of the United States, to control acute pain associated with labor and delivery.15, 16 Erkola et al evaluated 100 patients who used TENS for pain management during the first stage of labor.15
Electrodes were placed paravertebrally at T10-11 and S2-4. Stimulus intensity was set at a tolerable submotor threshold and regulated by the patient. Thirty-one percent of the patients reported good pain relief, and 55 percent reported moderate relief within one hour of initiating treatment. Details of the pain rating procedure were not described. Patients using TENS, however, requested a similar amount of pain medication during labor in comparison with a control group who did not use TENS.
Volume 65 / Number 3, March 1985 315
Jones reported that 82 percent of the patients in labor using TENS had substantial relief of back labor pain and 71 percent had significant relief of abdominal labor pain during the first stage of labor.16 Again, methods used to measure pain were not described. During the second stage of labor, TENS was frequently discontinued because it interfered with the patient's controlled breathing and pushing efforts. Transcutaneous electrical nerve stimulation also interfered with continuous fetal monitoring. The use of TENS did not affect the length of labor or immediate postnatal health of the infant.
Further investigation of the role of TENS in the management of labor pain is warranted with close attention paid to application techniques and measurement of treatment outcome. Reduction of the need for narcotics during labor could contribute to the improved perinatal and postnatal health of the mother and the improved respiratory and neurological status of the newborn child.
Methods of application for TENS to control acute pain are summarized in Table 1. All but one report provide specific electrode placements for particular pain locations. Ranges are given most
frequently to describe stimulation settings used, and the frequency and duration of TENS treatment is reported. The provision of application details in recent literature allows more accurate comparison and replication of clinical research.
Table 2 summarizes the evaluation tools used to assess TENS treatment outcomes for acute pain management. A variety of subjective pain rating scales and recording of pain medication intake were used most commonly to assess the analgesic effect of TENS. In three studies, additional credence was given to favorable treatment outcomes by use of objective physical evaluations, such as pulmonary function studies or joint range-of-motion measurements. In addition to the patients' reports of pain, objective evaluation procedures enhance the reliability and validity of these clinical studies.
Recent literature has been favorable on the efficacy of TENS for acute pain control. The location and description of acute pain is usually precise and allows for use of a more specific treatment approach. Homogeneous groups of patients (eg, those with postoperative pain) and matched control groups are readily
available for evaluation. Treatment outcomes may be objectively measured in terms of medication intake, respiratory status, rehabilitation factors, and subjective pain ratings. These advantages are not as readily available when studying the management of chronic pain and may explain the wide variation in response to TENS treatment among chronic pain patients.
TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION FOR CHRONIC PAIN
Studies examining patients with widely divergent diagnoses or symptom complexes are not as prevalent in the TENS literature today as they were several years ago. These studies can provide valuable information in selecting which diagnostic groups of patients respond most favorably to TENS for pain relief.
Wolf and colleagues evaluated the responses to TENS of 114 patients with chronic pain.12 Patients reported pain secondary to peripheral neuropathy, peripheral nerve injury, radiculopathy, or musculoskeletal trauma. Electrodes were systematically placed at the painful
TABLE 1 Transcutaneous Electrical Nerve Stimulation Application Methods for Acute Pain
Primary Author
Schomburg2
Ali3
Taylor4
Sodipo6
Solomon7
Richardson8
Schuster9
Riley10
Harvie11
Hansson13
Erkola15
Jones16
Diagnosis
postlaparotomy
postcholecystectomy
postlaparotomy postlaparotomy postoperative
postlaminectomy
postlaminectomy
postcesarean section
postoperative knee pain
dental pain
labor pain
labor pain
Electrode Placement
parallel to incision
parallel to incision
parallel to incision parallel to incision 1.0 cm parallel to
incision 5 cm parallel to
incision
2.5 cm parallel to incision
above and below incision
over medial and lateral collateral ligaments
over painful site
paraspinal T10-L1, S2-S4
Pulse Width (µ see)
120-340
128-200
80
72.5-240.0
40-100
250-400
200
84
Pulse Rate (PPS)
10-100
10-100
40
8.7-240
25-100
80-100
100
2
Intensity
0-90 V (comfort)
0-135 mA (comfort)
comfort
0.2-38.5 mA
0-90 V
20-35 mA
comfort
2-3 times sensory threshold or
3-5 times sensory threshold
20-25 V (comfort)
comfort
Frequency and Duration of Treatments
constant for first 48 hr, then as needed
constant for first 48 hr
60 min every 4 hr
constant for first 48 hr
within first 20 hr postoperatively, for 3-12 days
constant for first 18-24 hr
constant, or 30 min four times a day
30 min
30 min
during first stage of labor
during first stage of labor
316 PHYSICAL THERAPY
PRACTICE
TABLE 2 Evaluation Methods for Transcutaneous Electrical Nerve Stimulation Treatment for Acute Pain
Primary Author
Schomburg2
Ali3
Taylor4
Sodipo6
Solomon7
Richardson8
Schuster9
Riley10
Harvie11
Hansson13
Erkola15
Jones16
Diagnosis
postlaparotomy
postcholecystectomy
postlaparotomy postlaparotomy postoperative postlaminectomy
postlaminectomy
postcesarean section
postoperative knee pain
dental pain labor pain labor pain
Subjective Pain Rating
yes
no
yes no yes yes
yes
yes
no
yes yes yes
Pain Medication Taken
yes
yes
yes yes yes yes
yes
yes
yes
no yes yes
Physical Evaluations
spirometry, arterial blood gases
pulmonary functions
none
none
none
knee range of motion, straight leg raise, early ambulation
none none none
Other
resumption of activities
postoperative complication
resume ambulation resume ambulation
length of hospital stay
postoperative complication
site or on related nerve roots or peripheral nerves. Stimulation variables were set to evoke a strong but comfortable sensation in the painful region, and exact electrical settings were recorded. Treatments were conducted on an outpatient basis and were of 30- to 45-minute duration. Patients rated their pain intensity on a 10-cm line before, during, and immediately after treatment. In addition, some patients completed the pain descriptor word list found in the McGill Pain Questionnaire.17 Thirteen of 18 patients (72%) with peripheral neuropathy, 6 of 21 patients (28.5%) with peripheral nerve injury, 8 of 36 patients (22%) with radicular pain, and 15 of 39 patients (38.4%) with musculoskeletal pain reported more than 60 percent relief of pain after TENS treatment.12 In the peripheral neuropathy group, patients with postherpetic neuralgia responded most favorably to TENS. Patients with fewer previous analgesic treatments, no surgical intervention, and limited narcotic use responded more favorably than those patients with numerous previous treatments. We found no significant relationship between specific electrode placements or stimulation settings and treatment outcomes, but patients with radiculopathy or peripheral nerve injury responded better to higher intensity stimulation. This observation was also reported by Melzack in treating patients with chronic low back pain.18 Follow-
up evaluations on 25 patients who used TENS at home for one month generally indicated decreased benefits from treatment as time progressed. These decreased benefits may have been due to reduced patient compliance when independent TENS application became a requirement.
Another investigation studied 98 patients with back pain, headache, or a variety of other pain symptoms.19 Patients used TENS at home, placing electrodes at the site of pain, and setting stimulation intensity at a comfortable level. Patients recorded their own subjective pain level before and after treatment. After 12 days of home treatment, 69 percent of the patients with low back pain, 40 percent of those with headache pain, and 60 percent of those with pain from other sources reported more than 50 percent relief of pain. The authors failed to describe stimulation settings, pain-rating measures, and duration and frequency of treatment; they also did not control for a wide variation in application techniques based on patient competence and compliance. Thus, this study provided little valuable information on TENS for chronic pain control.
Santiesteban described the use of low frequency TENS (2-4 Hz) for treatment of spinal pain.20 Stimulus pulse width was set at the maximum for the units used, and intensity was set at 50 mA to evoke a muscle contraction within pain tolerance. Electrodes were placed 2.5 to
5 cm from the appropriate spinous process in a parallel or crossed configuration. Distal acupuncture points were also stimulated. Patients required less analgesic medication when TENS was used to control pain.
Melzack and colleagues recently compared the analgesic effects of TENS and massage in a double-blind study of 41 patients with chronic low back pain.21
Transcutaneous electrical nerve stimulation electrodes were placed in the center of the back and on the lateral thigh. Low frequency stimulation (4-8 Hz) with a strong but tolerable intensity was applied. The massage was performed with a suction cup apparatus. Treatment was given two times a week for 30 minutes, for a maximum of 10 treatments. Treatment outcomes were evaluated using both the present-pain intensity (PPI) scale and the pain-rating index of the McGill Pain Questionnaire.17 Bilateral straight leg raising (SLR) and lumbosacral flexion were also measured. Transcutaneous electrical nerve stimulation produced a significantly greater improvement than massage in the pain-rating and the PPI scales and in the bilateral SLR measures for these patients.21
Transcutaneous electrical nerve stimulation has been used with various degrees of success in the management of arthritic pain. Taylor et al evaluated the effect of TENS on osteoarthritic knee pain.22 Patients used actual TENS or a
Volume 65 / Number 3, March 1985 317
TABLE 3 Transcutaneous Electrical Nerve Stimulation Application Methods for Chronic Pain
Primary Author
Wolf12
Moore19
Santiesteban20
Melzack21
Taylor22
Winnem27
Kahn29
Gersh24
Diagnosis
varied
varied
spine pain
low back pain
osteoarthritis of knee
phantom limb pain
nonunited fracture
peripheral neuropathy
Electrode Placement
site of pain, related nerve roots, or peripheral nerve
varied
paravertebral
center of back and lateral thigh
about knee
stump or contralateral limb
over fracture site in crossed pattern
along nerve trunk at site of pain
Pulse Width (µ sec)
100
midrange
maximum
300
200
Pulse Rate (pps)
50-100
10-100 or 1-4
2-4
4-8
comfort
100 or 2
minimum
110
Intensity
submotor threshold
comfort
motor threshold (50 mA)
to tolerance
comfort
sensory threshold (less than 20 mA)
26-28 mA
Frequency and Duration of Treatments
30-45 min, 3-5 times a week
30-60 min daily or as needed
30-60 min
30 min, 2 times a week
30-60 min as needed
15 min twice a day
30-60 min, 3-4 times a day
continuous, 8-10 hr a day
placebo unit wired to produce various sounds in a well-monitored home program. After two weeks of home treatment, patients were reevaluated and sent home to use the other (TENS or placebo) unit for another two weeks. Patients were evaluated again and permitted to take home the most beneficial unit for one more month of home treatment. Responses to treatment were evaluated by subjective pain rating, ambulation distance, and analgesic medication intake. The actual TENS provided significantly more pain relief than did the placebo unit in both subjective and medication analyses. Patients reported the greatest pain relief while wearing the active TENS unit. Relief frequently lasted for several hours after treatment was completed. Several patients continued to use the TENS at home for several months. They reported decreasing pain relief over time, possibly because of increasing joint deterioration.
Transcutaneous electrical nerve stimulation may be an important adjunct in the rehabilitation of arthritic patients, particularly when joint replacement is not possible. In patients with chronic systemic diseases who may be receiving a variety of pharmacologic and therapeutic treatments concurrently, the clinician must be alert, however, to adverse reactions to TENS, as reported by Griffin and McClure.23
Patients with a variety of peripheral neuropathic conditions including peripheral neuropathy,24 postherpetic neuralgia, peripheral nerve injury, reflex sympathetic dystrophy,25 and Sudeck's atrophy26 have all responded favorably to TENS treatment. Transcutaneous electrical nerve stimulation has also proven effective in the management of phantom limb pain27 and the distal burning paresthesia associated with Guillain-Barré syndrome.28
Kahn provided radiographic evidence that TENS facilitated callous formation and osseous bridging at sites of non-united fractures in three patients.29
Transcutaneous electrical nerve stimulation was originally applied to control pain in these patients for nonunited fractures six months after injury. Electrodes were placed in various configurations to "sandwich" the fracture site. Pulse width was set for the longest "on" time, pulse rate was set at the lowest available frequency, and stimulus intensity was set at the sensory threshold. Increased callous formation was noticed on radiographic examination after one month of treatment in one patient and after 10 weeks of treatment in the other two patients.
Millea described another unusual application of TENS.30 A 50-year-old patient with an eight-year history of non-operative abdominal pain and disten
tion was relieved of this discomfort after using TENS for five days. This relief may be attributed to decreased sympathetic tone and increased gastric motility associated with TENS application.31
Owens et al observed local vasodilation and skin temperature increases of 1°C when TENS was applied at the ulnar groove and wrist in seven healthy subjects.31 Such evidence also may explain the mechanism of pain relief in patients with causalgia or reflex sympathetic dystrophy. Consistent sympathetic nervous system responses, however, have not, as yet, been recorded among a variety of patients.25
Table 3 summarizes the application procedures used for chronic pain control with TENS. Significant effort has been made by most investigators in recent years to specify effective electrode placements and stimulating settings. Although specific pulse widths, rates, and intensities are not always cited, most reports provide a description of the sensory or motor responses elicited by TENS during treatment. Treatment duration was usually 30 to 60 minutes, but the frequency of treatment varied with each study. Replication of clinical studies is facilitated when these procedures are described in detail.
Perhaps the weakest aspect of the clinical study of TENS for chronic pain control is evaluation of treatment out-
318 PHYSICAL THERAPY
PRACTICE
comes. Table 4 illustrates that most investigators still rely solely on the patient's report of pain to establish the efficacy of TENS treatment. Often, the pain-rating scale used by the patient is not described in detail. The great variety of pain symptoms, locations, previous and concomitant treatments, medications, and psychological components associated with chronic pain make objective evaluation much more difficult than in patients with acute pain. Use of physical measures, such as joint motion, strength, muscle girth, and participation in functional activities, however, would enhance the objective evaluation of the efficacy of TENS for chronic pain control.
PREDICTING RESPONSE TO TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION TREATMENT
Successful use of TENS for pain control may be increased as more specific patient evaluation and selection criteria are established. Reynolds and associates examined the predictive value of pain questionnaires in selecting patients who would be more likely to respond favorably to TENS treatment.32 Their evaluation indicated that older, retired patients, who had pain of less than one year duration, who had undergone limited or no surgery, and who used nonnarcotic analgesics were more likely to experience pain relief with TENS. Site
of injury, sensory deficit, and secondary gain by financial compensation for injury did not affect response to treatment. The pain questionnaire, however, seemed to have less predictive value for TENS than for other treatment regimens.
In another study, Johansson et al suggested that patients with neurogenic pain responded more favorably to TENS than did patients with somatogenic or psychogenic pain.33 Patients with pain in the extremities seemed to derive more relief with TENS than patients with axial pain. The patient's age, sex, and pain intensity did not relate to his response to treatment.
Richardson and colleagues explained how treatment with TENS could confirm a diagnosis of functional pain compared with organic pain.34 Many patients with suspected functional pain reported increased pain during and after TENS treatment. Pain was relieved with a saline injection in the majority of these patients.
Mannheimer compiled a list of factors that hinder, enhance, or restore the effectiveness of TENS for pain control.35
Among those factors that enhance TENS effectiveness are careful, continuous patient evaluation for most effective electrode placement sites and stimulation settings; changing stimulation modes and characteristics; gradually increasing patient tolerance to stronger stimulation in the painful area; elec
trode placement on motor points or superficial aspects of nerves; weaning patients from addictive medications before treatment; and educating the patient in the proper use of the modality for home treatment. Incorporating these selection and treatment criteria into treatment protocols and recording which patients most favorably respond to TENS will increase the successful use of this modality in the future.
NEUROPHYSIOLOGICAL MODES OF ACTION
Several years ago, the options available to explain the possible neurophysio l o g y mechanisms through which TENS could affect pain perception were limited.36 The prevailing explanation for most pain attenuating interventions cited the spinal gate concept developed by Melzack and Wall in 1965.37 Briefly, this notion took into account existing electrophysiological data from animal experiments that had demonstrated differential effects of collateral axons from large diameter afferent fibers mediating touch and pressure and from small diameter afferent fibers conveying nociceptive input upon interneurons within the substantia gelatinosa (Fig. 1). These interneurons could be facilitated through predominantly large diameter collateral afferent input and inhibited through primarily collateral axons from the small diameter system. In addition, the interneuron was inhibitory onto the
TABLE 4 Evaluation Methods for Transcutaneous Electrical Nerve Stimulation Treatment for Chronic Pain
Primary Author
Wolf12
Moore19
Santlesteban20
Melzack21
Taylor22
Winnem27
Kahn29
Gersh24
Diagnosis
varied
varied spine pain low back
pain
osteoarthritis of knee
phantom limb pain
nonunited fracture
peripheral neuropathy
Subjective Pain Rating
McGill Pain Questionnaire
yes no McGill Pain
Questionnaire
yes
yes
yes
yes
Pain Medication Taken no
no yes no
yes
no
no
no
Physical Evaluations
none
none none straight leg raise,
lumbosacral range of motion
roentgenogram, ambulation distance
none
roentgenogram
none
Other
resume functional activities
Volume 65 / Number 3, March 1985 319
Periphery Spinal Cord Lamina II & III
Spinal Cord Lamina V
Fig. 1. Schematic diagram depicting the Melzack-Wall gate theory of pain. Open circles represent facilitator/ synapses; closed circles indicate inhibitory synapses. Abbreviations SG = substantia gelatinosa; T = transmission cells.
terminals of both afferent fiber classes. Consequently, when large diameter afferent fiber activation was of greater frequency and intensity than smaller diameter fiber input, the inhibitory interneurons would be activated to presynaptically inhibit transmission centrally from both the noxious and nonnoxious inputs. The gate would be closed. Of course, the opposite effect would predominate if greater transmission occurred through the smaller diameter system.
This gating theory was subjected to considerable criticism because it conceptually failed to account for pain relief among a variety of clinical conditions. Nonetheless, the test of time has proven that the framework for the theory has formed the basis for several more contemporary explanations of pain alleviation through TENS. Specifically what the Melzack-Wall model brought to the attention of scientists and clinicians was the recognition that pain perception could be modulated somewhere within the neuraxis if the appropriate stimuli could be delivered and the appropriate neural substrate on which such stimuli might act could be found.
A spinal gate that conceptually follows the original model might incorporate conventional TENS (low intensity, high frequency stimuli) to effect pain reduction among patients with a diagnosis of postherpetic neuralgia. This disease process causes selective degeneration among large diameter peripheral axons. The success with conventional TENS may reside in the activation of
remaining large afferent fibers or those in close proximity to the painful site but which enter the neuraxis at the same or nearby segments as the ongoing noxious input.38 A similar explanation may be appropriate to explain how pain following certain kinds of peripheral nerve injury may respond to conventional TENS.39
Recently, clinicians have recognized that conventional TENS may not be the most effective form of stimulation for certain types of chronic pain. This thought was promoted when Ericksson and co-workers identified a large group of patients with chronic pain who showed further improvement in reduced pain perception when conventional TENS was supplemented by acupuncture-like TENS (low frequency, high intensity stimulation).40 This latter form of stimulation showed effects that were reversible through the administration of the opioid antagonist, naloxone hydrochloride; this reversal suggests that the
effects of acupuncture-like TENS might be mediated through an endogenous opiate system within the neuraxis.41 Previously, Mayer and colleagues had demonstrated that the effectiveness of acupuncture was also reversed by naloxone hydrochloride.42 These clinical findings prompted a comprehensive search for the neural substrates mediating the responsiveness of chronic pain patients to high intensity cutaneous stimulation.
At the same time, a variety of opiate receptors and numerous loci of endogenous opiates were being discovered in many human and subhuman primate studies.43 A logical marriage from this exponentially increasing body of knowledge resided in establishing relationships between neurophysiological and neu-rohistochemical studies on pain mechanisms and opiate substances, respectively. The mechanism first proposed by Basbaum and Fields in 1978 served to collate known histochemical and physiological data to explain how high intensity cutaneous electrical stimulation (for example, acupuncture-like TENS, brief-intense TENS, or burst trains of TENS) might activate endogenous opiates to alleviate pain.44
This modulatory mechanism is essentially a negative feedback loop that is schematically illustrated in Figure 2. Ongoing pain input and the discomfort often associated with high intensity TENS activate ascending pathways leading to conscious awareness of pain. Certain axons within the ascending system are known to form a synapse within medullary reticular formation nuclei, and from these nuclei, this input is transmitted to the periaqueductal gray region of the midbrain (mesencephalon). This location is exceptionally endowed with high concentrations of endogenous opiates, and when it is activated, either through natural cutaneous
Central Nervous System
Fig. 2. Schematic diagram of negative feedback loop within the neuraxis activated by noxious input.
320 PHYSICAL THERAPY
PRACTICE
stimulation, iontophoretically applied morphine, or through direct stimulation, its efferent axons form a synapse with nuclei (raphe magnus and reticularis magnocellularis) within the medulla oblongata. Output from these nuclear groups descends through the dorsolateral funiculus of the spinal cord to make enkephalinergic synapses known to inhibit the spinal transmission of Substance P, a polypeptide implicated as a neurotransmitter between axons conveying noxious information.45 This last neural interaction completes the negative feedback loop to modulate ongoing or subsequent noxious input. For further details, please refer to the Pain: Mechanism: B. Basic section within the Bibliography.
Another mechanism that may account for some aspects of pain modulation with TENS involves what LeBars et al have termed "diffuse noxious inhibitory controls," or DNIC.46 Within this system, responses elicited through continuous pain input to convergent dorsal horn neurons may be suppressed effectively by noxious or intense cutaneous stimulation, when it is applied almost anywhere on the body surface. Responses obtained through activity within the small diameter afferent fiber groups are inhibited, but nonnoxious activation of the same convergent cells or nonconvergent cells responsive to only noxious stimuli remain unaffected. Within animal models, spinalization eliminates DNIC, thereby suggesting that descending supraspinal influences are required to activate this system. Furthermore, the DNIC mechanism is sensitive to naloxone hydrochloride; this sensitivity indicates an endorphin link.47
Whether this linkage occurs at spinal or supraspinal levels has yet to be determined. Also, definitive data to test the validity of the DNIC model in man have yet to be presented.
Nonetheless, the mechanisms described in this article form plausible explanations for the way in which high intensity TENS might modulate pain perception. Other mechanisms have been proposed, but both the quantity and quality of research led us to refrain from addressing these in this article. Undoubtedly, as more data evolve and his-tochemical and electrophysiological techniques gain sophistication, additional ways of speculating on or comprehending how TENS modulates pain perception will be forthcoming.
AREAS FOR FUTURE STUDY
To facilitate the continued effective use of TENS for pain control, several areas of study must be pursued. Patient evaluation and selection criteria should be validated and refined to increase successful treatment with TENS, particularly in patients who have chronic pain. Specific electrode placements and stimulation characteristics must be evaluated in relation to specific disease entities to establish more effective treatment protocols. Clinicians should continue to evaluate the benefits of high versus low frequency stimulation, auriculother-apy,48 and acupuncture point stimulation. Use of TENS for acute pain control should be expanded within areas where it is apparently effective (eg, postoperative pain, labor and delivery pain, and pain from acute injury48). Adverse
responses to treatment such as contact dermatitis49, 50 should be reported so that hypoallergenic materials can be developed in the manufacturing of electrodes and conductive media, and so that patients at high risk for negative responses to treatment may be screened.23 Ongoing evaluation of long-term use of TENS by chronic pain patients may yield information on long-term effectiveness and clarify the neurophysiology on which treatment is based. The expanding body of knowledge resulting from applied and basic research on neurochemical and physiological bases for pain control must address the modus operandi of TENS, taking into account the stimulus characteristics applied within experimental protocols and how the relationship between stimulation and response explains the efficacy of this modality.
REFERENCES
1. Santiesteban AJ, Sanders BR: Establishing a postsurgical TENS program. Phys Ther 60:789-791, 1980
2. Schomburg FL, Carter-Baker SA: Transcutaneous electrical nerve stimulation for post-laparotomy pain. Phys Ther 63:188-193, 1983
3. Ali J, Yaffe CS, Serrette C: The effect of transcutaneous electrical nerve stimulation on postoperative pain and pulmonary function. Surgery 89:507-512, 1981
4. Taylor AG, West BA, Simon B, et al: How effective is TENS for acute pain? Am J Nurs 83:1171-1174, 1983
5. Bussey JG, Jackson A: TENS for Postsurgical Analgesia. Read at the Meeting of the Biofeedback Society of Georgia, Atlanta, GA, November 16, 1982
6. Sodipo JOA, Adedeji SA, Olumide O: Postoperative pain relief by TENS. Am J Chin Med 8:190-194, 1980
7. Solomon RA, Viernstein MC, Long DM: Reduction of postoperative pain and narcotic use by transcutaneous electrical nerve stimulation. Surgery 87:142-146, 1980
8. Richardson RR, Siquiera EB: Transcutaneous electrical neurostimulation in postlaminectomy pain. Spine 5:361-365, 1980
9. Schuster GD, Infante MC: Pain relief after low back surgery: The efficacy of TENS. Pain 8:299-302, 1980
10. Riley JE: The impact of TENS on the postcesarean patient. Journal of Obstetrics, Gynecology, and Neonatal Nursing 11:325-329, 1982
11. Harvie KW: A major advance in the control of postoperative knee pain. Orthopedics 2:129-131,1979
12. Wolf SL, Gersh MR, Rao VR: Examination of electrode placements and stimulating parameters in treating chronic pain with conventional transcutaneous electrical nerve stimulation. Pain 11:37-47, 1981
13. Hansson P, Ekblom A: TENS as compared to placebo TENS for relief of acute orofacial pain. Pain 15:157-165, 1983
14. Pertovaara A, Kemppainen P, Johansson G, et al: Dental analgesia produced by nonpainful low frequency stimulation is not influenced by stress or reversed by naloxone. Pain 13:379-384,1982
15. Erkola R, Pikkola P, Kanto J: Transcutaneous nerve stimulation for pain relief during labor: A controlled study. Ann Chir Gynaecol 69:273-277, 1980
16. Jones MCMH: Transcutaneous nerve stimulation in labor. Anaesthesia 35:372-375, 1980
17. Melzack R: The McGill Pain Questionnaire: Major properties and scoring methods. Pain 1:277-299, 1975
18. Melzack R: Prolonged relief of pain by brief intense transcutaneous somatic stimulation. Pain 1:357-373, 1975
19. Moore DE, Blacker HM: How effective is TENS for chronic pain? Am J Nurs 83:1175-1177, 1983
20. Santiesteban AJ: The role of physical agents in the treatment of spine pain. Clin Orthrop 179:24-30, 1983
21. Melzack R, Vetere P, Finch L: Transcutaneous electrical nerve stimulation for low back pain: A comparison of TENS and massage for pain and range of motion. Phys Ther 63:489-493, 1983
22. Taylor P, Hallett M, Flaherty L: Treatment of osteoarthritis of the knee with transcutaneous electrical nerve stimulation. Pain 11:233-240, 1981
23. Griffin JW, McClure M: Adverse reactions to transcutaneous electrical nerve stimulation in a patient with rheumatoid arthritis. Phys Ther 61:354-355,1981
24. Gersh MR, Wolf SL, Rao VR: Evaluation of transcutaneous electrical nerve stimulation for pain relief in peripheral neuropathy: A clinical documentation. Phys Ther 60:48-52,1980
25. Meyerson BA: Electrostimulation procedures, effects, presumed rationale and possible mechanisms. Advances in Pain Research and Therapy 5:495-534, 1983
26. Bodenheim R, Bennett JH: Reversal of a Su-deck's atrophy by the adjunctive use of transcutaneous electrical nerve stimulation: A case report. Phys Ther 63:1287-1288, 1983
27. Winnem MF, Amundsen T: Treatment of phantom limb pain with transcutaneous electrical nerve stimulation. Pain 12:299-300, 1982
28. McCarthy JA, Zigenfus RW: Transcutaneous electrical nerve stimulation: An adjunct in the pain management of Guillain-Barre Syndrome. Phys Ther 58:23-24, 1978
Volume 65 / Number 3, March 1985 321
29. Kahn J: Transcutaneous electrical nerve stimulation for nonunited fractures: A clinical report. Phys Ther 62:840-844, 1982
30. Millea TP: Transcutaneous electrical nerve stimulation in the management of nonoperative intra-abdominal pain: A case report. Phys Ther 63:1280-1282, 1983
31. Owens S, Atkinson ER, Lees DE: Thermographic evidence of reduced sympathetic tone with transcutaneous nerve stimulation. Anesthesiology 50:62-65, 1979
32. Reynolds AC, Abram SE, Anderson RA, et al: Chronic pain therapy with TENS: Predictive value of questionnaires. Arch Phys Med Re-habil 64:311-313, 1983
33. Johansson F, Almay BGL, Von Knorring L, et al: Predictors for the outcome of treatment with high frequency transcutaneous electrical nerve stimulation in patients with chronic pain. Pain 9:55-61, 1980
34. Richardson RR, Arbit J, Siquiera EB, et al: Transcutaneous electrical neurostimulation in functional pain. Spine 6:185-188,1981
35. Mannheimer JS: Enhancing the Effectiveness of TENS: Factors that Hinder, Enhance, and Restore Effectiveness. Read at the National
Pain Symposium, Indianapolis, IN, September 11-15,1982
36. Wolf SL: Perspectives on central nervous system responsiveness to transcutaneous electrical nerve stimulation. Phys Ther 58:1443-1449, 1978
37. Melzack R, Wall PD: Pain mechanisms: A new theory. Science 150:971-979,1965
38. Nathan PW, Wall PD: Treatment of post herpetic neuralgia by prolonged electric stimulation. Br Med J 3:645-647, 1974
39. Meyer GA, Fields HL: Causalgia treated by selective large fibre stimulation of peripheral nerve. Brain 95:163-168, 1972
40. Ericksson MBE, Sjölund BH, Nielźen S: Long term results of peripheral conditioning stimulation as an analgesic measure in chronic pain. Pain 6:335-347, 1979
41. Sjölund BH, Ericksson MBE: The influence of naloxone on analgesia produced by peripheral conditioning stimulation. Brain Res 173:295-301,1979
42. Mayer DJ, Price DD, Rafii A: Antagonism of acupuncture analgesia in man by the narcotic antagonic naloxone. Brain Res 121:368-372, 1977
43. Olson GA, Olson RD, Kastin AJ, et al: Endogenous opiates: 1981. Peptides (Fayetteville) 3:1039-1073
44. Basbaum Al, Fields HL: Endogenous pain control mechanisms: Review and hypothesis. Ann Neurol 4:451-462, 1978
45. Basbaum Al: The generation and control of pain. In Grossman RG, et al (eds): The Clinical Neurosciences. New York, NY, Churchill Livingstone Inc. 1983, vol 5, pp 301-324
46. LeBars D, Dickenson AH, Besson JM: Diffuse noxious inhibitory control (DNIC): I. Effects on dorsal horn convergent neurons in the rat. Pain 6:283-304, 1979
47. LeBars D, Chibour D, Kraus E, et al: Effect of naloxone upon diffuse noxious inhibitory controls (DNIC) in the rat. Brain Res 204:387-402, 1981
48. Paris DL, Baynes F, Gucker B: Effects of the Neuroprobe in the treatment of second-degree ankle inversion sprains. Phys Ther 63:35-40, 1983
49. Bolton L: TENS electrode irritation. J Am Acad Dermatol 8:134-135, 1983
50. Zugenman C: Dermatitis from TENS. J Am Acad Dermatol 6:936-939,1982
BIBLIOGRAPHY
PAIN: TENS
1. Abram SE, Reynolds AC, Cusick FJ: Failure of naloxone to reverse analgesia from transcutaneous electrical stimulation in patients with chronic pain. Anesth Analg 60:81-84, 1981
2. Berlant SR: Method of determining optimal stimulation sites for transcutaneous electrical nerve stimulation. Phys Ther 64:924-928, 1984
3. Besson JM, Chitour D, Dickenson AH, et al: Involvement of endogenous opiates in diffuse noxious inhibitory controls. J Physiol (Lond) 300:26, 1980
4. Bodenheim R, Bennett JH: Reversal of a Sudeck's atrophy by the adjunctive use of transcutaneous electrical nerve stimulation: A case report. Phys Ther 63:1287-1288,1983
5. Bohm E: Transcutaneous electrical nerve stimulation in chronic pain after peripheral nerve injury. Acta Neurochir (Wien) 40:277-283, 1978
6. Butikofer R, Lawrence PD: Electrocuta-neous nerve stimulation—II: Stimulus waveform selection. IEEE Trans Biomed Eng 26:69-75, 1979
7. Chung JM, Fang ZR, Cargill CL, et al: Prolonged, naloxone-reversible inhibition of the flexion reflex in the cat. Pain 15:35-53,1983
8. Doliber CM: Role of the physical therapist at pain treatment centers: A Survey. Phys Ther 64:905-909, 1984
9. Fried T, Johnson R, McCracken W: Transcutaneous electrical nerve stimu
lation: Its role in the control of chronic pain. Arch Phys Med Rehabil 65:228-231,1984
10. Goldner JL, Nashold BS Jr, Hendrix PC: Peripheral nerve electrical stimulation. Clin Orthop 163:33-41, 1982
11. Hansson P, Ekblom A: Transcutaneous electrical nerve stimulation (TENS) as compared to placebo TENS for the relief of acute oro-facial pain. Pain 15:157-165,1983
12. Harvie KW: A major advance in the control of postoperative knee pain. Orthopedics 2:1-2, 1979
13. Hiedl P, Struppler A, Gessler M: TENS-evoked long loop effects. Appl Neuro-physiol 42:153-159, 1979
14. Hughes GS Jr, Lichstein PR, Whitlock D, et al: Response of plasma beta-endor-phins to transcutaneous electrical nerve stimulation in healthy subjects. Phys Ther 64:1062-1066,1984
15. Ignelzi RJ, Nyquist JK: Excitability changes in peripheral nerve fibers following repetitive electrical stimulation: Implications in pain modulation. J Neurosurg 51:824-830,1979
16. Janko M, Trontelj JV: Transcutaneous electrical nerve stimulation: A microneu-rographic and perceptual study. Pain 9:219-230, 1980
17. Janko M, Trontelj JV: Flexion withdrawal reflex as recorded from single human biceps femoris motor neurones. Pain 15:167-176,1983
18. Jenkner FL, Schurfried F: Transdermal transcutaneous electric nerve stimulation for pain: The search for an optimal waveform. Appl Neurophysiol 44:330-337, 1981
19. Johansson F, Almay BGL, Von Knorring L, et al: Predictors for the outcome of treatment with high frequency transcutaneous electrical nerve stimulation in patients with chronic pain. Pain 9:55-61, 1980
20. Krueger HC, Wong R, Jette DU: Opinions and comments: Use or misuse of TENS with acupuncture. Phys Ther 64:1574-1576,1984
21. LeBars D, Besson JM: The spinal site of action of morphine in pain relief: From basic research to clinical applications. Trends in Pharmacological Sciences 2:323-325, 1981
22. Lewis JW, Cannon JT, Lieberskind JC: Opioid and nonopioid mechanisms of stress analgesia. Science 208:623-625, 1980
23. Malow RM, Dougher MJ: A signal detection analysis of the effects of transcutaneous stimulation on pain. Psychosom Med 41:101-108, 1979
24. Mannheimer C, Lund S, Carlsson C-A: The effect of transcutaneous electrical nerve stimulation (TENS) on joint pain in patients with rheumatoid arthritis. Scand J Rheumatol 7:13-16, 1978
25. Martin R, Salbaing J, Blaise G, et al: Epidural morphine for postoperative pain relief: A dose-response curve. J Anesthesiology 56:423-426, 1982
26. McCarthy JA, Zigenfus RW: Transcutaneous electrical nerve stimulation: An adjunct in the pain management of Guillain-Barre Syndrome: A case report. Phys Ther 58:23-24,1978
322 PHYSICAL THERAPY
PRACTICE
27. McCreery DB, Bloedel JR: A critical examination of the use of signal detection theory in evaluating a putative analgesic—transcutaneous electrical nerve stimulation. Sensory Processes 2:38-57, 1978
28. Melzack R: Recent concepts of pain. J Med 13:147-160, 1982
29. Melzack R, Vetere P, Finch L: Transcutaneous electrical nerve stimulation for low back pain: A comparison of TENS and massage for pain and range of motion. Phys Ther 63:489-493, 1983
30. Meyer PG, Nashold BS, Peterson J: Diagnosis of electric neurostimulating device dysfunction. Appl Neurophysiol 42:352-364, 1979
31. Millea TP: Transcutaneous electrical nerve stimulation in the management of nonoperative intra-abdominal pain: A case report. Phys Ther 63:1280-1282, 1983
32. Miller Jones CMH: Forum: Transcutaneous nerve stimulation in labour. Anaesthesia 35:372-375, 1980
33. Nielźen S, Sjölund BH, Eriksson MBE: Psychiatric factors influencing the treatment of pain with peripheral conditioning stimulation. Pain 13:365-371, 1982
34. O'Brien WJ, Rutan FM, Sanborn C, et al: Effect of transcutaneous electrical nerve stimulation on human blood β-endorphin levels. Phys Ther 64:1367-1374, 1984
35. Ottoson D, Ekblom A, Hansson P: Vibratory stimulation for the relief of pain of dental origin. Pain 10:37-45, 1981
36. Owens S, Atkinson ER, Lees DE: Thermographic evidence of reduced sympathetic tone with transcutaneous nerve stimulation. Anesthesiology 50:62-65, 1979
37. Paris DL, Baynes F, Gucker B: Effects of the neuroprobe in the treatment of second-degree ankle inversion sprains. Phys Ther 63:35-40, 1983
38. Pesschanski M, Guilbaud G, Gautron M: Posterior intralaminar region in rat: Neuronal responses to noxious and nonnox-ious cutaneous stimuli. Exp Neurol 73:226-238, 1981
39. Pike PMH: Transcutaneous electrical stimulation: Its use in the management of postoperative pain. Anaesthesia 33:165-171, 1978
40. Pomeranz B, Cheng R: Suppression of noxious responses in single neurons of cat spinal cord by electroacupuncture and its reversal by the opiate antagonist naloxone. Exp Neurol 64:327-341, 1979
41. Reynolds AC, Abram SE, Anderson RA, et al: Chronic pain therapy with transcutaneous electrical nerve stimulation: Predictive value of questionnaires. Arch Phys Med Rehabil 64:311-313, 1983
42. Richardson RR, Cerullo LJ: Transabdominal neurostimulation in treatment of neurogenic ileus. Appl Neurophysiol 42:375-382, 1979
43. Richardson RR, Cerullo LJ, Raimondi AJ: Transabdominal neurostimulation in the treatment of neurogenic ileus. Paper read at Fifty-fifth Annual American Congress of Rehabilitation Medicine, New Orleans, LA, November 12, 1978
44. Salar G, Job I: Modification de L'Action Antalgioue de L'Electrotérapie Transcu-tanee Aprés Traitement Avec Naloxone: Note préliminaire. Neurochirurgie 24:415-417,1978
45. Salar G, Job I, Mingrino S, et al: Effect of transcutaneous electrotherapy on CSF beta-endorphin content in patients without pain problems. Pain 10:169-172, 1981
46. Schneider RJ: Low temperature painful stimulus alters brain wave pattern of transcutaneous electrical stimulus. Life Sci 28:1269-1278, 1981
47. Schomburg FL, Carter-Baker SA: Transcutaneous electrical nerve stimulation for postlaparotomy pain. Phys Ther 63:188-193, 1983
48. Sebille A, Bondoux-Jahan M: Effects of electric stimulation and previous nerve injury on motor function recovery in rats. Brain Res 193:562-565, 1980
49. Siegfried J, Haas HL: Inhibition by transcutaneous electrical stimulation of noxious heat elicited in human gasserian ganglion. Eur Neurol 18:353-355, 1979
50. Stanley TH, Cazalaa JA, Atinault A, et al: Transcutaneous cranial electrical stimulation decreases narcotic requirements during neurolept anesthesia and operation in man. Anesth Analg 61:863-866, 1982
51. Stanley TH, Cazalaa JA, Limoge A, et al: Transcutaneous cranial electrical stimulation increases the potency of nitrous oxide in humans. Anesthesiology 57:293-297, 1982
52. Strax TE (Instructor): TENS-clinical applications. Paper read at the Fifty-fifth Annual American Congress of Rehabilitation Medicine, New Orleans, LA, November 14, 1978
53. Talonen P, Malmivuo J, Baer G, et al: Transcutaneous, dual channel phrenic nerve stimulator for diaphragm pacing. Med Biol Eng Comput 21:21-30, 1983
54. Taylor P, Hallett M, Flaherty L: Treatment of osteoarthritis of the knee with transcutaneous electrical nerve stimulation. Pain 11:233-240, 1981
55. Trief PM: Chronic back pain: Tripartite model of outcome. Arch Phys Med Rehabil 64:53-56, 1983
56. Urban BJ, Nashold BS: Combined epidural and peripheral nerve stimulation for relief of pain. J Neurosurg 57:365-369, 1982
57. Wilier JC, Roby A, Boulu P, et al: Depressive effect of high frequency peripheral conditioning stimulation upon the nociceptive component of the human blink reflex: Lack of naloxone effect. Brain Res 239:322-326, 1982
58. Wilier JC, Roby A, Boulu P, et al: Comparative effects of electroacupuncture and transcutaneous nerve stimulation on the human blink reflex. Pain 14:267-278, 1982
59. Wolf SL, Gersh MR, Rao VR: Examination of electrode placements and stimulating parameters in treating chronic pain with conventional transcutaneous electrical nerve stimulation (TENS). Pain 11:37-47,1981
60. Wong RA, Jette DU: Changes in sympathetic tone associated with different forms of transcutaneous electrical stimulation in healthy subjects. Phys Ther 64:478-482, 1984
61. Woolf CJ: Transcutaneous electrical nerve stimulation and the reaction to experimental pain in human subjects. Pain 7:115-127,1979
62. Woolf CJ, Barrett GD, Mitchell D, et al: Naloxone-reversible peripheral electroanalgesia in intact and spinal rats. Eur J Pharmacol 45:311-314,1977
63. Wynne J, Parry L: Transcutaneous nerve stimulation—an experimental study of its analgesic action. Acupunct Elec-trother Res 4:195-202, 1979
64. Zoppi M, Francini F, Maresca C, et al: Changes of cutaneous sensory thresholds induced by non-painful transcutaneous electrical nerve stimulation in normal subjects and in subjects with chronic pain. J Neurol Neurosurg Psychiatry 44:708-717,1981
PAIN: MECHANISM
A. Clinical 1. Abram SE, Anderson RA: Using a pain
questionnaire to predict response to steroid epidurals. Reg Anaesth 5:11-14,1980
2. Abram SE, Anderson RA, Maitra-D'Cruze AM: Factors predicting short-term outcome of nerve blocks in the management of chronic pain. Pain 10:323-330,1981
3. Amano K, Tanikawa T, Kawamura H, et al: Endorphins and pain relief—further observations on electrical stimulation of the lateral part of the periaqueductal gray matter during rostral mesencephalic reticulotomy for pain relief. Appl Neurophysiol 45:123-135, 1982
4. Besson JM, Guilbaud G, Abdelmou-mene M, et al: Physiologie de la nociception. J Physiol (Paris) 78:7-107, 1982
5. Boivie J, Meyerson BA: A correlative anatomical and clinical study of pain suppression by deep brain stimulation. Pain 13:113-126, 1982
6. Brucini M, Duranti R, Galletti R, et al: Pain thresholds and electromyographic features of periarticular muscles in patients with osteoarthritis of the knee. Pain 10:57-66, 1981
7. Campbell JN: Examination of possible mechanisms by which stimulation of the spinal cord in man relieves pain. Appl Neurophysiol 44:181-186,1981
8. Chao EYS: Justification of triaxial goniometer for the measurement of joint rotation. J Biomech 13:989-1006, 1980
9. Clum GA, Luscumb RL, Scott L: Relaxation training and cognitive redirection strategies in the treatment of acute pain. Pain 12:175-183, 1982
10. Condes- Lara M, Calvo JM, Fernandez-Guardiola A: Habituation to bearable experimental pain elicited by tooth pulp electrical stimulation. Pain 11:185-200, 1981
Volume 65 / Number 3, March 1985 323
11. Cram JR, Stegar JC: EMG scanning in the diagnosis of chronic pain. Biofeedback Self Regul 8:229-241, 1983
12. Doleys DM, Crocker M, Patton D: Response of patients with chronic pain to exercise quotas. Phys Ther 62:1111-1114,1982
13. Dowling J: Autonomic indices and reactive pain reports on the McGill Pain Questionnaire. Pain 14:387-392, 1982
14. Duranti R, Galletti R, Pantaleo T: Relationships between characteristics of electrical stimulation, muscle pain and blink responses in man. Electroence-phalogr Clin Neurophysiol 55:637-644, 1983
15. Gehrig JD, Colpitts YH, Chapman CR: Effects of local anesthetic infiltration on brain potentials evoked by painful dental stimulation. Anesth Analg 60:779-782, 1981
16. Gregg JM, Banerjee T, Ghia JN, et al: Radiofrequency thermoneurolysis of peripheral nerves for control of trigeminal neuralgia. Pain 5:231-243, 1978
17. Hiedl P, Struppler A, Gessler M: Local analgesia by percutaneous electrical stimulation of sensory nerves. Pain 7:129-134,1979
18. Hosobuchi Y: The majority of unmyelinated afferent axons in human ventral roots probably conduct pain. Pain 8:167-180,1980
19. Howe JF: Phantom limb pain—a re-afferentation syndrome. Pain 15:101-107, 1983
20. Kaplan RM, Metzger G, Jablecki C: Brief cognitive and relaxation training increases tolerance for a painful clinical electromyographic examination. Psy-chosom Med 45:155-162, 1983
21. King RB: Principles of pain management: A short review. J Neurosurg 50:554-559, 1979
22. Krivoy WA, Couch JR, Stewart JM, et al: Modulation of cat monosynaptic reflexes by substance P. Brain Res 202:365-372, 1980
23. Laemle LK: Neuronal populations of the human periaqueductal gray, nucleus lateralis. J Comp Neurol 186:93-107, 1979
24. Laitinen LV: Inhibition of cutaneous nociception by deep musculoskeletal pain: A clinical observation. Pain 13:373-377, 1982
25. Levine JD, Gordon NC, Fields HL: Naloxone dose dependently produces analgesia and hyperalgesia in postoperative pain. Nature 278:740-741, 1979
26. Levine JD, Gordon NC, Smith R, et al: Post-operative pain: Effect of extent of injury and attention. Brain Res 234:500-504, 1982
27. Levine JD, Lane ST, Gordon NC, et al: A spinal opioid synapse mediates the interaction of spinal and brain stem sites in morphine analgesia. Brain Res 236:85-91,1982
28. Lindblom U, Tegner R: Are the endorphins active in clinical pain states? Narcotic antagonism in chronic pain patients. Pain 7:65-68, 1979
29. Long DM, Erickson D, Campbell J, et al: Electrical stimulation of the spinal cord and peripheral nerves for pain con
trol. Appl Neurophysiol 44:207-217, 1981
30. Malow RM, Olson RE: Changes in pain perception after treatment for chronic pain. Pain 11:65-72, 1981
31. Markoff RA, Ryan P, Young T: Endorphins and mood changes in long-distance running. Med Sci Sports Exerc 14:11-15,1982
32. Marsland AR, Weekes JWN, Atkinson RL, et al: Phantom limb pain: A case for beta blockers? Pain 12:295-297, 1982
33. Mather L, Mackie J: The incidence of postoperative pain in children. Pain 15:271-282,1983
34. Meglio M, Cioni B, Del Lago A, et al: Pain control and improvement of peripheral blood flow following epidural spinal cord stimulation. J Neurosurg 54:821-823, 1981
35. Melzack R, Loeser JD: Phantom body pain in paraplegics: Evidence for a central "Pattern Generating Mechanism" for pain. Pain 4:195-210, 1978
36. Meyer RA, Campbell JN: Myelinated nociceptive afferents account for the hyperalgesia that follows a burn to the hand. Science 213:1527-1529, 1981
37. Mills KR, Newham DJ, Edwards RHT: Force, contraction frequency and energy metabolism as determinants of is-chaemic muscle pain. Pain 14:149-154, 1982
38. Neumann PB, Henriksen H, Grosman N, et al: Plasma morphine concentrations during chronic oral administration in patients with cancer pain. Pain 13:247-252, 1982
39. Noordenbos W, Wall PD: Implications of the failure of nerve resection and graft to cure chronic pain produced by nerve lesions. J Neurol Neurosurg Psychiatry 44:1068-1073, 1981
40. Pertovaara A, Kemppainen P, Johansson G, et al: Ischemic pain nonsegmen-tally produces a predominant reduction of pain and thermal sensitivity in man: A selective role for endogenous opioids. Brain Res 251:83-92, 1982
41. Pertovaara A: Modification of human pain threshold by specific tactile receptors. Acta Physiol Scand 107:339-341, 1979
42. Ray CD: Spinal epidural electrical stimulation for pain control: Practical details and results. Appl Neurophysiol 44:194-206, 1981
43. Ready LB, Sarkis E, Turner JA: Self-reported vs actual use of medications in chronic pain patients. Pain 12:285-294, 1982
44. Richelson E: Spinal opiate administration for chronic pain: A major advance in therapy. Mayo Clin Proc 56:1-3, 1981
45. Roby A, Bussel B, Wilier JC: Morphine reinforces post-discharge inhibition of a-motoneurons in man. Brain Res 222:209-212, 1981
46. Rosenfeld JP, Pickrel C, Bronton JG: Analgesia for orofacial nociception produced by morphine microinjection into the spinal trigeminal complex. Pain 15:145-155, 1983
47. Salter M, Brooke RI, Merskey H, et al: Is the temporo-mandibular pain and dysfunction syndrome a disorder of the mind? Pain 17:151-166, 1983
48. Schull J, Kaplan H: Naloxone can alter experimental pain and mood in humans. Physiological Psychology 9:245-250, 1981
49. Scott DS, Gregg JM: Myofascial pain of the temporo-mandibular joint: A review of the behavioral-relaxation therapies. Pain 9:231-241, 1980
50. Simone DA, Bodnar RJ: Modulation of antinociceptive responses following tail pinch stress. Life Sci 30:719-729, 1982
51. Speculand B, Goss AN, Hughes A, et al: Temporo-mandibular joint dysfunction: Pain and illness behavior. Pain 17:139-150,1983
52. Turner JA, Calsyn DA, Fordyce WE, et al: Drug utilization patterns in chronic pain patients. Pain 12:357-363, 1982
53. Varni JW: Self-regulation techniques in the management of chronic arthritic pain in hemophilia. Behavior Therapy 12:185-194, 1981
54. Varni JW: Behavioral medicine in hemophilia arthritic pain management: Two case studies. Arch Phys Med Rehabil 62:183-187, 1981
55. Varni JW, Bessman CA, Russo DC, et al: Behavioral management of chronic pain in children: Case study. Arch Phys Med Rehabil 61:375-379, 1980
56. Wilier JC, Albe-Fessard D: Further studies on the role of afferent input from relatively large diameter fibers in transmission of nociceptive messages in humans. Brain Res 278:318-321, 1983
57. Wilier JC, Boureau F, Albe-Fessard D: Human nociceptive reactions of spatial summation of afferent input from relatively large diameter fibers. Brain Res 201:465-470, 1980
58. Wilier JC, Boureau F, Albe-Fessard D: Supraspinal influences on nociceptive flexion reflex and pain sensation in man. Brain Res 179:61-68, 1979
59. Wolf SL: Perspectives on central nervous system responsiveness to transcutaneous electrical nerve stimulation. Phys Ther 58:1443-1449, 1978
60. Woolf CJ: Evidence for a central component of post-injury pain hypersensitivity. Nature 306:686-688, 1983
PAIN: MECHANISM
B. Basic 1. Abbott FV, Melzack R, Samuel C: Mor
phine analgesia in the tail-flick and formalin pain tests is mediated by different neural systems. Exp Neurol 75:644-651,1982
2. Abols IA, Basbaum AI: Afferent connections of the rostral medulla of the cat: A neural substrate for midbrain-medul-lary interactions in the modulation of pain. J Comp Neurol 201:285-297, 1981
3. Andersen E, Nachum D: An ascending serotonergic pain modulation pathway from the dorsal raphe nucleus to the
324 PHYSICAL THERAPY
PRACTICE
parafasciculans nucleus of the thalamus. Brain Res 269:57-67, 1983
4. Andersen RK, Lund JP, Puil E: Excitation and inhibition of neurons in the trigeminal nucleus caudalis following periaqueductal gray stimulation. Can J Physiol Pharmacol 56:157-161, 1978
5. Azami J, Llewelyn MB, Roberts MHT: The contribution of nucleus reticularis paragigantocellularis and nucleus raphe magnus to the analgesia produced by systemically administered morphine, investigated with the microinjection technique. Pain 12:229-246, 1982
6. Basbaum Al, Clanton CH, Fields HL: Three bulbospinal pathways from the rostral medulla of the cat: An autoradiographic study of pain modulating systems. J Comp Neurol 178:209-224, 1978
7. Basbaum Al, Fields HL: Endogenous pain control mechanisms: Review and hypothesis. Ann Neurol 4:451-462, 1978
8. Beal JA, Bicknell HR: Primary afferent distribution pattern in the marginal zone (Lamina I) of adult monkey and cat lumbosacral spinal cord. J Compar Neurol 202:255-263, 1981
9. Beal JA, Penny JE, Bicknell HR: Structural diversity of marginal (Lamina I) neurons in the adult monkey (Macaca mulatta) lumbosacral spinal cord: A Golgi study. J Compar Neurol 202:237-254, 1981
10. Behbehani MM, Fields HL: Evidence that an excitatory connection between the periaqueductal gray and nucleus raphe magnus mediates stimulation produced analgesia. Brain Res 170:85-93,1979
11. Behbehani MM, Pomeroy SL: Effect of morphine injected in periaqueductal gray on the activity of single units in nucleus raphe magnus of the rat. Brain Res 149:266-269, 1978
12. Benabid AL, Henriken SJ, McGinty JF, et al: Thalamic nucleus ventro-postero-lateralis inhibits nucleus parafasciculans response to noxious stimuli through a non-opioid pathway. Brain Res 280:217-231, 1983
13. Bennett GJ, Mayer DJ: Inhibition of spinal cord interneurons by narcotic microinjection and focal electrical stimulation in the periaqueductal central gray matter. Brain Res 172:243-257, 1979
14. Biedenbach MA, Van Hassel HJ, Brown AC: Tooth pulp-driven neurons in somatosensory cortex of primates: Role in pain mechanisms including a review of the literature. Pain 7:31-50, 1979
15. Brinkhus HB, Carstens E, Zimmermann M: Encoding of graded noxious skin heating by neurons in posterior thalamus and adjacent areas in the cat. Neu-rosci Lett 15:37-42, 1979
16. Brinkhus HB, Zimmermann M: Characteristics of spinal dorsal horn neurons after partial chronic deafferenta-tion by dorsal root transection. Pain 15:221-236, 1983
17. Brushart TM, Henry EW, Mesulam M-M: Reorganization of muscle afferent projections accompanies peripheral
nerve regeneration. Neuroscience 6:2053-2061,1981
18. Burgoin S, Oliveras JL, Bruxelle J, et al: Electrical stimulation of the nucleus raphe magnus in the rat. Effects on 5-HT metabolism in the spinal cord. Brain Res 194:377-389, 1980
19. Cannon JT, Lewis JW, Weinberg VE, et al: Evidence for the independence of brainstem mechanisms mediating analgesia induced by morphine and two forms of stress. Brain Res 269:231-236, 1983
20. Cannon JT, Prieto GJ, Lee A, et al: Evidence for opioid and non-opioid forms of stimulation-produced analgesia in the rat. Brain Res 243:315-321, 1982
21. Carstens E: Inhibition of spinal dorsal horn neuronal responses to noxious skin heating by medial hypothalamic stimulation in the cat. J Neurophysiol 48:808-822, 1982
22. Carstens E, Fraunhoffer M, Suberg SN: Inhibition of spinal dorsal horn neuronal responses to noxious skin heating by lateral hypothalamic stimulation in the cat. J Neurophysiol 50:192-204, 1983
23. Carstens E, Fraunhoffer M, Zimmermann M: Serotonergic mediation of descending inhibition from midbrain periaqueductal gray, but not reticular formation, of spinal nociceptive transmission in the cat. Pain 10:149-167, 1981
24. Carstens E, Klumpp D, Zimmermann M: Differential inhibitory effects of medial and lateral midbrain stimulation on spinal neuronal discharges to noxious skin heating in the cat. J Neurophysiol 43:332-342, 1980
25. Carstens E, Klumpp D, Zimmermann M: The opiate antagonist, naloxone, does not affect descending inhibition from midbrain of nociceptive spinal neuronal discharges in the cat. Neurosci Lett 11:323-327, 1979
26. Carstens E, Klumpp D, Zimmermann M: Time course and effective sites for inhibition from midbrain periaqueductal gray of spinal dorsal horn neuronal responses to cutaneous stimuli in the cat. Exp Brain Res 38:425-430, 1980
27. Carstens E, Yokota T, Zimmermann M: Inhibition of spinal neuronal responses to noxious skin heating by stimulation of mesencephalic periaqueductal gray in the cat. J Neurophysiol 42:558-568, 1979
28. Carstens E, Zimmermann M: The opiate antagonist naloxone does not consistently block inhibition of spinal nociceptive transmission produced by stimulation in lateral midbrain reticular formation of the cat. Neurosci Lett 20:335-339, 1980
29. Casey KL, Morrow TJ: Ventral posterior thalamic neurons differentially responsive to noxious stimulation of the awake monkey. Science 221:675-677, 1983
30. Cervero F, Iggo A, Molony V: An electrophysiological study of neurones in the substantia gelatinosa rolandi of the cat's spinal cord. J Exp Physiol 64:297-314, 1979
31. Cervero F, Iggo A, Molony V: Segmental and intersegmental organization of neurones in the substantia gelatinosa rolandi of the cat's spinal cord. J Exp Physiol 64:315-326, 1979
32. Cervero F, Molony V, Iggo A: Supraspinal linkage of substantia gelatinosa neurones: Effects of descending impulses. Brain Res 175:351-355, 1979
33. Chan SHH: Central neurotransmitter systems in the morphine suppression of jaw-opening reflex in rabbits: The dopaminergic system. Exp Neurol 65:526-534, 1979
34. Chan SHH, Lai Y-Y: Effects of aging on pain responses and analgesic efficacy of morphine and clonidine in rats. Exp Neurol 75:112-119, 1982
35. Cheh G, Sykova E, Vyklicky L: Neurones activated from nociceptors in the spinal cord of the frog. Neurosci Lett 16:257-262, 1980
36. Colpaert FC, Niemegeers CJE, Jans-sen PA: Nociceptive stimulation prevents development of tolerance to narcotic analgesia. Eur J Pharmacol 49:335-336, 1978
37. Dennis SG, Choiniere M, Melzack R: Stimulation-produced analgesia in rats: Assessment by two pain tests and correlation with self-stimulation. Exp Neurol 68:295-309, 1980
38. Devor M, Govrin-Lippmann R: Axo-plasmic transport block reduces ectopic impulse generation in injured peripheral nerves. Pain 16:73-85, 1983
39. Devor M, Wall PD: Plasticity in the spinal cord sensory map following peripheral nerve injury in rats. J Neurosci 1:679-684,1981
40. Dickenson AH: The inhibitory effects of thalamic stimulation on the spinal transmission of nociceptive information in the rat. Pain 17:213-224, 1983
41. Dickenson AH, Oliveras JL, Besson JM: Role of the nucleus raphe magnus in opiate analgesia as studied by the microinjection technique in the rat. Brain Res 170:95-111, 1979
42. Dickenson AH, Rivot JP, Chaouch A, et al: Diffuse noxious inhibitory controls (DNIC) in the rat with or without pCPA pretreatment. Brain Res 216:313-321, 1981
43. Dohi S, Toyooka H, Kitahata LM: Effects of morphine sulfate on dorsal-horn neuronal responses to graded noxious thermal stimulation in the decerebrate cat. Anesthesiology 51:408-413,1979
44. Dong WK, Ryu H, Wagman IH: Nociceptive responses of neurons in medial thalamus and their relationship to spinothalamic pathways. J Neurophysiol 41:1592-1613.1978
45. Dostrovsky JO: Raphe and peraque-ductal gray induced suppression of non-nociceptive neuronal responses in the dorsal column nuclei and trigeminal sub-nucleus caudalis. Brain Res 200:184-189,1980
46. Dostrovsky JO, Shah Y, Gray BG: Descending inhibitory influences from periaqueductal gray, nucleus raphe magnus, and adjacent reticular formation.
Volume 65 / Number 3, March 1985 325
II. Effects on medullary dorsal horn nociceptive and nonnociceptive neurons. J Neurophysiology 49:948-960, 1983
47. Dubner R, Bennett GJ: Spinal and trigeminal mechanisms of nociception. Ann Rev Neurosci 6:381-418, 1983
48. Dubuisson D, Wall PD: Medullary raphe influences on units in laminae 1 and 2 of cat spinal cord. J Physiol (Paris) 300:33, 1979
49. Edmeads J: The physiology of pain: A review. Neuropsychopharmacology and Biological Psychiatry 7:413-419, 1983
50. Emmers R: Dual alterations of thalamic nociceptive activity by stimulation on the periaqueductal gray matter. Exp Neurol 65:186-201, 1979
51. Fields HL, Anderson SD: Evidence that raphe-spinal neurons mediate opiate and midbrain stimulation-produced analgesias. Pain 5:333-349, 1978
52. Fields HL, Basbaum Al: Brainstem control of spinal pain-transmission neurons. Annu Rev Physiol 40:217-248, 1978
53. Fitzgerald M, Wall PD: The laminar organization of dorsal horn cells responding to peripheral C-fibre stimulation. Exp Brain Res 41:36-44, 1980
54. Fitzgerald M, Woolf CJ: Differential laminar response of dorsal horn neurones to naloxone in the spinal rat. J Physiol (Lond) 305:98, 1980
55. Fox JE, Wolstencroft JH: The reduced responsiveness of neurones in nucleus reticularis gigantocellularis following their excitation by peripheral nerve stimulation. J Physiol (Lond) 258:687-704, 1976
56. Gebhart GF: Opiate and opioid peptide effects on brain stem neurons: Relevance to nociception and antinociceptive mechanisms. Pain 12:93-140, 1982
57. Gebhart GF, Toleikis JR: An evaluation of stimulation-produced analgesia in the cat. Exp Neurol 626:570-679, 1978
58. Gebhart GF, Sandkuhler J, Thalham-mer JG, et al: Inhibition of spinal nociceptive information by stimulation in midbrain of the cat is blocked by lido-caine microinjected in nucleus raphe magnus and medullary reticular formation. J Neurophysiol 50:1446-1459, 1983
59. Gerhart KD, Wilcox TK, Chung JM, et al: Inhibition of nociceptive and nonnociceptive responses of primate spinothalamic cells by stimulation in medial brain stem. J Neurophysiol 45:121-136, 1981
60. Gerhart KD, Yezierski RP, Fang ZR, et al: Inhibition of primate spinothalamic tract neurons by stimulation in ventral posterior lateral (VP1c) thalamic nucleus: Possible mechanisms. J Neurophysiol 49:406-423, 1983
61. Gerhart KD, Yezierski RP, Wilcox TK, et al: Inhibition of primate spinothalamic tract neurons by stimulation in periaqueductal gray or adjacent midbrain reticular formation. J Neurophysiol 51:450-466, 1984
62. Giesler GJ, Menetrey D, Basbaum AI: Differential origins of spinothalamic tract projections to medial and lateral thalamus in the rat. J Comp Neurol 184:107-125, 1979
63. Gray BG, Dostrovsky JO: Descending inhibitory influences from periaqueductal gray, nucleus raphe magnus, and adjacent reticular formation. I. Effects on lumbar spinal cord nociceptive and nonnociceptive neurons. J Neurophysiol 49:943-947, 1983
64. Haber LH, Martin RF, Chung JM, et al: Inhibition and excitation of primate spinothalamic tract neurons by stimulation in region of nucleus reticularis gigantocellularis. J Neurophysiol 43:1578-1593,1980
65. Haber LH, Moore BD, Willis WD: Electrophysiological response properties of spinoreticular neurons in the monkey. J Comp Neurol 207:75-84, 1982
66. Hammond DL, Proudfit HK: Effects of locus coeruleus lesions on morphine-induced antinociception. Brain Res
- 188:79-91, 1980 67. Hanaoka K, Ohtani M, Toyooka H, et
al: The relative contribution of direct and supraspinal descending effects upon spinal mechanisms of morphine analgesia. J Pharmacol Exp Ther 207:476-484, 1978
68. Hardy SGP, Haigler HJ, Leichnetz GR: Paralemniscal reticular formation: Response of cells to a noxious stimulus. Brain Res 267:217-223, 1983
69. Hayes RL, Bennett GJ, Newlon PG, et al: Behavioral and physiological studies of non-narcotic analgesia in the rat elicited by certain environmental stimuli. Brain Res 155:69-90, 1978
70. Hayes RL, Price DD, Ruda M, et al: Suppression of nociceptive responses in the primate by electrical stimulation of the brain or morphine administration: Behavioral and electrophysiological comparisons. Brain Res 167:417-421, 1979
71. Heinricher MM, Rosenfeld P: Microinjection of morphine into nucleus reticularis paragigantocellularis of the rat suppresses spontaneous activity of nucleus raphe magnus neurons. Brain Res 272:382-386, 1983
72. Hentall ID, Fields HL: Potentiation of transmission from C-fibers to dorsal horn neurons after tetanus of peripheral nerve. Brain Res 189:540-543, 1980
73. Hentall ID, Fields HL: Segmental and descending influences on intraspinal thresholds of single C-fibers. J Neurophysiol 42:1527-1537, 1979
74. Hill RG, Morris R: Responses of nucleus reticularis ventralis neurones of the rat to noxious stimuli and to elec-trical stimulation of the periaqueductal gray and raphe dorsalis. J Physiol (Lond) 301:38-39, 1979
75. Honda CN, Mense S, Perl ER: Neurons in ventrobasal region of cat thalamus selectively responsive to noxious mechanical stimulation. J Neurophysiol 49:662-673, 1983
76. Iggo A: Peripheral and spinal "pain" mechanisms and their modulation. Ad
vances in Pain Research and Therapy 1:381-394,1976
77. Jordan LM, Kenshalo DR, Martin RF, et al: Two populations of spinothalamic tract neurons with opposite responses to 5-hydroxytryptamine. Brain Res 164:342-346, 1979
78. Jurna I: Effect of stimulation in the periaqueductal gray matter on activity in ascending axons of the rat spinal cord: Selective inhibition of activity evoked by afferent A-delta and C-fibre stimulation and failure of naloxone to reduce inhibition. Brain Res 196:33-42, 1980
79. Keith CK, Ebner TJ, Bloedel JR: Effects of periaqueductal gray and raphe magnus stimulation on the responses of spinocervical, and other ascending projection neurons to non-noxious inputs. Brain Res 291:29-37, 1984
80. Kerr FWL, Wilson PR: Pain. Annu Rev Neurosci 1:83-102,1978
81. KrausE, Besson JM, LeBars D: Behavioral model for diffuse noxious inhibitory controls (DNIC): Potentiation by 5-hy-droxytryptophan. Brain Res 231:461-465, 1982
82. Kraus E, LeBars D, Besson JM: Behavioral confirmation of "Diffuse Noxious Inhibitory Controls" (DNIC) and evidence for a role of endogenous opiates. Brain Res 206:495-499, 1981
83. Kumazawa T, Perl ER: Excitation of marginal and substantia gelatinosa neurons in the primate spinal cord: Indications of their place in dorsal horn functional organization. J Comp Neurol 177:417-434, 1978
84. LaMotte RH: Information processing in cutaneous nociceptors in relation to sensations of pain. Fed Proc 42;2548-2552, 1983
85. LeBars D, Chitour D, Clot AM: The encoding of thermal stimuli by diffuse noxious inhibitory controls (DNIC). Brain Res 230:394-399, 1981
86. LeBars D, Dickenson AH, Besson JM: Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain 6:283-304, 1979
87. LeBars D, Dickenson AH, Besson JM: Diffuse noxious inhibitory controls (DNIC). II. Lack of effect on non-convergent neurones, supraspinal involvement and theoretical implications. Pain 6:305-327, 1979
88. LeBars D, Dickenson AH, Besson JM: Microinjection of morphine within nucleus raphe magnus and dorsal horn neurone activities related to nociception in the rat. Brain Res 189:467-481, 1980
89. LeBars D, Guilbaud G, Chitour D, et al: Does systemic morphine increase descending inhibitory contrpls of dorsal horn neurones involved in nociception? Brain Res 202:223-228, 1980
90. Levine JD, Gordon NC, Fields HL: Naloxone fails to antagonize nitrous oxide analgesia for clinical pain. Pain 13:165-170, 1982
91. Levitt M: The bilaterally symmetrical deafferentation syndrome in macaques after bilateral spinal lesions: Evidence
326 PHYSICAL THERAPY
PRACTICE
for dysesthesias resulting from brain foci and considerations of spinal pain pathways. Pain 16:167-184, 1983
92. Lewis JW, Terman GW, Watkins LR, et al: Opioid and non-opioid mechanisms of footshock-induced analgesia: Role of the spinal dorsolateral funiculus. Brain Res 267:139-144, 1983
93. Liu RPC: Laminar origins of spinal projection neurons to the periaqueductal gray of the rat. Brain Res 264:118-122,1983
94. Lovick TA, Wolstencroft JH: Responses of medial reticular neurones to tooth pulp stimulation: Evidence for a monosynaptic input. J Physiol (Lond) 292:40-41,1979
95. Maciewicz R, Sandrew BB, Phipps BS, et al: Pontomedullary raphe neurons: Intracellular responses to central and peripheral electrical stimulation. Brain Res 293:17-33, 1984
96. Matsumiya T, Berry JN, Bell JA: The effect of intraspinal microinjection of dopamine on the C-fiber reflex in the acute decerebrate spinal cat. Life Sci 1153-1158, 1979
97. McMahon SB, Wall PD: A system of rat spinal cord lamina 1 cells projecting through the contralateral dorsolateral funiculus. J Comp Neurol 214:217-223, 1983
98. Menetrey D, Chaouch A, Besson JM: Responses of spinal cord dorsal horn neurones to non-noxious and noxious cutaneous temperature changes in the spinal rat. Pain 6:265-282, 1979
99. Meyer RA, Campbell JN: Evidence for two distinct classes of unmyelinated nociceptive afferents in monkey. Brain Res 224:149-152, 1981
100. Milne RJ, Foreman RD, Willis WD: Responses of primate spinothalamic neurons located in the sacral intermedi-omedial gray (Stilling's Nucleus) to proprioceptive input from the tail. Brain Res 234:227-236, 1982
101. Miyakawa H, Okuda K, Shima K, et al: Nociceptive and non-nociceptive responses of neurons in the medial subthalamic region and lateral hypothalamic area of cats and their relationship to the effects of morphine and pentazocine. Tohoku J Exp Med 137:11-19, 1982
102. Mohrland JS, Gebhart GF: Effects of focal electrical stimulation and morphine microinjection in the periaqueductal gray of the rat mesencephalon on neuronal activity in the medullary reticular formation. Brain Res 201:23-37,1980
103. Mohrland JS, McManus DQ, Gebhart GF: Lesions in nucleus reticularis gigan-tocellularis: Effect on the antinocicep-tion produced by microinjection of morphine and focal electrical stimulation in the periaqueductal gray matter. Brain Res 231:143-152, 1982
104. Nakahama H, Shima K, Aya K, et al: Peripheral somatic activation and spontaneous firing patterns of neurons in the periaqueductal gray of the cat. Neu-rosci Lett 25:43-46, 1981
105. Nakahama H, Shima K, Aya K, et al: Antionociceptive action of morphine
and pentazocine on unit activity in the nucleus centralis lateralis, nucleus ven-tralis lateralis and nearby structures of the cat. Pain 10:47-56, 1981
106. Necker R, Hellon RF: Noxious thermal input from the rat tail: Modulation by descending inhibitory influences. Pain 4:231-242, 1978
107. Oleson TD, Kirkpatrick DB, Goodman SJ: Elevation of pain threshold to tooth shock by brain stimulation in primates. Brain Res 194:79-95, 1980
108. Oleson TD, Twombly DA, Liebeskind JC: Effects of pain-attenuating brain stimulation and morphine on electrical activity in the raphe nuclei of the awake cat. Pain 4:211-230, 1978
109. Oliveras JL, Hosobuchi Y, Guilbaud G, et al: Analgesic electrical stimulation of the feline nucleus raphe magnus: Development of tolerance and its reversal by 5-HTP. Brain Res 146:404-409, 1978
110. Olpe H-R: The cortical projection of the dorsal raphe nucleus: Some electrophysiological and pharmacological properties. Brain Res 216:61-71, 1981
111. Peschanski M, Guilbaud G, Gautron M: Neuronal responses to cutaneous electrical and noxious mechanical stimuli in the nucleus reticularis thalami of the rat. Neurosci Lett 20:165-170, 1980
112. Pomeroy SL, Behbehani MM: Physiologic evidence for a projection from periaqueductal gray to nucleus raphe magnus in the rat. Brain Res 176:143-147, 1979
113. Prieto GJ, Cannon JT, Liebeskind JC: N. raphe magnus lesions disrupt stimulation-produced analgesia from ventral but not dorsal midbrain areas in the rat. Brain Res 261:53-57, 1983
114. Proudfit HK: Reversible inactivation of raphe magnus neurons: Effects on nociceptive threshold and morphine-induced analgesia. Brain Res 201:459-464, 1980
115. Rhodes DL: Periventricular system lesions and stimulation-produced analgesia. Pain 7:51-63, 1979
116. Rhodes DL, Liebeskind JC: Analgesia from rostral brain stem stimulation in the rat. Brain Res 143:521-532,1978
117. Rivot JP, Chiang CY, Besson JM: Increase of serotonin metabolism within the dorsal horn of the spinal cord during nucleus raphe magnus stimulation, as revealed by in vivo electrochemical detection. Brain Res 238:117-126, 1982
118. Rosenfeld JP, Holzman BS: Effects of morphine on medial thalamic and medial bulboreticular aversive stimulation thresholds. Brain Res 150:436-440, 1978
119. Rosenfeld JP, Stocco S: Differential effects of systemic versus intracranial injection of opiates on central, orofacial and lower body nociception: Somato-typy in bulbar analgesia systems. Pain 9:307-318, 1980
120. Sagen J, Proudfit HK: Hypoalgesia induced by blockade of noradrenergic projections to the raphe magnus: Reversal by blockade of noradrenergic projections to the spinal cord. Brain Res 223:391-396, 1981
121. Salt TE, Hill RG: Pharmacological differentiation between responses of rat medullary dorsal horn neurons to noxious mechanical and noxious thermal cutaneous stimuli. Brain Res 263:167-171, 1983
122. Sanders KH, Klein CE, Mayer TE, et al: Differential effects of noxious and non-noxious input on neurones according to location in ventral periaqueductal grey or dorsal raphe nucleus. Brain Res 186:83-97, 1980
123. Satoh M, Akaike A, Takagi H: Excitation by morphine and enkephalin of single neurons of nucleus reticularis par-agigantocellularis in the rat: A probable mechanism of analgesic action of opioids. Brain Res 169:406-410,1979
124. Segal M: Serotonergic innervation of the locus coeruleus from the dorsal raphe and its action on responses to noxious stimuli. J Physiol (Lond) 286:401-415, 1979
125. Sessle BJ, Hu JW: Raphe-induced suppression of the jaw-opening reflex and single neurons in trigeminal sub-nucleus oralis, and influence of naloxone and subnucleus caudalis. Pain 10:19-36, 1981
126. Shah Y, Dostrovsky JO: Electrophysiological evidence for a projection of the periaqueductal gray matter to nucleus raphe magnus in cat and rat. Brain Res 193:534-538, 1980
127. Sinclair JG, Fox RE, Mokha SS, et al: The effect of naloxone on the inhibition of nociceptor driven neurones in the cat spinal cord. Q J Exp Physiol 65:181-188, 1980
128. Soja PJ, Sinclair JG: The response of dorsal horn neurones of the cat to intraarterial bradykinin and noxious radiant heat. Neurosci Lett 20:183-188,1980
129. Soper WY, Melzack R: Stimulation-produced analgesia: Evidence for soma-totopic organization in the midbrain. Brain Res 251:301-311, 1982
130. Strahlendorf HK, Strahlendorf JC, Barnes CD: Endorphin-mediated inhibition of locus coeruleus neurons. Brain Res 191:284-288, 1980
131. Strahlendorf JC, Strahlendorf HK, Barnes CD: Inhibition of periaqueductal gray neurons by the arcuate nucleus: Partial mediation by an endorphin pathway. Exp Brain Res 46:462-466, 1982
132. Terman GW, Lewis JW, Liebeskind JC: Opioid and non-opioid mechanisms of stress analgesia: Lack of cross-tolerance between stressors. Brain Res 260:147-150, 1983
133. Toyooka H, Kitahata LM, Dohi S, et al: Effects of morphine on the rexed lamina VII spinal neuronal response to graded noxious radiant heat stimulation. Exp Neurol 62:146-158, 1978
134. Trevino DL: Integration of sensory input in laminae I, II and III of the cat's spinal cord. Fed Proc 37:2234-2236, 1978
135. Urea G, Nahin RL, Liebeskind JC: Effects of morphine on spontaneous multiple-unit activity: Possible relation to mechanisms of analgesia and reward. Exp Neurol 66:248-262, 1979
Volume 65 / Number 3, March 1985 327
136. Urca G, Liebeskind JC: Electrophysiological indices of opiate action in awake and anesthetized rats. Brain Res 161:162-166, 1979
137. Vidal C, Jacob J: The effect of medial hypothalamus lesions on pain control. Brain Res 199:89-100, 1980
138. Wall PD, Devor M, inbal R, et al: Auto tomy following peripheral nerve lesions: Experimental anaesthesia dolorosa. Pain 7:103-113, 1979
139. Wang RY, Aghajanian GK: Correlative firing patterns of serotonergic neurons in rat dorsal raphe nucleus. J Neurosci 2:11-16, 1982
140. Warren PH, Ison JR: Selective action of morphine on reflex expression to nociceptive stimulation in the rat: A contribution to the assessment of analgesia. Pharmacol Biochem Behav 16:869-874, 1982
141. Watkins LR, Cobelli DA, Newsome HH, et al: Footshock induced analgesia is dependent neither on pituitary nor sympathetic activation. Brain Res 245:81 -96, 1982
142. Watkins LR, Cobelli DA, Mayer DJ: Opiate vs non-opiate footshock induced analgesia (FSIA) descending and intraspinal components. Brain Res 245:97-106,1982
143. Watkins LR, Drugan R, Hyson RL, et al: Opiate and non-opiate analgesia induced by inescapable tail-shock: Effects of dorsolateral funiculus lesions and decerebration. Brain Res 291:325-336, 1984
144. Watkins LR, Griffin G, Leichnetz GR, et al: Identification and somatotopic organization of nuclei projecting via the dorsolateral funiculus in rats: A retrograde tracing study using HRP slow-release gels. Brain Res 223:237-255, 1981
145. Watkins LR, Griffin G, Leichnetz GR, et al: The somatotopic organization of the nucleus raphe magnus and surrounding brain stem structures as revealed by HRP slow-release gels. Brain Res 181:1-15,1980
146. Watkins LR, Johannessen JN, Kin-scheck IB, et al: The neurochemical basis of footshock analgesia: The role of spinal cord serotonin and norepinephrine. Brain Res 290:107-117, 1984
147. Watkins LR, Kinscheck IB, Mayer DJ: The neural basis of footshock analgesia: The effect of periaqueductal gray lesions and decerebration. Brain Res 276:317-324, 1983
148. Watkins LR, Mayer DJ: Involvement of spinal opioid systems in footshock-in-duced analgesia: Antagonism by naloxone is possible only before induction of analgesia. Brain Res 242:309-316, 1982
149. Watkins LR, Mayer DJ: Organization of endogenous opiate and nonopiate pain control systems. Science 216:1185-1192,1982
150. Watkins LR, Young EG, Kinscheck IB, et al: The neural basis of footshock analgesia: The role of specific ventral medullary nuclei. Brain Res 276:305-315, 1983
151. Weil-Fugazza J, Godefroy F, Coudert D, et al: Morphine analgesia and newly synthesized 5-hydroxytryptamine in the dorsal and the ventral halves of the spinal cord of the rat. Brain Res 214:440-444, 1981
152. Willis WD, Gerhart KD, Willcockson WS, et al: Primate raphe- and reticulospinal neurons effects of stimulation in periaqueductal gray or VPL thalamic nucleus. J Neurophysiol 51:467-480, 1984
153. Willis WD, Kevetter GA: Spinothalamic cells in the rat lumbar cord with collaterals to the medullary reticular formation. Brain Res 238:181-185, 1982
154. Willis WD, Kenshalo DR, Leonard RB, et al: Facilitation of the responses of primate spinothalamic cells to cold and to tactile stimuli by noxious heating of the skin. Pain 12:141-152, 1982
155. Wong CL, Bentley GA: The effect of stress and adrenalectomy on morphine analgesia and naloxone potency in mice. Eur J Pharmacol 56:197-205, 1979
156. Woolf CJ, Wall PD: Chronic peripheral nerve section diminishes the primary afferent A-fibre mediated inhibition of rat dorsal horn neurones. Brain Res 242:77-85, 1982
157. Yezierski RP, Gerhart KD, Schrock BJ, et al: A further examination of effects of cortical stimulation on primate spinothalamic tract cells. J Neurophysiol 49:424-441, 1983
158. Yokota T: Differential inhibitory effects of volleys from dorsal raphe nucleus upon spinal and spino-bulbo-spinal reflexes. Neurosci Lett 7:291-294, 1978
159. Young EG, Watkins LR, Mayer DJ: Comparison of the effects of ventral medullary lesions on systemic and microinjection morphine analgesia. Brain Res 290:119-129, 1984
160. Zamir N, Shuber E: Altered pain perception in hypertensive humans. Brain Res 201:471-474, 1980
161. Zamir N, Simantov R, Segal M: Pain sensitivity and opioid activity in genetically and experimentally hypertensive rats. Brain Res 184:299-310, 1980
162. Zieglgansberger W, Tulloch IF: The effects of methionine- and leucine-enkephalin on spinal neurones of the cat. Brain Res 167:53-64, 1979
163. Zorman G, Hentall ID, Adams JE, et al: Naloxone-reversible analgesia produced by microstimulation in the rat medulla. Brain Res 219:137-148, 1981
PAIN: GENERAL CLINICAL-SURGICAL APPROACHES
1. Amodei N, Paxinos G: Unilateral knife cuts produce ipsilateral suppression of responsiveness to pain in the formalin test. Brain Res 193:85-94, 1980
2. Aronoff GM, Evans WO, Enders PL: A review of follow-up studies of multidisci-plinary pain units. Pain 16:1-11, 1983
3. Badawy AA-B, Evans M, Punjani NF, et al: Does naloxone always act as an opiate antagonist? Life Sci 33:739-742, 1983
4. Carlen PL, Wall PD, Nadvorna H, et al: Phantom limbs and related phenomena in recent traumatic amputation. Neurology 28:211-217, 1978
5. Carstens E, Guinan MJ, MacKinnon JD: Naloxone does not consistently affect inhibition of spinal nociceptive transmission produced by medial diencephalic stimulation in the cat. Neurosci Lett 42:71-76, 1983
6. Chayen MS, Rudick V, Borvine A: Pain control with epidural injection of morphine. Anesthesiology 53:338-339, 1980
7. Cohen FL: Postsurgical pain relief: Patients' status and nurses' medication choices. Pain 9:265-274, 1980
8. Croze S, Duclaux R: Thermal pain in humans: Influence of the rate of stimulation. Brain Res 157:418-421, 1978
9. Devor M: Nerve pathophysiology and mechanisms of pain in causalgia. J Auton Nerv Syst 7:371-384, 1983
10. File SE: Naloxone reduces social and exploratory activity in the rat. Psycho-pharmacology (Berlin) 71:41-44, 1980
11. Gracely RH, Dubner R: Pain assessment in humans—a reply to Hall. Pain 11:109-120, 1981
12. Holden C: Pain, dying, and the health care system. Science 203:984-986, 1979
13. Jacquet YF: Different behavioral effects following intracerebral, intracerebroven-tricular or intraperitoneal injections of naloxone in the rat. Behav Brain Res 1:543-546, 1980
14. Kenton B, Coger R, Crue B, et al: Peripheral fiber correlates to noxious thermal stimulation in humans. Neurosci Lett 17:301-306, 1980
15. MacDonald AJR: Abnormally tender muscle regions and associated painful movements. Pain 8:197-205, 1980
16. Maruyama Y, Shimoji K, Shimizu H, et al: Effects of morphine on human spinal cord and peripheral nervous activities. Pain 8:63-73, 1980
17. Nashold BS, Ostdahl RH: Dorsal root entry zone lesions for pain relief. J Neu-rosurg 51:59-69, 1979
18. Sherman RA, Sherman CJ, Gall NG: A survey of current phantom limb pain treatment in the United States. Pain 8:85-99, 1980
19. Strassburg HM, Thoden U, Mundinger F: Mesencephalic chronic electrodes in pain patients. Appl Neurophysiol 42:284-293, 1979
20. Varni JW, Gilbert A, Dietrich SL: Behavioral medicine in pain and analgesia in management for the hemophilic child with factor VIII inhibitor. Pain 11:121-126, 1981
21. Wahlstrom A, Terenius L: Factor in human CSF with apparent morphine-antagonistic properties. Acta Physiol Scand 110:427-429, 1980
22. Walker JM, Moises HC, Coy DH, et al: Nonopiate effects of dynorphin and des-tyr-dynorphin. Science 218:1136-1138, 1982
23. Watson SJ, Khachaturian H, Akil H, et al: Comparison of the distribution of dynorphin systems and enkephalin sys-
328 PHYSICAL THERAPY
PRACTICE
terns in brain. Science 218:1134-1136, 1982
24. Wilier JC, Bussel B: Evidence for a direct spinal mechanism in morphine-induced inhibition of nociceptive reflexes in humans. Brain Res 187:212-215, 1980
PAIN: ACUPUNCTURE
1. Bragin EO, Vasilenko GF, Durinjan RA: The study of the central grey matter in mechanisms of different kinds of analgesia: Effects of lesions. Pain 16:33-40, 1983
2. Brattberg G: Acupuncture therapy for tennis elbow. Pain 16:285-288, 1983
3. Chapman CR, Colpitts YM, Benedetti C, et al: Evoked potential assessment of acupunctural analgesia: Attempted reversal with naloxone. Pain 9:183-197, 1980
4. Chapman CR, Sato T, Martin RW, et al: Comparative effects of acupuncture in Japan and the United States on dental pain perception. Pain 12:319-328, 1982
5. Cheng RSS, Pomeranz BH: Electroacu-puncture analgesia could be mediated by at least two pain-relieving mechanisms: Endorphin and non-endorphin systems. Life Sci 25:1957-1962, 1979
6. Cheng RSS, Pomeranz BH: Electroacu-puncture analgesia is mediated by ster-eospecific opiate receptors and is reversed by antagonists of type I receptors. Life Sci 26:631-638, 1980
7. Cheng RSS, Pomeranz BH: Monoami-nergic mechanism of electroacupuncture analgesia. Brain Res 215:77-92, 1981
8. Cheng RSS, Pomeranz BH, Yu G: Electroacupuncture treatment of morphine-dependent mice reduces signs of withdrawal, without showing cross-tolerance. Eur J Pharmacol 68:477-481, 1980
9. Crosby WH, Ulett GA: Acupuncture treatments for pain relief. JAMA 245:768-769, 1981
10. Dimitrijevic MR, Faganel J, Young RR: Underlying mechanisms of the effect of spinal cord stimulation in motor disorders. Appl Neurophysiol 44:133-140, 1981
11. Epler DC: Bloodletting in early Chinese medicine and its relation to the origin of acupuncture. Bull Hist Med 54:337-367, 1980
12. Eriksson MBE, Sjolund BH, Nielzen S: Long term results of peripheral conditioning stimulation as an analgesic measure in chronic pain. Pain 6:335-347, 1979
13. Facchinetti F, Nappi G, Savoldi F, et al: Primary headaches: Reduced circulating beta-lipotropin and beta-endorphin levels with impaired reactivity to acupuncture. Cephalalgia 1:195-201, 1981
14. Fu T-C, Halenda SP, Dewey WL: The effect of hypophysectomy on acupuncture analgesia in the mouse. Brain Res 202:33-39, 1980
15. Gwei-Djen L, Needham J: A scientific basis for acupuncture? The Sciences 19:1-10,1979
16. Ha H, Tan E-C, Fukunaga H, et al: Naloxone reversal of acupuncture analgesia in the monkey. Exp Neurol 73:298-303, 1981
17. Ha H, Wu RS, Contreras RA, et al: Measurement of pain threshold stimulation of tooth pulp afferents in the monkey. Exp Neurol 61:260-269, 1978
18. Handelmann GF, Quirion R: Neonatal exposure to morphine increases micro-opiate binding in the adult forebrain. Eur J Pharmacol 94:357-358, 1983
19. Higby D: The nature of pain in patients with cancer—a summary. J Med 13:253-255, 1982
20. Ho WKK, Wen HL, Lam S, et al: The influence of electro-acupuncture on nal-oxone-induced morphine withdrawal in mice: Elevation of brain opiate-like activity. Eur J Pharmacol 49:197-199, 1978
21. Homma I, Motomiya Y: The inhibitory effect of acupuncture on the tonic vibration reflex (TVR) in man. Neurosci Lett 28:315-318, 1982
22. Homma S, Homma I: Inhibitory effect of acupuncture of the vibration-induced grasp reflex in man. Neurosci Lett 32:209-212, 1982
23. Iriki A: Site and action of electroacu-puncture-induced effects on the rat jaw-opening reflex. Exp Neurol 75:36-50, 1982
24. Iriki A, Toda K: Morphine and electroacupuncture: Comparison of the effects on the cortical evoked responses after tooth pulp stimulation in rats. Eur J Pharmacol 68:83-87, 1980
25. Ishiko N, Yamamoto T, Murayama N, et al: Electroacupuncture: Current strength-duration relationship for initiation of hypesthesia in man. Neurosci Lett 8:273-276, 1978
26. Kawakita K: Role of the polymodal receptors in acupuncture analgesia of the rat. Comparative Medicine East and West 6:312-321, 1982
27. Kawakita K, Funakoshi M: Suppression of the jaw-opening reflex by conditioning A-delta fiber stimulation and electroacupuncture in the rat. Exp Neurol 78:461-465, 1982
28. Kerr FWL, Wilson PR, Nijensohn DE: Acupuncture reduces the trigeminal evoked response in decerebrate cats. Exp Neurol 61:84-95, 1978
29. Kline RL, Yeung KY, Calaresu FR: Role of somatic nerves in the cardiovascular responses to stimulation of an acupuncture point in anesthetized rabbits. Exp Neurol 61:561-570, 1978
30. Lamontagne Y, Annable L, Gagnon M-A: Acupuncture for smokers: Lack of long-term therapeutic effect in a controlled study. Can Med Assoc J 122:787-790, 1980
31. Lee MHM, Zaretsky HH, McMeniman M: Acupuncture analgesia-assessment using electric tooth-pulp stimulation: Preliminary report. NY State J Med 78:1687-1690, 1978
32. Lewit K: The needle effect in the relief of myofascial pain. Pain 6:83-90, 1979
33. Lewith GT, Field J, Machin D: Acupuncture compared with placebo in post-her-petic pain. Pain 17:361-368, 1983
34. Lewith GT, Machin D: On the evaluation of the clinical effects of acupuncture. Pain 16:111-127, 1983
35. Lu G-W: Characteristics of afferent fiber innervation on acupuncture points zu-sanli. Am J Physiol 345:606-612, 1983
36. Mao W, Ghia JN, Scott DS, et al: High versus low intensity acupuncture analgesia for treatment of chronic pain: Effects on platelet serotonin. Pain 8:331-342, 1980
37. Melzack R, Katz J: Ariculotherapy fails to relieve chronic pain: A controlled crossover study. JAMA 251:1041 -1043, 1984
38. Monga TN, Jaksic T: Acupuncture in phantom limb pain. Arch Phys Med Re-habil 62:229-231,1981
39. Nappi G, Facchinette F, Bono G, et al: Plasma opioid levels in post-traumatic chronic headache and trigeminal neuralgia: Maintained response to acupuncture. Headache 22:276-279, 1982
40. Nappi G, Facchinetti F, Legnante G, et al: Different releasing effects of traditional manual acupuncture and electroacupuncture on proopiocortin-related peptides. Acupunct Electrother Res 7:93-103, 1982
41. Oleson TD, Kroening RJ, Bresler DE: An experimental evaluation of auricular diagnosis: The somatotopic mapping of musculoskeletal pain at ear acupuncture sets. Pain 8:217-229, 1980
42. Pomeranz B: Do endorphins mediate acupuncture analgesia? In Costa E, Tra-bucci M (eds): Advances in Biochemical Psychopharmacology, New York, NY, Raven Press, 1978, vol 18, pp 351-359
43. Pomeranz B, Paley D: Electroacupuncture hypalgesia is mediated by afferent nerve impulses: An electrophysiological study in mice. Exp Neurol 66:398-402, 1979
44. Pullan PT, Finch PM, Yuen RWM, et al: Endogenous opiates modulate release of growth hormone in response to electroacupuncture. Life Sci 32:1705-1709, 1983
45. Reshetnyak VK, Meizerov EE, Durinyan RA: Changes in functional activity of the large hemispheric cortex and central gray matter in response to electroacupuncture. Research findings from the Central Research Institute of Reflexo-therapy, Moscow, 1982
46. Rico RC, Hobika GH, Avellanosa AM, et al: Use of intrathecal and epidural morphine for pain relief in patients with malignant diseases: A preliminary report. J Med 13:223-231, 1982
47. Rico RC, Trudnowski RJ: Studies with electro-acupuncture. J Med 13:247-251,1982
48. Riscalla LM: Toward establishing scientific credibility in acupuncture research. Med Hypotheses 5:221-224, 1979
49. Sandrew BB, Yang RCC, Wang SC: Electro-acupuncture analgesia in monkeys: A behavioral and neurophysiologi-cal assessment. Arch Int Pharmacodyn Ther 231:274-284, 1978
50. Sarnat HB, Morrissy RT: Idiopathic torticollis: Sternocleidomastoid myopathy and accessory neuropathy. Muscle Nerve 4:374-380, 1981
Volume 65 / Number 3, March 1985 329
PRACTICE
51. Shiner G: Relief from chronic pain: Stimulating the "Morphine Within." Research Resources Reporter 5:1-5, 1981
52. Sodipo JOA: Therapeutic acupuncture for chronic pain. Pain 7:359-365, 1979
53. Toda K: Effects of electro-acupuncture on rat jaw opening reflex elicited by tooth pulp stimulation. Jpn J Physiol 28:485-497, 1978
54. Toda K, Atsushi I, Tanaka H: Electroac-upuncture suppresses the cortical evoked responses in somatosensory I and II areas after tooth pulp stimulation in rat. Jpn J Physiol 30:487-490, 1980
55. Toda K, Ichioka M: Afferent nerve information underlying the effects of elec-troacupuncture in rat. Exp Neurol 65:457-561, 1979
56. Toda K, Ichioka M, Iriki A, et al: Elec-troacupuncture effects on the field potentials in the caudal part of the spinal trigeminal nucleus evoked by tooth pulp stimulation in rat. Exp Neurol 64:704-709, 1979
57. Toda K, Iriki A: Effects of electroacu-puncture on thalamic evoked responses recorded from the ventrobasal complex and posterior nuclear group after tooth pulp stimulation in rat. Exp Neurol 66:419-422, 1979
58. Trudnowski RJ: Current concepts in providing pain relief for cancer patients: Introductory remarks. J Med 13:145, 1982
59. Zhang A, Pan X, Xu S, et al: Endorphins and acupuncture analgesia. Chin Med J [Engl] 93:673-680, 1980
PAIN: NEUROPHARMACOLOGICAL
A. Endogenous Opiates (enkephalins)—Human
1. Akil H, Watson SJ, Sullivan S, et al: Enkephalin-like material in normal human CSF: Measurement and levels. Life Sci 23:121-126, 1978
2. Almay BGL, Johansson F, Von Knorring L, et al: Endorphins in chronic pain. I. Differences in CSF endorphin levels between organic and psychogenic pain syndromes. Pain 5:153-162, 1978
3. Amano K, Kitamura K, Kawamura H, et al: Alterations of immunoreactive beta-endorphin in the third ventricular fluid in response to electrical stimulation of the human periaqueductal gray matter. Appl Neurophysiol 43:150-158, 1980
4. Bjorndal N, Casey DE, Gerfach J: Enkephalin, morphine and naloxone in tardive dyskinesia. Psychopharmacology 69:133-136, 1980
5. Budd K: Psychotropic drugs in the treatment of chronic pain. Anaesthesia 33:531-534, 1978
6. Carr DB, Bullen BA, Skrinar GS, et al: Physical conditioning facilitates the exercise-induced secretion of beta-endor-phin and beta-lipotropin in women. N Engl J Med 305:560-563, 1981
7. Chery-Croze S, Duclaux R: Discrimination of painful stimuli in human beings: Influence of stimulation area. J Neurophysiol 44:1-10, 1980
8. Chou J, Tang J, Costa E: MET5-Enkeph-alin-ARG6-PHE7 content of human and rabbit plasma. Life Sci 32:2589-2595, 1983
9. Czlonkowski A, Costa T, Przewlocki R, et al: Opiate receptor binding sites in human spinal cord. Brain Res 267:392-396, 1983
10. deLanerolle NC, Lamotte CC: The human spinal cord: Substance P and methionine-enkephalin immunoreactivity. J Neurosci 2:1369-1386, 1982
11. Fessler RG, Brown FD, Rachlin JR, et al: Elevated Beta-endorphin in cerebrospinal fluid after electrical brain stimulation: Artifact of contrast infusion? Science 224:1017-1018, 1984
12. Foley KM, Kourides IA, Inturrisi CE, et al: Beta-endorphin: Analgesic and hormonal effects in humans. Proc Natl Acad Sci USA 76:5377-5381, 1979
13. Furui T, Kageyama N, Kuwayama A, et al: Increase of beta-endorphin in cerebrospinal fluid after removal of ACTH-se-creting pituitary adenomas. Pain 11:127-132, 1981
14. Furui T, Kageyama N, Haga T, et al: Radioreceptor assay of methionine-en-kephalin-like substance in human cerebrospinal fluid. Pain 9:63-72, 1980
15. Gerner RH, Sharp B: CSF beta-endor-phin-immunoreactivity in normal, schizophrenic, depressed, manic and anorexic subjects. Brain Res 237:244-247, 1982
16. Gintzler AR: Endorphin-mediated increases in pain threshold during pregnancy. Science 210:193-195, 1980
17. Gramsch C, Hollt V, Mehraein P, et al: Regional distribution of methionine-enkephalin- and beta-endorphin-like immunoreactivity in human brain and pituitary. Brain Res 171:261-270, 1979
18. Grevert P, Albert LH, Goldstein A: Partial antagonism of placebo analgesia by naloxone. Pain 16:129-143, 1983
19. Hollt V, Muller OA, Fahlbusch R: Beta-endorphin in human plasma: Basal and pathologically elevated levels. Life Sci 25:27-44, 1979
20. Hosobuchi Y, Lamb S, Baskin D: Tryptophan loading may reverse tolerance to opiate analgesics in humans: A preliminary report. Pain 9:161-169, 1980
21. Houck JC, Kimball C, Chang C, et al: Placental beta-endorphin-like peptides. Science 207:78-80, 1980
22. Kaiya H, Tanaka T, Takeuchi K, et al: Decreased level of beta endorphin-like immunoreactivity in cerebrospinal fluid of patients with senile dementia of Alzheimer type. Life Sci 33:1039-1043, 1983
23. LaMotte CC, deLanerolle NC: Human spinal neurons: Innervation by both substance P and enkephalin. Neuroscience 6:713-723, 1981
24. Levine JD, Gordon NC, Smith R, et al: Analgesic responses to morphine and placebo in individuals with postoperative pain. Pain 10:379-389, 1981
25. Lewis JW, Tordoff MG, Sherman JE, et al: Adrenal medullary enkephalin-like peptides may mediate opioid stress analgesia. Science 217:557-559, 1982
26. McCain HW, Lamster IB, Bozzone JM, et al: B-Endorphin modulates human immune activity via non-opiate receptor mechanisms. Life Sci 31:1619-1624, 1982
27. Naber D, Pickar D, Dionne RA, et al: Assay of endogenous opiate receptor ligands in human CSF and plasma. Subst Alcohol Actions Misuse 1:83-91, 1980
28. Nicoll RA, Alger BE, Jahr CE: Peptides as putative excitatory neurotransmitters: Carnosine, enkephalin, substance P and TRH. Proc R Soc Lond [Biol] 210:1333-1340, 1980
29. Nyberg F, Wahlstrom A, Sjolund B, et al: Characterization of electrophoretically separable endorphins in human CSF. Brain Res 259:267-274, 1983
30. Piercey MF, Schroeder LA: Spinal and supraspinal sites for morphine and nefopam analgesia in the mouse. Eur J Pharmacol 74:135-140, 1981
31. Piercey MF, Varner K, Schroeder LA: Analgesic activity of intraspinally administered dynorphin and ethylketocyclazo-cine. Eur J Pharmacol 80:283-284, 1982
32. Pique L, Bertagna X, Javoy-Agid F, et al: Simultaneous measurement of beta-endorphin and y-lipotropin-like peptides in the human hypothalamus. Neuropeptides 2:99-108, 1981
33. Quails PJ, Sheehan PW: Electromy-ograph biofeedback as a relaxation technique: A critical appraisal and reassessment. Psychol Bull 90:21-42, 1981
34. Richardson DE: Analgesia produced by stimulation of various sites in the human beta-endorphin system. Appl Neurophysiol 45:116-122, 1982
35. Rossier J, Bloom FE, Guillemin R: Stimulation of human periaqueductal gray for pain relief increases immunoreactive beta-endorphin in ventricular fluid. Science 203:279-281, 1979
36. Sana A, Wilson SP, Molnar A, et al: Substance P and opiate-like peptides in human adrenal medulla. Neurosci Lett 20:195-200, 1980
37. Sarne Y, Azov R, Weissman BA: A stable enkephalin-like immunoreactive substance in human CSF. Brain Res 151:399-403, 1978
38. Sarne Y, Gil-Ad I, Laron Z: Regulation of hypophysial secretion by endogenous opiates: Humoral endorphin stimulates the release of growth hormone. Life Sci 28:681-686, 1981
39. Same Y, Weissman BA, Keren O, et al: Humoral endorphin: A new endogenous factor with opiate-like activity. Life Sci 28:673-680, 1981
40. Scott DS: Treatment of the myofascial pain-dysfunction syndrome: Psychological aspects. J Am Dent Assoc 101:611 -616, 1980
41. Stacher G, Bauer P, Steinringer H, et al: Effects of the synthetic enkephalin analogue FK 33-824 on pain threshold and pain tolerance in man. Pain 7:159-172, 1979
42. Steinbrook RA, Carr DB, Datta S, et al: Dissociation of plasma and cerebrospinal fluid beta-endorphin-like immunoactivity levels during pregnancy and parturition. Anesth Analg 61:893-897, 1982
330 PHYSICAL THERAPY
PRACTICE
43. Suda T, Liotta AS, Krieger DT: Beta-Endorphin is not detectable in plasma from normal human subjects. Science 202:221-223, 1978
44. Tamsen A, Sukurada T, Wahlstrom A, et al: Postoperative demand for analgesics in relation to individual levels of endorphin and substance P in cerebrospinal fluid. Pain 13:171-183, 1982
45. Taquet H, Javoy-Agid F, Hamon M, et al: Parkinson's disease affects differently met- and leu-enkephalin in the human brain. Brain Res 280:379-382, 1983
46. Volavka J, Bauman J, Pevnick J, et al: Short-term hormone effects of naloxone in man. Psychoneuroendocrinology 5: 225-234, 1980
47. Von Knorring L, Almay BGL, Johansson F, et al: Circannual variation in concentrations of endorphins in cerebrospinal fluid. Pain 12:265-272, 1982
48. Von Knorring L, Almay BGL, Johansson F, et al: Endorphins in CSF of chronic pain patients, in relation to augmenting-reducing response in visual averaged evoked response. Neuropsychobiology 5:322-326, 1979
49. Von Knorring L, Almay BGL, Johansson F, et al: Pain perception and endorphin levels in cerebrospinal fluid. Pain 5:359-365, 1978
50. Wilier JC, Albe-Fessard D: Electrophysiological evidence for a release of endogenous opiates in stress-induced analgesia in man. Brain Res 198:419-426, 1980
51. Yaksh TL, Elde RP: Release of methionine-enkephalin immunoreactivity from the rat spinal cord in vivo. Eur J Pharmacol 63:359-362, 1980
PAIN: NEUROPHARMACOLOGICAL
B. Endogenous Opiates (enkephalins)—Animal
1. Adler MW: The in vivo differentiation of opiate receptors: Introduction. Life Sci 28:1543-1545, 1981
2. Alleva E, Castellano C, Oliverio A: Effects of L- and D-amino acids on analgesia and locomotor activity of mice: Their interaction with morphine. Brain Res 198:249-252, 1980
3. Antelman SM, Rowland N: Endogenous opiates and stress-induced eating. Science 214:1149, 1981
4. Armitage SE, Baldwin BA, Vince MA: Opiate receptor function may be modulated through an oxidation-reduction mechanism. Science 208:1171-1174, 1980
5. Aronin N, DiFiglia M, Liotta AS, et al: Ultrastructural localization and biochemical features of immunoreactive leu-enkephalin in monkey dorsal horn. J Neurosci 1:561-577, 1981
6. Audigier Y, Mazarguil H, Gout R, et al: Structure-activity relationships of enkephalin analogs at opiate and enkephalin receptors: Correlation with analgesia. Eur J Pharmacol 63:35-46, 1980
7. Azami J, Llewelyn MB, Roberts MHT: Antagonism of the analgesic effects of
systemically administered morphine by injection of naloxone intracerebrally and lesions of nucleus raphe magnus. J Physiol (Lond) 306:16-17, 1979
8. Azami J, Llewelyn MB, Roberts MHT: The analgesic effects of morphine mi-croinjected into nucleus reticularis par-agigantocellularis—comparison with nucleus raphe magnus and the effects of nucleus raphe magnus lesions. J Physiol (Lond) 306:17-18, 1979
9. Barker JL, Neale JH, Smith TG Jr, et al: Opiate peptide modulation of amino acid responses suggests novel form of neuronal communication. Science 199:1451-1453, 1978
10. Barker JL, Smith TG Jr, Neale JH: Multiple membrane actions of enkephalin revealed using cultured spinal neurons. Brain Res 154:153-158, 1978
11. Barrett RW, Vaught JL: The effects of receptor selective opioid peptides on morphine-induced analgesia. Eur J Pharmacol 80:427-430, 1982
12. Beitz AJ: The sites of origin of brain stem neurotensin and serotonin projections to the rodent nucleus raphe magnus. J Neurosci 2:829-842, 1982
13. Billet M, Elghozi JL, Meyer P, et al: Central cardiovascular effects on narcotic analgesics and enkephalins in rats. Br J Pharmacol 71:365-369, 1980
14. Bloom F, Battenberg E, Rossier J, et al: Neurons containing beta-endorphin in rat brain exist separately from those containing enkephalin: Immunocyto-chemical studies. Proc Natl Acad Sci USA 75:1591-1595, 1978
15. Blum K, Briggs AH, Elston SFA, et al: Reduced leucine-enkephalin-like immunoreactive substance in hamster basal ganglia after long-term ethanol exposure. Science 216:1425-1426, 1982
16. Botticelli LJ, Wurtman RJ: Septohip-pocampal cholinergic neurons are regulated trans-synaptically by endorphin and corticotropin neuropeptides. J Neurosci 2:1316-1321, 1982
17. Carr DB, Bergland R, Hamilton A, et al: Endotoxin-stimulated opioid peptide secretion: Two secretory pools and feedback control in vivo. Science 217:845-848, 1982
18. Cesselin F, Oliveras JL, Bourgoin S, et al: Increased levels of met-enkephalin-like material in the CSF of anaesthetized cats after tooth pulp stimulation. Brain Res 237:325-338, 1982
19. Clark WG, Bemardini GL: Beta-endor-phin-induced hyperthermia in the cat. Peptides (Fayetteville) 2:371-373, 1981
20. Clark WG: Effects of opioid peptides on thermoregulation. Fed Proc 40: 2754-2759, 1981
21. Cone RI, Weber E, Barchas JD, et al: Regional distribution of dynorphin and neo-endorphin peptides in rat brain, spinal cord, and pituitary. J Neurosci 3:2146-2152, 1983
22. Craves FB, Zalc B, Leybin L, et al: Antibodies to cerebroside sulfate inhibit the effects of morphine and beta-endorphin. Science 207:75-76, 1980
23. Cuello AC: Central distribution of opioid peptides. Br Med Bull 39:11-16, 1983
24. Davies J, Dray A: Pharmacological and electrophysiological studies of morphine and enkephalin on rat supraspinal neurones and cat spinal neurones. Br J Pharmac 63:87-96, 1978
25. Egan TM, North RA: Both mu and delta opiate receptors exist on the same neuron. Science 214:923-924, 1981
26. Ferrara P, Li CH: Beta-Endorphin: Characteristics of binding sites in rabbit spinal cord. Proc Natl Acad Sci USA 77:5746-5748, 1980
27. Foutz AS, Dauthier C, Kerdelhue B: Beta-endorphin plasma levels during neuromuscular blockade in unanes-thetized cat. Brain Research 263:119-123, 1983
28. Frenk H, Urca G, Liebeskind JC: Epileptic properties of leucine- and methionine-enkephalin: Comparison with morphine and reversibility by naloxone. Brain Res 147:327-337, 1978
29. Frigeni V, Bruno F, Carenzi A, et al: Analgesia and motor activity elicited by morphine and enkephalins in two inbred strains of mice. J Pharm Pharmacol 30:310, 1978
30. Fu T-C, Dewey WL: A new technique for the in vivo bioassay of opiates and other drugs on mouse spinal cord. Eur J Pharmacol 74:239-242, 1981
31. Gambert SR, Garthwaite TL, Pontzer CH, et al: Fasting associated with decrease in hypothalamic beta-endorphin. Science 210:1271-1272, 1980
32. Gold MS, Byck R, Sweeney DR, et al: Endorphin-locus coeruleus connection mediates opiate action and withdrawal. Biomedicine 30:1-4, 1979
33. Graf L, Miglecz E, Bajusz S, et al: Met-enkephalin attentuates morphine tolerance in rats. Eur J Pharmacol 58:345-346, 1979
34. Grau JW, Hyson RL, Maier SF, et al: Long-term stress-induced analgesia and activation of the opiate system. Science 213:1409-1411, 1981
35. Havlicek V, Labella FS, Pinsky C, et al: Beta-Endorphin induces general anaesthesia by an interaction with opiate receptors. Can Anaesth Soc J 27:535-539, 1980
36. Haynes LW, Zakarian S: Morphological differentiation of enkephalin-containing neurones in tissue culture. J Physiol (Lond) 295:34-35, 1979
37. Haynes LW: Development of neuroten-sin-immunoreactive nerve cells in organotypic cultures of embryonic rat spinal cord. Neurosci Lett 19:185-190, 1980
38. Haynes LW, Smyth DG, Zakarian S: Beta endorphin immunoreactivity in developing rat spinal cord cultures. J Physiol (Lond) 301:91-92, 1979
39. Haynes LW, Zakarian S: Microanatomy of enkephalin-containing neurones in the developing rat spinal cord in vitro. Neuroscience 6:1899-1916,1981
40. Hazum E, Chang K-J, Cuatrecasas P: Opiate (enkephalin) receptors of neuroblastoma cells: Occurrence in clusters on the cell surface. Science 206:1077-1079, 1979
Volume 65 / Number 3, March 1985 331
41. Hazum E, Chang K-J, Cuatrecasas P: Specific nonopiate receptors for beta-endorphin. Science 205:1033-1035, 1979
42. Hentall ID, Fields HL: Actions of opiates, substance P, and serotonin on the excitability of primary afferent terminals and observations on interneu-ronal activity in the neonatal rat's dorsal horn in vitro. Neuroscience 9:521-528, 1983
43. Hill RG, Pepper CM: The depression of thalamic nociceptive neurones by D-ala2, and D-leu5-enkephalin. Eur J Pharmacol 47:223-225, 1978
44. Hughes J: Biogenesis, release and in-activation of enkephalins and dynaor-phins. Br Med Bull 39:17-24, 1983
45. Huidobro-Toro JP, Yoshimura K, Way EL: Application of an irreversible opiate antagonist (beta-FNA, beta-Funal-trex-amine) to demonstrate dynorphin selectivity for K-opioid sites. Life Sci 31:2409-2416,1982
46. Hunt SP, Kelly JS, Emson PC: The electron microscopic localization of methionine-enkephalin within the superficial layers (I and II) of the spinal cord. Neuroscience 5:1871-1890, 1980
47. Jacquet YF: Beta endorphin and ACTH—opiate peptides with coordinated roles in the regulation of behaviour? Trends in Neurological Sciences 140-143, 1979
48. Jacquet YF: Opiate effects after adren-ocorticotrophin or beta-endorphin injection in the periaqueductal gray matter of rats. Science 201:1032-1034, 1978
49. Jurna I: Spinal reflexes: What can they tell the pharmacologist? Trends in Pharmacological Sciences 2:241-243, 1981
50. Jurna I, Heinz G: Antinociceptive effect of morphine, opioid analgesics and haloperidol injected into the caudate nucleus of the rat. Naunyn Schmiede-bergs Arch Pharmacol 309:145-151, 1979
51. Jurna I, Heinz G: Differential effects of morphine and opioid analgesics on A and C fibre-evoked activity in ascending axons of the rat spinal cord. Brain Res 171:573-576, 1979
52. Kamerling SG, Martin WR, Wu KM, et al: Medullary K hyperalgesic mechanisms II: The effects of ethylketazocine administered into the fourth cerebral ventricle of the conscious dog. Life Sci 33:1839-1843,1983
53. Kastin AJ, Jemison MT, Coy DH: Analgesia after peripheral administration of enkephalin and endorphin analogues. Pharmacol Biochem Behav 11:713-716,1979
54. Katz RJ, Roth KA: Stress induced grooming in the rat—an endorphin mediated syndrome. Neurosci Lett 13:209-212, 1979
55. Kelly PD, Rance MJ, Traynor JR: Properties of opiate binding in the rat spinal cord. Neuropeptides 2:319-324, 1982
56. Kerdelhue B, Bethea CL, Ling N, et al: Beta-Endorphin concentrations in serum hypothalamus and central gray of hypophysectomized and mediobasal
hypothalamus lesioned rats. Brain Res 231:85-91,1982
57. Kleckner RC: Leucine enkephalin: Localization in and axoplasmic transport by sacral parasympathetic preganglionic neurons. Science 208:1479-1482,1980
58. Kolata G: Brain receptors for appetite discovered. Science 218:460-461, 1982
59. Krieger DT: Brain peptides: What, where, and why? Science 222:975-985, 1983
60. Kunos G, Farsang C, Ramirez-Gon-zales MD: Beta-Endorphin: Possible involvement in the antihypertensive effect of central alpha-receptor activation. Science 211:82-84, 1981
61. Larson AA, Vaught JL, Takemori AE: The potentiation of spinal analgesia by leucine enkephalin. Eur J Pharmacol 61:381-383,1980
62. Larsson L-I, Childers S, Snyder SH: Met- and Leu-enkephalin immunoreac-tivity in separate neurones. Nature 282:407-410, 1979
63. Lewis ME, Mishkin M, Bragin E, et al: Opiate receptor gradients in monkey cerebral cortex: Correspondence with sensory processing hierarchies. Science 211:1166-1169, 1981
64. Lewis RV, Stern AS, Kimura S, et al: All about 50,000-dalton protein in adrenal medulla: A common precursor of met- and leu-enkephalin. Science 208:1459-1461, 1980
65. Liotta AS, Yamaguchi H, Krieger DT: Biosynthesis and release of beta-endorphin-, N-acetyl beta-endorphin-, beta-endorphin-(1-27)-, and N-acetyl beta-endorphin-(1-27)-like peptides by rat pituitary neurointermediate lobe: Beta-endorphin is not further processed by anterior lobe. J Neurosci 1:565-595, 1981
66. Liston DR, Vanderhaeghen JJ, Rossier J: Presence in brain of synenkephalin: A proenkephalin-immunoreactive protein which does not contain enkephalin. Nature 302:62-65, 1983
67. Mack KJ, Killian A, Weyhenmeyer JA: Comparison of Mu, Delta, and Kappa opiate binding sites in rat brain and spinal cord. Life Sci 34:281-285, 1984
68. Mauk MD, Madden J, Barchas JD, et al: Opiates and classical conditioning: Selective abolition of conditioned responses by activation of opiate receptors within the central nervous system. Proc Natl Acad Sci USA 79:7598-7602, 1982
69. Martin GE, Bacino CB: Action of inter-cerebrally injected beta-endorphin on the rat's core temperature. Eur J Pharmacol 59:227-236, 1979
70. Martin MM, Martin JS: Specific-opiate-induced depression of transmitter release from dorsal root ganglion cells in culture. Science 199:1449-1455, 1978
71. Mathur KB, Dhotre BJ, Raghubir R, et al: Morphine like activity of some new met-enkephalin analogues. Life Sci 25:2023-2028, 1979
72. Matsukura S, Yoshimi H, Sueoka S, et al: The regional distribution of immu-
noreactive beta-endorphin in the monkey brain. Brain Res 159:228-233, 1978
73. Meites J, Bruni JF, VanVugt DA, et al: Relation of endogenous opioid peptides and morphine to neuroendocrine functions. Life Sci 24:1325-1336, 1979
74. Meyerson BJ: Neonatal beta-endorphin and sexual behavior. Acta Physiol Scand 115:159-160,1982
75. Mickley GA, Stevens KE, White GA, et al: Endogenous opiates mediate radiogenic behavioral change. Science 220:1185-1187, 1983
76. Mollenhauer HH, Morre DJ: Attenuation of amnesia in rats by systemically administered enkephalins. Science 200:83-86, 1978
77. Morley JE, Kelson MK, Levine AS, et al: The effects of stress on central nervous sytem concentrations of the opioid peptide, dynorphin. Peptides (Fayette-ville) 3:901-906, 1982
78. Morley JE, Levine AS: Stress-induced eating is mediated through endogenous opiates. Science 209:1259-1260, 1980
79. Moss MS, Glazer EJ, Basbaum Al: En-kephalin-immunoreactive perikarya in the cat raphe dorsalis. Neurosci Lett 21:33-37, 1981
80. Moss MS, Glazer EJ, Basbaum Al: The peptidergic organization of the cat periaqueductal gray: I. The distribution of immunoreactive enkephalin-containing neurons and terminals. J Neurosci 3:603-616, 1983
81. Oh TH, Markelonis GJ: Different brain areas mediate the analgesic and epileptic properties of enkephalin. Science 200:225-338, 1978
82. Oka T, Negishi K, Kajiwara M, et al: The choice of opiate receptor subtype by neo-endorphins. Eur J Pharmacol 79:301-305, 1982
83. Pacheco P, Ervin FR, Hodgdon JC: Effects of leucine5- and methionine5- Betah- endorphin on behavior and electroencephalogram in cats. Life Sci 32:181-190, 1983
84. Pasternak GW: Opiate, enkephalin, and endorphin analgesia: Relations to a single subpopulation of opiate receptors. Neurology 31:1311-1315, 1981
85. Pasternak GW, Gintzler AR, Houghten RA, et al: Biochemical and Pharmacol evidence for opioid receptor multiplicity in the central nervous system. Life Sci 33:167-173, 1983
86. Patey G, De La Baume S, Schwartz J-C: Selective protection of methionine enkephalin released from brain slices by enkephalinase inhibition. Science 212:1153-1155, 1981
87. Pollard H, Llorens C, Schwartz JC, et al: Localization of opiate receptors and enkephalins in the rat striatum in relationship with the nigrostriatal dopaminergic system: Lesion studies. Brain Res 151:392-398, 1978
88. Pomeranz B, Gurevich N: Effects of enkephalin analogue and naloxone on cat spinal cord dorsal root potentials. Eur J Pharmacol 60:307-313,1979
332 PHYSICAL THERAPY
PRACTICE
89. Przewlocki R, Hollt V, Duka TH, et al: Long-term morphine treatment decreases endorphin levels in rat brain and pituitary. Brain Res 174:357-361, 1979
90. Przewlocki R, Lason W, Konecka AM, et al: The opioid peptide dynorphin, circadian rhythms, and starvation. Science 219:71-73, 1983
91. Quirion R, Pert CB: Dynorphins: Similar relative potencies on mu, 8- and k-opiate receptors. Eur J Pharmacol 76:467-468, 1981
92. Reith MEA, Sershen H, Vadasz C, et al: Strain differences in opiate receptors in mouse brain. Eur J Pharmacol 74:377-380, 1981
93. Rosenfeld JP, Keresztes-Nagy P: Differential effects of intracerebrally mi-croinjected enkephalin analogs on centrally versus peripherally induced pain, and evidence for a facial versus lower body analgesic effect. Pain 9:171 -181, 1980
94. Rossier J, Guillemin R, Bloom F: Foot shock induced stress decreases leu5-enkephalin immunoreactivity in rat hypothalamus. Eur J Pharmacol 48:465-466, 1978
95. Ruda MA: Opiates and pain pathways: Demonstration of enkephalin synapses on dorsal horn projection neurons. Science 215:1523-1525, 1982
96. Satoh M, Kawajiri SI, Ukai Y, et al: Selective and non-selective inhibition by enkephalins and noradrenaline of nociceptive response of lamina V type neurons in the spinal dorsal horn of the rabbit. Brain Res 177:384-387, 1979
97. Schlen H, Bentley GA: The possibility that a component of morphine-induced analgesia is contributed indirectly via the release of endogenous opioids. Pain 9:73-84, 1980
98. Shani J, Azov R, Weissman BA: Enkephalin levels in rat brain after various regimens of morphine administration. Neurosci Lett 12:319-322, 1979
99. Shyu B-C, Andersson SA, Thoren P: Endorphin mediated increase in pain threshold induced by long-lasting exercise in rats. Life Sci 30:833-840, 1982
100. Shavit Y, Lewis JW, Terman GW: Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity. Science 223:188-190, 1984
101. Simantov R: Glucocorticoids inhibit endorphin synthesis by pituitary cells. Nature 280:684-685, 1979
102. Smith BR, Brown ZW, Amit Z: Intraventricular self-administration of leucine-enkephalin by laboratory rats. Life Sci 31:1527-1530, 1982
103. Stevens CW, Pezalla PD: A spinal site mediates opiate analgesia in frogs. Life Sci 33:2097-2103,1983
104. Sykova E, Kriz N, Hajek I: Possible analgetic effect of endogenous and synthetic opiate-like peptides at the spinal level. Relation to poststimulation analgesia. Activitas Nervosa Superior (Prague) 24:199-200,1982
105. Takagi H, Shiomi H, Kuraishi Y, et al: Pain and the bulbospinal noradrenergic
system: Pain-induced increase in nor-metanephrine content in the spinal cord and its modification by morphine. Eur J Pharmacol 54:99-107, 1979
106. Tung AS, Yaksh TL: The antinociceptive effects of epidural opiates in the cat: Studies on the pharmacology and the effects of lipophilicity in spinal analgesia. Pain 12:343-356, 1982
107. Urca G, Frenk H: Systemic morphine blocks the seizures induced by intra-cerebroventricular (i.c.v.) injections of opiates and opioid peptides. Brain Res 246:121-126, 1982
108. Wamsley JK, Zarbin MA, Young WS III, et al: Distribution of opiate receptors in the monkey brain: An autoradiographic study. Neurosci 7:595-613, 1982
109. Waterfield AA, Leslie FM, Lord JAH, et al: Opioid activities of fragments of beta-endorphin and of its leucine65-an-alogue. Comparison of the binding properties of methionine- and leucine-enkephalin. Eur J Pharmacol 48:11 -18, 1979
110. Wolozin BL, Pasternak GW: Classification of multiple morphine and enkephalin binding sites in the central nervous system. Proc Natl Acad Sci USA 78:6181-6185, 1981
111. Wu KM, Martin WR, Kamerling SG, et al: Possible medullary k hyperalgesic mechanism: I. A new potential role for endogenous opioid peptides in pain perception. Life Sci 33:1831-1838, 1983
112. Yaksh TL: Spinal opiate analgesia: Characteristics and principles of action. Pain 11:293-346,1981
113. Yaksh TL, Elde RP: Factors governing release of methionine enkephalin-like immunoreactivity from mesencephalon and spinal cord of the cat in vivo. J Neurophysiol 48:1056-1075, 1981
114. Yaksh TL, Gross KE, Li CH: Studies in the intrathecal effect of beta-endorphin in primates. Brain Res 241:261-269, 1982
115. Yang H-YT, Fratta W, Hong JS, et al: Detection of two endorphin-like peptides in nucleus caudalus. Neuropharmacology 17:443-448, 1978
116. Yashpal K, Henry JL: Endorphins mediate overshoot of substance P-in-duced facilitation of a spinal nociceptive reflex. Can J Physiol Pharmacol 61:303-307, 1983
117. Yeung JC, Yaksh TL, Rudy TA: Concurrent mapping of brain sites for sensitivity to the direct application of morphine and focal electrical stimulation in the production of antinociception in the rat. Pain 4:23-40, 1977
118. Young WS, Wamsley JK, Zarbin MA, et al: Opioid receptors undergo axonal flow. Science 210:76-78, 1980
PAIN: NEUROPHARMACOLOGICAL
C. Serotonergic Mechanisms 1. Aiello-Malmberg P, Bartolini A, Bartolina
R, et al: Effects of morphine, physostig-mine and raphe nuclei stimulation on 5-
hydroxytryptamine release from the cerebral cortex of the cat. Br J Pharmacol 65:547-555, 1979
2. Andersen E, Dafny N: Microiontophor-etically applied 5-HT reduces responses to noxious stimulation in the thalamus. Brain Res 241:176-178, 1982
3. Berge O-G: Effects of 5-HT receptor agonists and antagonists on a reflex response to radiant heat in normal and spinally transected rats. Pain 13:253-266, 1982
4. Berge O-G, Hole K, Dahle H: Nociception is enhanced after low doses and reduced after high doses of the serotonin receptor agonist 5-methoxy-N, N-dimethyl-tryptamine. Neurosci Lett 19:219-223, 1980
5. Chitour D, Dickenson AH, LeBars D: Pharmacological evidence for the involvement of serotonergic mechanisms in diffuse noxious inhibitory controls (DNIC). Brain Res 236:329-337, 1982
6. Deakin JFW, Dostrovsky JO: Involvement of the periaqueductal grey matter and spinal 5-Hydroxytryptaminergic pathways in morphine analgesia: Effects of lesions and 5 Hydroxytryptamine depletion. Br J Pharmac 63:159-165, 1978
7. Guilbaud G, Peschanski M, Gautron M, et al: Responses of neurons of the nucleus raphe magnus to noxious stimuli. Neurosci Lett 17:149-154, 1980
8. Jeftinija S, Kemba K, Ranic M: Norepinephrine reduces excitability of single cutaneous primary afferent C-fibers in the cat spinal cord. Brain Res 219:456-463, 1981
9. Messing RB, Lytle LD: Serotonin-containing neurons: Their possible role in pain and analgesia. Pain 4:1-21, 1978
10. Nahmod VE, Finkielman S, Benarroch EE, et al: Angiotensin regulates release and synthesis of serotonin in brain. Science 202:1091-1093,1978
11. Oliveras JL, Bourgoin S, Henry F, et al: The topographical distribution of sero-toninergic terminals in the spinal cord of the cat: Biochemical mapping by the combined use of microdissection and mi-croassay procedures. Brain Res 138:393-406, 1979
12. Oliveras JL, Guilbaud G, Besson JM: A map of serotoninergic structures involved in stimulation producing analgesia in unrestrained freely moving cats. Brain Res 164:317-322, 1979
13. Proudfit HK, Larson AA, Anderson EG: The role of GABA and serotonin in the mediation of raphe-evoked spinal cord dorsal root potentials. Brain Res 195:149-165, 1980
14. Rivot JP, Chaouch A, Besson JM: Nucleus raphe magnus modulation of response of rat dorsal horn neurons to unmyelinated fiber inputs: Partial involvement of serotonergic pathways. J Neurophysiol 44:1039-1057, 1980
15. Ruda MA, Coffield J, Steinbusch HWM: Immunocytochemical analysis of serotonergic axons in laminae I and II of the lumbar spinal cord of the cat. J Neurosci 2:1660-1671, 1982
16. Soja PJ, Sinclair JG: Evidence that noradrenaline reduces tonic descending in-
Volume 65 / Number 3, March 1985 333
hibitlon of cat spinal cord nociceptor-driven neurones. Pain 15:71-81,1983
17. Weil-Fugazza J, Godefroy F, Besson JM: Changes in brain and spinal tryptophan and 5-hydroxy-idoleacetic acid levels following acute morphine administration in normal and arthritic rats. Brain Res 175:291-301, 1979
18. Wessendorf MW, Proudfit HK, Anderson EG: The identification of serotonergic neurons in the nucleus raphe magnus by conduction velocity. Brain Res 214:168-173, 1981
19. Wilier JC, Roby A, Gerard A, et al: Electrophysiological evidence for a possible serotonergic involvement in some endogenous opiate activity in humans. Eur J Pharmacol 78:117-120,1982
20. Yaksh TL: Direct evidence that spinal serotonin and noradrenaline terminals mediate the spinal antinociceptive effects of morphine in the periaqueductal gray. Brain Res 160:180-185, 1979
21. Yaksh TL, Tyce GM: Microinjection of morphine into the periaqueductal gray evokes the release of serotonin from spinal cord. Brain Res 171:176-181, 1979
22. Zemlan FP, Corrigan SA, Pfaff DW: Noradrenergic and serotonergic mediation of spinal analgesia mechanism. Eur J Pharmacol 61:111-124,1980
PAIN: NEUROPHARMACOLOGICAL
D. Opiate Antagonists 1. Arnsten AFT, Segal DS, Neville HJ, et al:
Naloxone augments electrophysiological signs of selective attention in man. Nature 304:725-727, 1983
2. Boureau F, Wilier JC, Dauthier C: Study of naloxone in normal awake man: Effects on spinal reflexes. Journal of Neuropharmacology 17:565-568, 1978
3. Bridges RS, Grimm CT: Reversal of morphine disruption of maternal behavior by concurrent treatment with the opiate antagonist naloxone. Science 218:166-168,1982
4. Brown DR, Holtzman SG: Narcotic antagonists attenuate drinking induced by water deprivation in a primate. Life Sci 28:1287-1294, 1981
5. Brown DR, Holtzman SG: Suppression of drinking by naloxone in the rat: A further characterization. Eur J Pharmacology 69:331-340,1981
6. Calvillo O, Henry JL, Neuman RS: Actions of narcotic analgesics and antagonists on spinal units responding to natural stimulation in the cat. Can J Physiol Pharmacol 57:652-663, 1979
7. Coderre TJ, Rollman GB: Naloxone hyperalgesia and stress-induced analgesia in rats. Life Sci 32:2139-2146, 1983
8. Doi T, Jurna I: Intrathecal substance P depresses the tail-flick response-antagonism by naloxone. Naunyn Schmiede-bergs Arch Pharmacol 317:135-139, 1981
9. Dum J, Blasig J, Meyer G, Herz A: Opiate antagonist-receptor interaction unchanged by acute or chronic opiate treat
ment. Eur J Pharmacol 55:375-383, 1979
10. Faden Al, Holaday JW: Opiate antagonists: A role in the treatment of hypovolemic shock. Science 205:317-318, 1979
11. Faden Al, Jacobs TP, Mougey E, Holaday JW: Endorphins in experimental spinal injury: Therapeutic effect of naloxone. Ann Neurol 10:326-332, 1981
12. Fitzgerald M, Woolf CJ: The stereospe-cific effect of naloxone on rat dorsal horn neurones: Inhibition in superficial laminae and excitation in deeper laminae. Pain 9:293-306,1980
13. French ED, Vasquez SA, George R: Behavioral changes produced in the cat by acute and chronic morphine injection and naloxone precipitated withdrawal. Eur J Pharmacol 57:387-397, 1979
14. Gallagher M, King RA, Young NB: Opiate antagonists improve spatial memory. Science 221:975-976, 1983
15. Gessa GL, Paglietti E, Quarantotti BP: Induction of copulatory behavior in sexually inactive rats by naloxone. Science 204:203-304, 1979
16. Goldfoot DA, Essock-Vitale SM, Asa CS, et al: Endorphine: Naloxone fails to alter experimental pain or mood in humans. Science 199:1093-1096, 1978
17. Grevert P, Baizman ER, Goldstein A: Naloxone effects on a nociceptive response of hypophysectomized and ad-renalectomized mice. Life Sci 23:723-728, 1978
18. Gruol DL, Smith TG: Opiate antagonism of glycine-evoked membrane polarizations in cultured mouse spinal cord neurons. Brain Res 223:355-365, 1981
19. Henry JL: Naloxone excites nociceptive units in the lumbar dorsal horn of the spinal cat. Neuroscience 4:1485-1491, 1979
20. Henry JL: Diurnal variation in excitation of dorsal horn units by naloxone in the spinal cat suggests a circulating opioid factor. Neuroscience 6:1935-1942, 1981
21. Hill RG: The status of naloxone in the identification of pain control mechanisms operated by endogenous opioids. Neu-rosci Lett 21:217-222, 1981
22. Hill RG, Morris R, Sofroniew MV: Naloxone reversible inhibition of reticular neurones in the rat caudal medulla produced by electrical stimulation of the periaqueductal grey matter. Pain 15:249-263,1983
23. Hiller JM, Angel LM, Simon EJ: Multiple opiate receptors: Alcohol selectively inhibits binding to delta receptors. Science 214:468-469, 1981
24. Iversen LL, Iversen SD, Bloom FE, et al: Release of enkephalin from rat globus pallidus in vitro. Nature 271:679-681, 1978
25. Kurrlazawa T, Tadaki E, Kim K: Naloxone effects on the blood pressure response induced by thin-fiber muscular afferents. Brain Res 205:452-456, 1981
26. Kuraishi Y, Satoh M, Harada Y, et al: Analgesic action of intrathecal and intracerebral beta-endorphin in rats: Comparison with morphine. Eur J Pharmacol 67:143-146,1980
27. Larson AA: Nociception in mice after chronic stress and chronic narcotic antagonists during maturation. Brain Res 243:323-328, 1982
28. LeBars D, Chitour D, Kraus E, et al: Effect of naloxone upon diffuse noxious inhibitory controls (DNIC) in the rat. Brain Res 204:387-402, 1981
29. Martin WR: History and development of mixed opioid and development of mixed opioid agonists, partial agonists and antagonists. Br J Clin Pharmacol 7:273-279, 1979
30. McGivern RF, Berntson GG: Mediation of diurnal fluctuations in pain sensitivity in the rat by food intake patterns: Reversal by naloxone. Science 210:210-211, 1980
31. Pasternak GW, Childers SR, Snyder SH: Naloxazone, a long-acting opiate antagonist: Effects on analgesia in intact animals and on opiate receptor binding in vitro. J Pharmacol Exp Ther 214:455-462, 1980
32. Pasternak GW, Childers SR, Snyder SH: Opiate analgesia: Evidence for mediation by a subpopulation of opiate receptors. Science 208:514-516, 1980
33. Pilcher CWT: Repeated administration of naltrexone produces tolerance to nalox-one-induced hyperalgesia. Life Sci 27: 1905-1909, 1980
34. Ramabadran K, Sim MK, Lun KC: Neuromuscular effects of some opioid agonists and anatagonists. Jpn J Pharmacol 33:73-78, 1983
35. Saaverdra JM: Naloxone reversible decrease in pain sensitivity in young and adult spontaneously hypertensive rats. Brain Res 209:245-249, 1981
36. Sawynok J, Labella FS: Naloxone antagonizes inhibitory and unmasks excitatory effects of baclofen. J Pharm Pharmacol 33:597-599, 1981
37. Sawynok J, Pinsky C, LaBella FS: Mini review on the specificity of naloxone as an opiate antagonist. Life Sci 25:1621-1632,1979
38. Stevens DR, Klemm WR: Morphine-nal-oxone interactions: A role for nonspecific morphine excitatory effects in withdrawal. Science 250:1379-1380, 1979
39. Tang AH, Collins RJ: Enhanced analgesic effects of morphine after chronic administration of naloxone in the rat. Eur J Pharmacol 47:473-474, 1978
40. Tang AH, Schoenfeld MJ: Comparison of subcutaneous and spinal subarachnoid injections of morphine and naloxone on analgesic tests in the rat. Eur J Phar-mac 52:215-223, 1978
41. Tulunay FC, Yano I, Takemori AE: Enhanced naloxone potency and the development of narcotic tolerance. Eur J Pharmacol 53:247-253, 1979
42. Watson SJ, Berger PA, Akil H, et al: Effects of naloxone on schizophrenia: Reduction in hallucinations in a subpopulation of subjects. Science 201:73-76, 1978
43. White JM, Holtzman SG: The effects of naloxone, diprenorphine, and diazepam on responding suppressed by pre-shock and pre-food stimuli. Life Sci 32:479-486, 1982
334 PHYSICAL THERAPY
PRACTICE
44. Wilson PR, Yaksh TL: Baclofen is antinociceptive in the spinal intrathecal space of animals. Eur J Pharmacol 51:323-330, 1978
45. Yaksh TL, Howe JR: Opiate receptors and their definition by antagonists. Anesthesiology 56:246-249, 1982
46. Yeung JC, Rudy TA: Multiplicative interaction between narcotic agonisms expressed at spinal and supraspinal sites of antinociceptive action as revealed by concurrent intrathecal and intracerebro-ventricular injections of morphine. J Pharmacol Exp Ther 215:633-642, 1980
47. Yeung JC, Rudy TA: Sites of antinociceptive action of systemically injected morphine: Involvement of supraspinal loci as revealed by intracerebroventricu-lar injection of naloxone. J Pharmacol Exp Ther 215:626-632, 1980
48. Young AM, Woods JH: Limitations on the antagonistic actions of opioid antagonists. Federation Proc 41:2333-2338, 1982
PAIN: NEUROPHARMACOLOGICAL
E. Neurotransmitters, Morphine, and Other Drugs
1. Amir S: Effects of ACTH on pain responsiveness in mice: Interaction with morphine. Neuropharmacology 20:959-962, 1981
2. Auguy-Valette A, Cros J, Gouarderes C, et al: Morphine analgesia and cerebral opiate receptors: A developmental study. Br J Pharmacol 63:303-308, 1978
3. Baraban JM, Wang RY, Aghajanian GK: Reserpine suppression of dorsal raphe neuronal firing: Mediation by adrenergic system. Eur J Pharmacol 52:27-36, 1978
4. Berge O-G, Hole K: Tolerance to the antinociceptive effect of morphine in the spinal rat. Neuropharmacology 20:653-657,1981
5. Chan SHH: Participation of the nucleus reticularis gigantocellularis in the morphine suppression of jaw-opening reflex in cats. Brain Res 160:277-280, 1979
6. Clark WG, Bemardini GL: Morphine-induced hyperthermia: Lack of cross-tolerance with enkephalin analogs. Brain Res 231:231-234, 1982
7. Cohn ML, Cohn M, Taylor FH: Guano-sine 3', 5'-monophosphate: A central nervous system regulator of analgesia. Science 199:319-322, 1978
8. Collins JG, Bock J, Homma E, et al: Serum morphine levels in cats during dorsal horn neuron suppression by spin-ally administered morphine. Life Sci 31:2145-2148, 1982
9. Dafny N, Burks TF: Selective modification by opiates of neuronal activity of the medial basal hypothalamus. Exp Neurol 72:1-11,1981
10. Davies J, Dray A: Depression and facilitation of synaptic responses in cat dorsal horn by substance P administered into substantia gelatinosa. Life Sci 27:2037-2042, 1980
11. Delander GE, Takemori AE: Spinal antagonism of tolerance and dependence induced by systemically administered morphine. Eur J Pharmacol 94:35-42, 1983
12. Doi T, Jurna I: Intrathecal substance P depresses spinal motor and sensory responses to spina® stimulation of nociceptive afferents—antagonism by naloxone. Naunyn Schmiedebergs Arch Pharmacol 319:154-160, 1982
13. Einsppahr FJ, Piercey MF: Morphine depresses dorsal horn neuron responses to controlled noxious and non-noxious cutaneous stimulation. J Pharmacol Exp Ther 213:456-461, 1980
14. Frederickson RCA, Burgiss V, Harrell CE, et al: Dual actions of substance P on nociception: Possible role of endogenous opioids. Science 199:1359-1362, 1978
15. Frenk H, Liban A, Balamuth R, et al: Opiate and non-opiate aspects of morphine induced seizures. Brain Res 253:253-261, 1982
16. Gebhert GF, Sandkuhler J, Thalhammer JG, et al: Inhibition in spinal cord of nociceptive information by electrical stimulation and morphine microinjection at identical sites in midbrain of the cat. J Neurophysiol 51:75-89, 1984
17. Haigler HJ, Spring DD: Substance P, morphine and methionine-enkephalin: Effects on spontaneous and evoked neuronal firing in the nucleus reticularis gigantocellularis of the rat. Eur J Pharmacol 67:65-74, 1980
18. Hammond DL, Levy RA, Proudfit HK: Hypoalgesia following microinjection of noradrenergic antagonists in the nucleus raphe magnus. Pain 9:85-101, 1980
19. Henderson G, Hughes J, Kosterlitz HW: In vitro release of leu- and met-enkeph-alin from the corpus striatum. Nature 271:677-679, 1982
20. Hosford DA, Haigler HJ: Morphine and methionine-enkephalin: Different effects on spontaneous and evoked neuronal firing in the mesencephalic reticular formation of the rat. J Pharmacol Exp Ther 213:355-363, 1980
21. Iversen LL, Iversen SD, Bloom FE, et al: Release of enkephalin from rat globus pallidus in vitro. Nature 271:679-681, 1978
22. Joyce EM, Iversen SD: The effect of morphine applied locally to mesencephalic dopamine cell bodies on spontaneous motor activity in the rat. Neurosci Lett 14:207-212, 1979
23. Jurna I: Aminophyline differentiates between the depressant effects of morphine on the spinal nociceptive reflex and on the spinal ascending activity evoked from afferent C fibres. Eur J Pharmacol 71:393-400,1981
24. Jurna I, Heinz G, Blinn G, et al: The effect of substantia nigra stimulation and morphine on A-motoneurones and the tail-flick response. Eur J Pharmacol 51:239-250,1978
25. Jurna I, Zetler G: Antinociceptive effect of centrally administered caerulein and cholecystokinin octapeptide (CCK-8). Eur J Pharmacol 73:323-331, 1981
26. Klemm WR, Mallari CG: Effects of morphine and naloxone on the responsiveness (unit and field potential) of three opiate-relevant brain areas during electrical stimulation of the substantia nigra. Prog Neuropsychopharmacol Biol Psychiatry 4:1-12, 1980
27. Konishi S, Tsunoo A, Otsuka M: Enkephalins presynaptically inhibit cholinergic transmission in sympathetic ganglia. Nature 383:515-516,1979
28. Konishi S, Tsunoo A, Otsuka M: Substance P and noncholinergic excitatory synaptic transmission in guinea pig sympathetic ganglia. Proceedings of the Japan Academy 55:525-530, 1979
29. Kostowski W, Jerlicz M, Bidzinski A, et al: Reduced analgesic effects of morphine after bilateral lesions of the locus coeruleus in rats. Pol J Pharmacol Pharm 39:49-53,1978
30. Kuriyama K, Yoneda Y: Morphine induced alterations of y-aminobutyric acid and taurine contents and L-glutamate decarboxylase activity in rat spinal cord and thalamus: Possible correlates with analgesic action of morphine. Brain Res 148:163-179, 1978
31. Levy RA, Proudfit HK: Analgesia produced by microinjection of baclofen and morphine at brain stem sites. Eur J Pharmacol 57:43-55, 1979
32. Lewis JW, Sherman JE, Liebeskind JC: Opioid and non-opioid stress analgesia: Assessment of tolerance and cross-tolerance with morphine. J Neurosci 1:358-363,1981
33. Lineberry CG, Kulics AT: The effects of diazepam, morphine and lidocaine on nociception in rhesus monkeys: A signal detection analysis. J Pharmacol Exp Ther 205:302-310, 1978
34. Lorez HP, Kemali M: Substance P-, met-enkephalin-and somatostatin-like immu-noreactivity distribution in the frog spinal cord. Neurosci Lett 26:119-124, 1981
35. Murase K, Nedeljkov V, Randic M: The actions of neuropeptides on dorsal horn neurons in the rat spinal cord slice preparation: An intracellular study. Brain Res 234:170-176, 1982
36. Palmer MR, Klemm WR: Adrenergic alteration of morphine-induced suppression of sciatic-evoked unit responses in the central grey. Progress in Neuro-Psy-chopharmacology 2:337-347, 1978
37. Piercey MF, Dorbry PJK, Schroeder LA, et al: Behavioral evidence that substance P may be a spinal cord sensory neurotransmitter. Brain Res 210:407-412, 1981
38. Pomeroy SL, Behbehani MM: Response of nucleus raphe magnus neurons to iontophoretically applied substance P in rats. Brain Res 202:464-468, 1980
39. Proudfit HK, Levy RA: Delimitation of neuronal substrates necessary for the analgesic action of baclofen and morphine. Eur J Pharmacol 47:159-166, 1978
40. Randic M, Carstens E, Zimmermann M, et al: Dual effects of substance P on the excitability of single cutaneous primary afferent C- and A-fibers in the cat spinal cord. Brain Res 233:389-393,1982
Volume 65 / Number 3, March 1985 335
41. Schwartz AS, Woolf B, Hedin C, et al: Dissociation of discrimination of skin warming from skin cooling by morphine in monkeys. Brain Res 156:206-210, 1978
42. Slater P, Blundell C: The effects of a permanent and selective depletion of brain catecholamines on the antinociceptive action of morphine. Arch Pharm (Weinheim) 305:337-343, 1978
43. Snyder SH: Brain peptides as neurotransmitters. Science 209:976-983, 1980
44. Soja PJ, Sinclair JG: Spinal vs supraspinal actions of morphine on cat spinal cord multireceptive neurons. Brain Res 273:1-7, 1983
45. Tessler A, Himes BT, Artymyshyn R, et al: Spinal neurons mediate return of substance P following deafferentation of cat spinal cord. Brain Res 230:263-281, 1981
46. Urca G, Nahin RL, Liebeskind JC: Development of tolerance to the effects of morphine: Association between analgesia and electrical activity in the periaqueductal gray matter. Brain Res 176:202-207, 1979
47. Wood PL: Multiple opiate receptors: Support for unique mu, delta and kappa sites. Neuropharmacol 21:487-497, 1982
48. Yaksh TL, Wilson PR, Kaiko RF, et al: Analgesia produced by a spinal action of morphine and effects upon parturition in the rat. Anesthesiology 51:386-392, 1979
49. Yasphal K, Wright DM, Henry JL: Substance P reduces tail-flick latency: Implications for chronic pain syndrome. Pain 14:155-167, 1982
336 PHYSICAL THERAPY