Neurology II 2.07 Pain Dr. Camara Chua[1]

Subject:Topic:Lecturer:Date:

Neurology II2.07 – Neurology of PainDra. Pia Camara-ChuaAugust 24, 2015

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OUTLINEI. PainII. Anatomy and Physiology of PainIII. Spinal Afferent Tracts for PainIV. Other Spinocerebral Afferent TractsV. Thalamic Terminus of Pain FibersVI. Physiologic Aspects of PainVII. Clinical and Physiologic Aspects of PainVIII. Approach to the Patient with Pain as the Predominant Symptom

IX. Treatment of Intractable PainX. Supplemental Medication for the Treatment of PainXI. Treatment of Neuropathic PainXII. Treatment of Reflex Sympathetic DystrophyXIII. Ablative Surgery in the Treatment of PainXIV. Non-Medical Methods for the Treatment of PainXV. Appendix

OBJECTIVESAt the end of the lecture, the student should be able to:

1. No objectives were given.2. But to study this Trans, we know it will be a bit dull and dry. But

just know the key points in each heading as well as remember important structures and pathways involved in neurology of pain.

3. It will be helpful if you know by heart the pathways of pain. 4. Also know treatment modalities for pain.

References: 2015B Trans, Dra’s .ppt, Adam’s Neurology

I. PAIN Pain stands pre-eminent among all the sensory experiences by

which humans judge the existence of disease within themselveso Pain is the most common symptom of diseaseo Pain is one of the earliest signs of morbidity

Even if the main problem or disease does not manifest and is obvious, we experience this first.

The painful experiences of the sick pose problems in virtually every field of medicineo Pain can have structural basiso It can have an organic/underlying causeo Pain can appear to have little or no structural basis

Migraine or trigeminal neuralgiao Pain can be psychiatric

II. ANATOMY AND PHYSIOLOGY OF PAINA. Historical Perspective 2 major theories:

o Specificity Theory: Von Frey Skin consisted of a mosaic of discrete sensory spots that

give rise to one sensation when stimulated such as pain, pressure, warmth or cold

Example, on an area on the forearm, when a certain spot is stimulated would illicit sensation of pain, warmth or coldness. These discrete sensory spots would have a corresponding sensation when triggered

Each sensation has a distinct end-organ in the skin and each stimulus-specific end organ is connected to its own private pathway in the brain

o Pattern/Summation Theory: Also known as Intensivity Theory Goldscheider

Pressure spots could produce pain when sufficiently stimulated

There are no distinct pain receptors, but it’s the result of the summation of impulses such as the amount of pressure/force or thermal stimuli applied to the skin that will elicit the corresponding stimulus

Sensation of pain is the result of impulses excited by pressure or thermal stimuli applied to the skin

Head et al., 1905o Postulated the existence of 2 systems of cutaneous receptors

and conducting systems An ancient protopathic system

Sub-serving pain and extreme differences of temperature

Yielding ungraded diffuse impressions of an all-or-none type

More recently evolved epicritic system Mediated touch, two-point discrimination and lesser

differences of temperature, as well as localized pain “spinothalamic tract”

The pain and hyperesthesia that follow damage to a peripheral nerve were attributed to a loss of inhibition that was normally exerted by the epicritic upon the protopathic system

o Eventually lost credibility as findings could not be confirmed Melzack and Wall,1965

o Gate control theory of paino Observed in decerebrate and spinal cats:

Peripheral stimulation of large myelinated fibers (Aα/Aβ fibers) produced a (-) dorsal root potential

Stimulation of small (Unmyelinated) C (Pain) fibers caused a (+) positive root potential

These potentials which were a reflection of presynaptic inhibition or excitation, modulated the activity of secondary transmitting neurons (T cells) in the dorsal horn and that this modulation was mediated through inhibitory (I) cells.

Figure 1. – The Gate control theory of pain.

Trans Group: Joebeth Tabora, Nico Talento, Pamela Tan, Paul TanEdited By: Joseph Sta. Ana and Joy Rahayel

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Figure 2. – Role of Interneurons. There are interneurons that exist in between pathways. When you stimulate fibers, specific gates can open which will allow a stimulus to reach the brain thus pain would be felt.

(Stimulated) Large myelinated fibers -> Excite the I cells -> Presynaptic inhibition of the T cells -> Impulse will not reach the brain -> No pain sensation (Close gate)

(Stimulated) Small pain fibers -> inhibit I cells -> Excitation of T cells -> Impulse reaches the brain -> Pain is felt (Open gate)

Theory also gives emphasis that pain impulses from the dorsal horn must also be under the control of a descending system of fibers from the brainstem, thalamus, and limbic lobes

Gate control theory lost credibility because proponents cannot confirm theory due to some inaccuracy.

However this is still described and rationalized in the general framework of the oldest theory, that of specificity

B. Pain Receptors and Peripheral Afferent Pathways The sensory and motor fibers have been classified according to

their size and function: (See Appendix)

Figure 3. – Classification and function of sensory peripheral nerve fiber types and symptoms associated with intrinsic dysfunction of

each type. Focus more on A-delta and C fibers.

It is now well-established that 2 types of afferent fibers in the distal axons of primary sensory neurons respond maximally to nociceptive stimulio Very fine, unmyelinated, slowly conducting C fibero Thinly myelinated, more rapidly conducting A-d (A-delta) fiber

Peripheral terminations of both these primary pain afferents or receptors are the free, profusely branched nerve endings in the skin and other organso Covered by Schwann cells but contain little or no myelin

Table 1. – 3 Broad Categories of Free-Ending Receptors.

Receptors Stimulus Fiber Type

Mechanoreceptors

Activated by mechanical stimulation

A-d fibersC fibers

ThermoreceptorsActivated by thermal stimulation

C fibers

Polymodal nociceptors

Activated by noxious or tissue-damaging stimuli; can respond to mechanical and thermal stimuli

Also responds to chemical mediators

Majority are C fibersCertain A-d fibers respond to light touch, temperature, pressure and pain

Majority of C-fibers are polymodal and are most effectively excited by noxious or tissue-damaging stimulio Painful stimuli are translated in to electrical depolarization in

nerve endings are beginning to be understood.o When noxious stimuli activate a number of specialized

molecules -> will open cationic channels in membranes of nerve endings -> activates voltage gated sodium channels and generates an action potential in the sensory axon.

Figure 4. – Spinal cord in traverse section. This illustrates the course of the afferent fibers and the major descending pathways. Fast conducting pain fibers are not confined to the spinothalamic tract but are scattered diffusely in the anterolateral funiculus.

o The peripheral afferent pain fibers of both A-delta and C fibers have their cell bodies in the dorsal root ganglia (Interchangeable -> Dorsal horn = Posterior horn)

o Central extensions of these nerve cells project, via the dorsal root, to the dorsal horn of the spinal cord

The pain afferents, after travelling from the nerve endings, occupy mainly the lateral part of the root entry zone

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Figure 5. – Traverse section through a cervical segment of the spinal cord. (This illustrates the subdivision of the gray matter into laminae according to Rexed and the entry and termination of the main sensory fibers).

Figure 6. – Zona Terminalis or Tract of Lissauer.

Within the spinal cord, many of the C fibers form a discrete bundle called zona terminalis or the tract of Lissauero Predominantly a pain pathwayo Also contains deep sensory or propriospinal fibers

C. Dermatomal Distribution of Pain Fibers Each sensory unit is composed of:

o Sensory nerve cell in the DRGo Central and peripheral extensions o Cutaneous and visceral endings

Has a unique topography maintained throughout the sensory system from the periphery to the central cortex

Discrete segmental distribution of sensory units permits the construction of sensory maps

Figure 7. – Sensory Map. Each area is served by a specific unit.

Figure 8. – Topography of peripheral pathways and sensory levels.

o These areas of projection from visceral structures roughly correspond to the areas of adjacent root innervations, with some exceptions because of routing of sensory nerves to organs that migrate with development

D. Dorsal Horn After traversing the tract of Lissauer, the afferent pain fibers

terminate in the posterior gray matter or dorsal horn Reside predominantly in the marginal zone Most fibers terminate within the segment of their entry into the

cordo For example, all T1 fibers terminate at the T1 level, T2 fibers

on the T2 level but;o Some extend ipsilateral to 1 or 2 adjacent rostral and caudal

segments

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For example, some T1 fibers will go up to C8-C7 or some would go down to T2-T3 but mostly will terminate on the sensory level that is assigned to them

Some project to the contralateral dorsal horn via the anterior commissure but most of them will stay ipsilaterally

The 2nd order neurons are the sites of synapse of afferent sensory fibers in the dorsal horn

Arranged in a series of 6 layers or laminae called the Rexed laminae

Figure 9. – Rexed Lamina

Laminae I to IV: o Concerned with exteroceptive sensations

Laminae V and VI: o Concerned primarily with proprioceptive sensationso They also respond to cutaneous stimuli

Lamina VII: o Acts as a relay between midbrain and cerebellum

Lamina VIII: o Modulates motor activity, most probably via gamma motor

neurons (Not the concern of our topic) Lamina IX:

o Main motor area of the spinal cord Lamina X:

o Surrounds the central canal

Figure 10. – Rexed Laminae

Other cells that respond to cutaneous stimuli are located in Laminae VII and VIIIo The latter neurons are responsive to descending impulses from

brainstem nuclei as well as segmental sensory impulses From these cells of termination, second order neurons connect

with ventral and lateral horn cells in the same and adjacent spinal segments and subserve both somatic and autonomic reflexes

The main bundle of secondary neurons subserving pain sensation projects contralaterally (Also ipsilaterally) to higher levels o Remember, once the second order neurons are there in the

dorsal horn, most of the fibers cross contralaterally and then ascend towards the brain. They ascend towards the level of sensory unit and then they go up.

o Remember in the motor tract they cross at the level of the medulla but in spinothalamic tract, they cross at the level where they enter.

E. Neurotransmitters A-δ fibers

o Excitatory neurotransmitters Glutamate Aspartate

o Nucleotides ATP

C fiberso Substance P (Main NT and important in the management of

pain) Excites nociceptive dorsal root ganglion and dorsal horn

neurons Destruction produces analgesia Taking away substance P, the patient is pain free. Remember “Substance P-ain”

Opiateso Important modulators of pain as they are relayed through the

dorsal horn and through nuclei in the medulla and midbraino Noted to decrease substance P in the spinal cordo 3 types of opiate receptors:

Mu Delta Kappa

When activated, laminaI neurons release endogenous morphine-like peptides that bind specifically to opiate receptors and inhibit pain transmission at the dorsal horn levelo Enkephalinso Endorphins – make you happyo Dynorphins

Since they are endogenous, when the body feels pain, the body produces these substances so that without the use of external pain killers, the body would be able to relieve the pain.

III. SPINAL AFFERENT TRACTS FOR PAINA. Lateral Spinothalamic Tract Axons of 2° neurons that subserve pain sensation originate in

lamina I, II, V, VII and VIII of the spinal gray matter Principal bundle of axons decussates in the anterior commissure Ascends in the anterolateral fasciculus of opposite side of the

spinal cord as the spinothalamic tract to terminate in several brainstem and thalamic structures

Axons carrying pain impulses from each dermatome decussate 1-3 segments above the level of root entryo Discrete lesion of the lateral spinal cord creates a loss of pain

and thermal sensation of the contralateral trunko The dermatomal level of which is two to three segments

below that of the spinal cord lesion

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Figure 11. – Spinothalamic tract, the most important tract for pain.

As the ascending fibers cross the cord, they are added to the inner side of the spinothalamic tract o The longest fibers from the sacral segments come to lie most

superficiallyo Fibers from successively more rostral levels occupy

progressively deeper positionso Provides an explanation for “sacral sparing” of pain and

thermal sensation created by centrally placed lesions of the spinal cord

Figure 12. – As the ascending fibers cross the cord, they are added to the inner side of the spinothalamic tract.

IV. OTHER SPINOCEREBRAL AFFERENT TRACTSA. Spinoreticulothalamic or Paleospinothalamic Pathway

Projects directly to the reticular core of the medulla and midbrain Then to the medial and intralaminar nuclei of the thalamus

Figure 13. – The spinoreticulothalamic or paleospinothalamic pathway.

Spine reticular formation (midbrain) brainstem thalamus sensory cortex

More medially placed pathway in the anterolateral cord ascend to the brainstem reticular core via a series of short interneuronal linkso Unclear whether these are collateral vs. independent system

B. Direct Spinothalamic Pathway in the Anterolateral Fasciculus

Figure 14. – Direct spinothalamic pathway in the anterolateral fasciculus.

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Figure 15. – Pathways for visceral pain from the esophagus, stomach, small bowel and proximal colon are carried largely in CN X and

terminate in the nucleus of the solitary tract before projecting to the thalamus.

Figure 16. – Solitariothalamic tract.

V. THALAMIC TERMINUS OF PAIN FIBERS Spinoreticulothalamic fibers project onto the medial intralaminar

nuclei Projections from the dorsal column nuclei o Have a modulating influence on pain transmissiono Project to ventrobasal and ventroposterior group of nuclei

As the pathway ascends from peripheral nerve to spinal, medullary, mesencephalic, thalamic and limbic levels, the predictability of neuron responsivity to noxious stimuli diminishes

The direct spinothalamic fibers separate into 2 bundles as they approach the thalamus:o Lateral division

Terminates in the ventrobasal and posterior groups of nuclei VPL nucleus

o Medial division Terminates mainly in the intralaminar complex of nuclei

and nucleus submedius

Figure 17. – Parts of Thalamic Nuclei

A. Thalamocortical Projections Ventrobasal and ventroposterior group of nuclei project to 2 main

cortical areas:o Primary sensory cortexo Upper bank of the Sylvian fissure

Concerned primarily with the reception of tactile and proprioceptive stimuli and all discriminative sensory functions, including pain

The intralaminar nuclei:o Project to the hypothalamus, amygdaloid nuclei and limbic

cortexo Probably mediate the arousal and affective aspects of pain

and autonomic responses

Figure 18. – Thalamic nuclei and its corresponding cortical map. See appendix for larger picture.

The cortical representation in the sensory cortex correspond to the sensory homunculuso Allows for the accurate localization of the site of origin of a

painful stimulus

Figure 19. – Somatosensory map, sensory homunculus.

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System of descending fibers and way stations that modulate activity in nociceptive pathways

Endogenous pain control systemo Emanates from the frontal cortex and hypothalamus and

projects to cells in the periaqueductal region of the midbraino Passes to the ventromedial medullao Descends in the dorsal part of the lateral fasciculus of the spinal

cordo To lamina I, II, and V of the posterior horn

VI. PHYSIOLOGIC ASPECTS OF PAIN The stimuli that activate pain receptors vary from one tissue to

another With damage to tissue, there is release of proteolytic enzymeso Act locally on tissue proteins to liberate substances that excite

peripheral nociceptorso Ex. Histamine, prostaglandins, serotonin, K ions, kinins

Direct stimulation of nociceptors release polypeptide mediators that enhance pain perceptiono Ex. Substance P

Released from nerve endings of C fibers in the skin during peripheral nerve stimulation

Causes erythema by dilating cutaneous vessels and edema by releasing histamine from mast cells; also attracts chemoattractant for leukocytes

Called “neurogenic inflammation”

A. Perception of Pain Threshold for perception of pain o Lowest intensity of a stimulus recognized as pain o Approximately the same in all persons

Inflammation lowers the threshold for perception of pain by a process called “sensitization”o Allows ordinarily innocuous stimuli to produce pain in sensitized

tissues Pain threshold is raised by:o Local anestheticso Certain lesions of the nervous systemo Centrally acting analgesic drugs

Other mechanisms that alter the perception of pain:o Placeboo Acupunctureo Distraction and suggestiono Strong emotiono Manic stateso Depressiono Anxiety

The conscious awareness or perception of pain occurs only when pain impulses reach the thalamocortical level

Sensation, perception and the various conscious and unconscious responses to a pain stimulus comprise an indivisible process

Cerebral cortex governs the patient’s reaction to paino Also likely that the cortex can suppress or modify the

perception of pain

B. Endogenous Pain Control Mechanisms Discovery of a neuronal analgesia system that can be activated by

the administration of opiates or by naturally occurring brain substances that share the properties of opiates

In humans, electrical stimulation of the following sites produce analgesiao Midbrain periaqueductal gray mattero Rostroventral medulla

Nucleus raphe magnus Adjacent reticular formation

o Dorsolateral pontine tegmentum

Figure 20. – Descending Pathway Modulatory System.

Opiates also act pre and postsynaptically on the neurons of laminae I and V of the dorsal horn, suppressing afferent pain impulses from both the A-d and C fiberso Effects can be reversed by naloxone (Narcotic antagonist)

Naloxone can enhance clinical pain and interferes with the pain relief produced by placebos

These observations (On opiates and naloxone) suggest that the mysterious, beneficial effect of placebos (Also perhaps including acupuncture) may be a result of the activation of an endogenous system that shuts off the pain through the release of pain-relieving endogenous opioids, or endorphins o These are like the “morphine” within us

Activators of the endogenous pain control mechanismso Prolonged pain and fear – most powerfulo Stressful conditions

Endorphinso Endorphins are found in greatest concentration in relation to

opiate receptors in the midbraino At the level of the spinal cord, exclusively enkephalin receptors

are found b-endorphin Enkephalin Dynorphin

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Figure 21. – Mechanism of action of encephalin (Endorphin) and morphine in the transmission of pain impulses from the periphery to the CNS. Spinal interneurons containing enkephalin synapse with the terminals of pain fibers and inhibit the release of the presumptive transmitter, substance P. As a result, the receptor neuron in the dorsal horn receives less excitatory (Pain) impulses and transit fewer pain impulses to the brain. Morphine binds to unoccupied enkephalin receptors, mimicking the pain-suppressing effects of the opiate enkephalin.

Descending pain-control systems contain noradrenergic and serotonergic, as well as opiate links

Descending norepinephrine-containing pathwayo From locus ceruleus in the dorsolateral pons to the spinal cordo Activation blocks spinal nociceptive neurons

Rostroventral medulla contains a large number of serotonergic neurons from which descending fibers inhibit dorsal horn cells concerned with pain transmissiono Providing rationale for the use of certain antidepressant

medications (Serotonin agonists)

VII. CLINICAL AND PSYCHOLOGIC ASPECTS OF PAINA. Terminology

Figure 22. – Terms related to experience of altered sensations and pain. Please be familiar with them.

FROM 2015B: Hyperesthesia is a general term for heightened cutaneous

sensitivity Hyperalgesia refers to an increased sensitivity and a lower

threshold to painful stimuli Hyperpathia is a demonstrable reduction in pain perception

(e.g. Elevated threshold) associated with an increased reaction to the stimulus once it is perceived.o Although subtly different, Hyperpathia can be a type of

hyperalgesia according to Dra. Chua. Pallanesthesia - Loss of perception of vibration

o The mechanism of these abnormalities is not clear but both hyperpathia and allodynia are common features of neuropathic or neurogenic pain (e.g. Pain generated by peripheral neuropathy ) These features are exemplified by causalgia, a special type

of burning pain that results from interruption of a peripheral nerve.

B. Skin Pain and Deep SensibilityTwo types of skin pain: Pricking pain:

o Fast paino Evoked immediatelyo Transmitted by A-δ fibers

Stinging or burning pain:o Slow paino Follows in a second or twoo Transmitted by C fibers

Both types of dermal pain can be localized Constitute the “double response” of Lewis

o “Because there are A-δ fibers and C fibers in the skin, there is initial pain with slow pain that persists (Masakit na nga lalo pang sumakit)”

Compression of nerves by the application of a tourniquet to a limb abolishes pricking pain before burning pain because large fibers are more susceptible to pressure

Deep pain from visceral and skeletomuscular structures is basically aching in quality. (Cannot be localized, but pain is present)

If intense can be sharp and penetrating (Knife-like) o We are able to distinguish visceral pain, wherein one may not

be able to localize the pain, from cutaneous pain, which is easier to localize.

Visceral pain produces 2 additional sensationso Referred Hyperalgesia

Tenderness at remote superficial siteso Visceral Hyperalgesia

Enhanced pain sensitivity in the same and nearby organs Because somatic and visceral sensibility may overlap

(Overlap in sensory levels)

VISCERAL PAIN Deep Diffuse and poorly localized Margins of the painful zone are not well delineated

o Because of the relative paucity of nerve endings in viscera compared to the skin

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C. Referred pain Deep pain has indefinite boundaries

o Location is distant from the visceral structure involvedo Tends to be referred not to the skin overlying the viscera but

to other areas of skin innervated by the spinal segment or segments

o Examples: There are times that chest pains (Myocardial infarction) have referred pain to shoulder and jaw while patients with cholecystitis or gall bladder disease may have referred pain to right shoulder or right upper back.

FROM 2015B:Referred Pain: Pain projected at a site distant from the source

o Example. Afferent fibers from cardiac structures (T1-T4) Chest pain can go as far as the inner side of arm, because

of T1-T4 involvemento Take note: Small caliber pain afferents from deep structures

project to a wide range of Lamina V neurons in the dorsal horn, as do cutaneous afferents.

o This phenomenon can be further explained by the convergence of deep and cutaneous afferents on the same dorsal horn cells, coupled with the fact that cutaneous afferents are more numerous than visceral afferents and have direct connections with the thalamus.

The nociceptive receptors and nerves of any given visceral or skeletal structure may project upon the dorsal horns of several adjacent spinal or brainstem segments the pain from these structures may be fairly widely distributed

Sclerotomes: o Regions of projection of pain that originates in the bones and

adjacent ligamentous structureso Although dermatomes and sclerotomes overlap, the precise

patterns are slightly different Aberrant Reference:

o Phenomenon explained by an alteration of the physiologic status of the pools of neurons in adjacent segments of the spinal cord. For example, cervical arthritis or gallbladder disease,

causing low-grade discomfort by constantly activating their particular segmental neurons, may induce a shift of cardiac pain from its usual locale to either cephalad or caudad

o Once it becomes chronic, any pain may spread quite widely in a vertical direction on one side of the body.

D. Chronic Pain One of the most perplexing issues in the study of pain is the

manner in which chronic pain syndromes arise Theories:

o 1st: In an injured nerve, the unmyelinated sprouts of A fibers and C-fibers become capable of spontaneous ectopic excitation and after discharge and susceptible to ephaptic activation (Nerve-to-nerve cross activation) The injured nerve, even without stimulation, can produce

its own excitation to elicit pain stimulus.o 2nd: These injured nerves are also sensitive to locally applied or

intravenously administered catecholamines because of an overabundance of adrenergic receptors on the regenerating fibers (May be a basis for causalgia)

In Peripheral nerve injury wherein the body tries to heal itself, will produce nerve endings in the process but unfortunately when healing is aberrant, will lead to abundance of receptors that are more sensitive to pain or painful stimulus.

Excites spontaneously with overabundance of receptors, causes continuous or vicious cycle of pain

Central sensory structures o (e.g. Sensory neurons in the dorsal horns of the spinal cord or

thalamus) o If chronically bombarded with pain impulses, may become

autonomously overactive (Being maintained in this state perhaps by excitatory amino acids) and may remain so even after the peripheral pathways have been interrupted.

o Example: Phantom limb in an amputated diabetic foot Peripheral nerve lesions have been shown to induce enduring

derangements of central (Spinal cord) processingo Example: Avulsion of nerves or nerve roots may cause chronic

pain even in analgesic zones (Anesthesia dolorosa or “de-afferentation pain”) The nerve is injured thus the sensation is less, but there is

still a complaint of pain.o Painful states such as causalgia, spinal cord pain, and phantom

pain are not abolished simply by cutting spinal nerves or spinal tracts. (Abnormal discharge subsides in the spinal cord which had been cut), but is still recorded in thalamus

None of these phenomena can adequately explain the entire story of chronic pain.

Structural changes in the cord are suspected to be able to produce persistent stimulation of pain pathways

Singular attributes of paino It does not appear to be subject to negative adaptation

Pain may persist as long as the stimulus is operative (It does not adapt)

o Prolonged stimulation of pain receptors sensitizes them, so that they become responsive to even low grades of stimulation, even to touch Allodynia - even if the stimulus is then normal, it is felt as

painful due to previous sensitization In pain continuous stimulation causes overstimulation,

“lalong sasakit”

E. Emotional Reaction to Pain Another remarkable characteristic of pain is the strong feeling or

affect with which it is endowed, nearly always unpleasant Since pain embodies this element, psychologic conditions assume

great importance in all persistent painful states

VIII. APPROACH TO THE PATIENT WITH PAIN AS THE PREDOMINANT SYMPTOM

Whenever pain appears to be abnormal or when it constitutes the chief complaint or one of the principal symptoms, the physician must attempt to reach a tentative decision as to its mechanism and cause seek out the main characteristics of the pain in terms of the following:

1) Location2) Mode of onset3) Associated features4) Quality and time-intensity attributes5) Duration6) Severity7) Provoking and relieving factors

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Some physicians find it helpful, particularly in gauging the effects of analgesic agents, to use a “pain scale” have the patient rate the intensity of his pain on a scale of zero (no pain) to ten (worst pain) or to mark it on a line.

Figure 23. –Pain Scale

Once the pains due to the more common and readily recognized diseases of each organ system are eliminated, there remain a significant number of chronic pains that fall into one of four categories:

1. Pain from an obscure medical disease, the nature of which has not yet been disclosed by diagnostic procedures (Usually found in connective tissue diseases or neurologic diseases such as multiple sclerosis)

2. Pain associated with disease of the central or peripheral nervous system (Example: neurogenic or neuropathic pain)

3. Pain associated with psychiatric disease4. Pain of unknown cause.

A. Pain due to Undiagnosed Medical Disease Source of the pain is usually in a bodily organ and is caused by a

lesion that irritates and destroys nerve endings. The term nociceptive pain is often used, but it is ambiguous.

o It usually means an involvement of structures bearing the termination of pain fibers.

o Carcinomatosis is the most frequent example

B. Neurogenic or Neuropathic Pain Used interchangeably to designate pain that arises from direct

stimulation of nervous tissue itself, central or peripheralo Exclusive of pain due to stimulation of sensitized C fibers by

lesions of other bodily structureso In nerve endings, there is neuropathic pain

Comprises a variety of disorders involving:o Single and multiple nerves, notably trigeminal neuralgia and

those due to herpes zoster, diabetes, and trauma (Includes causalgia)

o Polyneuropathies of diverse type;o Root irritation (Prolapsed disc)o Spinal arachnoiditiso Spinal cord injurieso The thalamic pain syndrome of Dejerine-Roussy;o Rarely parietal lobe infarction

As a rule, lesions of the cerebral cortex and white matter are associated not with pain but with hypoalgesia

Difference between Neuropathic and Neuralgia:o Neuropathic – with disease of peripheral nerve

o Neuralgia – no obvious disease of peripheral nerve o Example:

In trigeminal neuralgia, it was called neuralgia because trigeminal nerve is not abnormal in MRI.

In diabetic neuropathy, it was called neuropathy since distal most nerve endings are damaged by hyperglycemia, immune conditions etc.

C. Peripheral Nerve Pain Painful states are in most cases related to disease of the

peripheral nerveso It is pain from this source that the term neuropathic is more

strictly applicable.o Ex. Diabetic polyneuropathy

When the disease of the nerve are undetectable by standard tests.o the term neuralgia is preferredo Ex. Trigeminal neuralgia

Postulated mechanisms of peripheral nerve pain: o Denervation hypersensitivity:

When a group of neurons is deprived of its natural innervation, they become hyperactive

o Reduced density of certain types of fibers in nerves supplying a causalgic zone as the basis of the burning pain Comparison is not consistently different

o The occurrence of ectopic impulse generation all along the surface of injured axons and the possibility of ephaptic (passage of a neural impulse from one nerve fiber, axon or dendrite to another through the membrane) activation of unsheathed axons seems applicable particularly to some causalgic states A damaged nerve is capable of spontaneous excitation

leading to more paino The sprouting of adrenergic sympathetic axons in response to

nerve injury is an ostensible explanation for the abolition of causalgic pain by sympathetic blockade.

o Regenerating axonal sprouts, as in a neuroma, are also hypersensitive to mechanical stimuli. On a molecular level, it has been shown that sodium

channels accumulate at the site of a neuroma and all along the axon after nerve injury, and that this gives rise to ectopic and spontaneous activity of the sensory nerve cell and its axon.

C. Causalgia and Reflex Sympathetic Dystrophy (Complex Regional Pain Syndrome) The term causalgia is best reserved for the syndrome described

o Persistent burning pain and abnormalities of sympathetic innervation consequent upon trauma to a major nerve in an extremity.

Complex regional pain syndromeo Wide range of conditions that are characterized by persistent

burning pain but have only an inconstant association with sudomotor, vasomotor, and trophic changes and an unpredictable response to sympathetic blockade.

o may follow non-traumatic lesions of the peripheral nerves or even lesions of the CNS (Mimocausalgia)

D. Central Neurogenic Pain In central lesions, de-afferentation of secondary neurons in the

posterior horns or of sensory ganglion cells that terminate on

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them may cause the de-afferented cells to become continuously active and, if stimulated by a microelectrode, to reproduce pain.o In patients whose spinal cords have been transected, there

may be intolerable pains felt below the level of the lesion. In the rare cases of intractable pain with lateral medullary or

pontine lesions, loss of the descending inhibitory systems seems a likely explanation.

E. Pain in association with Psychiatric Diseases It is not unusual for patients with endogenous depression to have

pain as the predominant symptom. Most patients with chronic pain of all types are depressed. It’s perplexing because it does not respond to usual pain

medications. It is safe to assume that all patients with chronic pain have an associated depression and those who have depression have some sort of chronic pain (as a symptom of their depression)

F. Chronic Pain of Indeterminate cause This is the most difficult, most perplexing group of all because you

keep asking yourself, ano ba ito, saan ba nanggagaling ito pain in the thorax, abdomen, flank, back, face, or other part that

cannot be traced to any visceral abnormality. Supposedly all neurologic sources have been excluded by repeated

examinations and imaging procedures. Yet the patient complains continuously of pain, is disabled, and

spends a great deal of effort and money seeking medical aid. Look for a psychologic aspect to that, maybe it’s psychosomatic pain.

G. Rare and Unusual Disturbances of Pain Perception Pain hemiagnosia Congenital insensitivity to pain Universal analgesia - congenital Riley-Day syndrome (Congenital dysautonomia) Asymbolia for pain(just sensation)

IX. TREATMENT OF INTRACTABLE PAIN Once the nature of the patient’s pain and underlying disease has

been determined, therapy must include some type of pain control. Attention is directed to the underlying disease, with the idea of

eliminating the source of the pain by appropriate medical, surgical, or radiotherapeutic measures.

The difference b/w nociceptive and neuropathic pain, for nociceptive pain, you usually start with simple analgesics, non-opiate analgesics like, Aspirin, Paracetamol, other NSAIDs. Then later on, if they are not responding to these, then you can try the narcotic analgesics.

When pain cannot be relieved:o Attempt to use the milder measures for pain relief first

Example: Non-narcotic analgesics and antidepressants or anticonvulsants

o Narcoticso Local nerve blockso Surgical approaches for pain relief.

The rule of thumb is, you start with milder analgesics and if the pain is controlled, you maintain the patient on those. But for example on cancer pain, you know that paracetamol won’t work so much,so you either combine Tramadol with Paracetamol or you give something that is more potent analgesic singly. If the patient still complains of pain, in the Ph we have, oxycodone, morphine, meperidine and fentanyl.

Recap: what do you give a cancer patient who is having multiple episodes of vomiting and is complaining of pain? Fentanyl. Because it’s a transdermal patch.

*Please refer to appendix for Table 8-3: Common drugs for the management of chronic pain

X. SUPPLEMENTAL MEDICATIONS FOR THE TREATMENT OF PAIN For neuropathic pain, antiepileptic agents like CBZ, Valproate,

Gabapentin, Pregabalin or the antidepressants that work on serotonin and noradrenergic receptors like SSRIs (Sertraline), SNRI (Duloxetine) and TCAs (good for both pain and mood disorders for chronic pain)

Tricyclic antidepressants, especially the methylated forms (Imipramine, amitriptyline, and doxepin) o Works on the serotonin and noradrenergic systemo Block serotonin reuptakeo Enhances the action of serotonin at synapseso Facilitate the action of the intrinsic opiate analgesic system.

(Remember your descending pain modulation system) Anticonvulsants have a beneficial effect on many central and

peripheral neuropathic pain syndromeso Generally less effective for causalgic pain due to partial injury

of a peripheral nerveo Blocking of excess sodium channels (MOA of CBZ, Phenytoin,

Valproate) reduces evoked and spontaneous activity in nerve fibers

o In Trigeminal Neuralgia, DOC is CARBAMAZEPINE (CBZ); you don’t proceed at once to morphine. There is a systematic way of managing pain.

Most often, a combination of medications is used for the treatment of intractable chronic paino Ex. Gabapentin + Morphine; Pregabalin + Tramadol; Pregabalin

+ CBZ Try to augment the effects of different drug groups and do

not choose two medications from the same category. Example, using an anti-convulsant with an opioid analgesic gives better results

XI. TREATMENT OF NEUROPATHIC PAIN Antiepileptic drugs Topical

o Capsaicin creamo EMLA

Spinal injections- for chronic lumbosacral radiculopathyo Epidural blockso Root blockso Facet blocks

Injections- for severe myofascial (ie. Nodules) pains, or for those severely contracted, some doctors inject steroids directly to the belly of the muscle to relax it o Steroidso Steroids + analgesics

Intravenous infusionso Lidocaineo Mexiletine

Direct injection of the sympathetic ganglia in affected regions of the body-reserved for extreme forms of pain o Regional intravenous infusion of sympathetic-blocking drug

(Bretylium, guanethidine, reserpine) into a limb that is isolated from the systemic circulation by use of tourniquet

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Example: A Bier block

XII. TREATMENT OF REFLEX SYMPATHETIC DYSTROPHY Use of bisphosphonates Electrical stimulation of the posterior columns of the spinal cord Epidural infusion of drugs such as ketamine

XIII. ABLATIVE SURGERY IN THE CONTROL OF PAIN(According to Dra, these are not usually done)

The least destructive procedure consists of surgical exploration for a neuroma if a prior injury or operation may have partially sectioned a peripheral nerve

Implantation of a spinal electrical stimulator, usually adjacent to the posterior columns

Spinothalamic tractotomy, in which the anterior half of the spinal cord on one side is sectioned at an upper thoracic level, effectively relieves pain in the opposite leg and lower trunk

Bilateral tractotomy is also feasible, but with greater risk of loss of sphincteric control and, at higher levels, of respiratory paralysis.

Pain in the arm, shoulder, and neck is more difficult to relieve surgicallyo High cervical transcutaneous cordotomyo Commissural myelotomy by longitudinal incision of the

anterior or posterior commissure of the spinal cord over many segments

o Lateral medullary tractotomy – abandoned by neurosurgeons

o Lateral mesencephalic tractotomy – abandoned by neurosurgeons

Stereotactic surgery on the thalamus for one-sided chronic paino Unpredictable

Cortical ablationso Unpredictable

XIV. NON-MEDICAL METHODS FOR THE TREATMENT OF PAIN Biofeedback and Meditation are examples of psychotherapies Imagery Acupuncture Some forms of spinal manipulation Transcutaneous electrical stimulation

Dra. Chua said Study Chapter 8; it’s all there. But for the interest of time, just study this trans

XV. APPENDIX

Figure 3. – Classification and function of sensory peripheral nerve fiber types and symptoms associated with intrinsic dysfunction of each type. Focus more on A-delta and C fibers.

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Figure 18. – Thalamic nuclei and its corresponding cortical map.

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The WHO has stepwise approach to pain management. We start off with Simple analgesics like Paracetamol, Ibuprofen, if not totally controlled, you can step up, give NSAIDS, and tramadol, and so that he highest level will be Opiates”

Always start with Non opioid analgesics, but before starting we have to figure out if it is NOCICEPTIVE or NEUROPATHIC. Because the medications that act on neuropathic pain are different from those that act in nociceptive pain.

If this is NOCICEPTIVE pain, you can start with Non opioid and opioid analgesics. If pain control is inadequate you can shift to Narcotic analgesics.

Antiepileptic drugs are usually reserved for neuropathic pain.”

Editor’s note: The trans last year contained computations for the drug dosages. We have chosen not to include them as they were not discussed by the current lecturer.

Neurology II 2.07 Pain Dr. Camara Chua[1]

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