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nCorresponding auMedellin, Colombia

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Interventional pain management for phantom limb pain:An algorithmic approach

Santiago Jaramillo, MDa,d,n, Lizeth Jazmin Ramirez, MDe,Carlos Eduardo Restrepo-Garces, MDa,c, Carlos Mario Gómez B, MDa,c,Juan Felipe Vargas Silva, MDa,b,c

aDepartment of Surgery & Image Guided Therapy, Pain Clinic, Hospital Pablo Tobon Uribe, Calle 78 B 69-240, Medellin, ColombiabFellowship Pain Medicine & Palliative care Fundación, Bogota, ColombiacDepartment of Anesthesia, Pain Relief Unit, Clinica Las Americas, Medellin, ColombiadPain Clinic, Clinica del Campestre, Medellin, ColombiaeDepartment of Surgery & Oncology, Pain Clinic & Palliative Care Unit, Hospital Pablo Tobon Uribe, Medellin, Colombia

a r t i c l e i n f o

Keywords:

Phantom pain

Interventional pain

nt matter & 2013 Publish1053/j.trap.2013.08.007

thor at: Department of Su.mdsanti@hotmail.com (S

a b s t r a c t

Phantom limb pain is a type of chronic pain existing in different organs, not just limbs. The

incidence is very high in the postamputation period and treatment can be a challenge. The

pharmaceutical treatment strategies in addition to psychological rehabilitative strategies

and interventional management play a successful role in the management of these

patients. For this article, we conducted a review of literature about pain management for

phantom limb pain to identify the treatment modalities, which involved interventional

pain management, and an algorithmic approach is proposed.

& 2013 Published by Elsevier Inc.

Introduction

Phantom limb pain continues to be a challenge for every paindoctor. As we all know, this type of chronic pain can berefractory to multiple forms of treatments, therefore it isfrustrating for the lack of life in our patients. A lot of work hasbeen done trying to understand the causes of this complexsymptom and how to face it in a clinical setting. Amputatedpatients suffer a lot, and we are committed to giving them thebest treatment available.Historically, more than 4 centuries have passed since the

outstanding French surgeon Dr Ambroise Paré wrote theclinical description of this entity,1 and it is sad to recognizethat after all this time we do not have all the answers for thebest treatment yet.The classification is not universally accepted as different

terms in the literature exist.2 Probably this deserves moreattention to differentiate, in a definitive way, the pathologies

ed by Elsevier Inc.

rgery & Image Guided Th

. Jaramillo).

that fit this diagnosis to choose the appropriate individual-ized treatment. There is sufficient information about theexistence of phantom symptoms in different organs, andnot just limbs, such as the eyes, breast, penis, and rectum,among others.

Terminology

The term phantom pain (PhP) refers to pain perceived by theregion of the body no longer present, which usually manifestsas burning, throbbing, aching, cramping, stabbing, etc.,whereas the term phantom sensations refers to nonpainfulsensations that typically manifest as kinetic, kinesthetic, orexteroceptive perceptions.3 Telescoping is the progressivenonpainful perception of shortening of the phantom. Stumppain, which is often called residual limb pain (RLP), is painlocalized in the residual portion of the limb.4

erapy, Pain Clinic, Hospital Pablo Tobon Uribe, Calle 78 B 69-240,

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Incidence

The incidence of phantom sensations is very high in thepostamputation period, which varies between 85% and 98%among the amputees, and gradually diminishes over time,resolving in most patients 2-3 years later.5 Most authors agreethat PhP has an incidence of 50%-80%, and RLP is reported inmore than 50% of the amputees.5-8

Mechanism

Multiple theories have been elucidated about the origin anddevelopment of PhP. All of them try to explain the differentclinical manifestations of this pathology, but none canexplain all the symptoms and specific cases. Three differentmechanisms are proposed: central, peripheral, and psycho-logical.8 It is probably the combination of these factors that inone way or another permits the development of the diseaseand its expression.

Peripheral mechanisms

These occur as the result of the traumatic tissue process thatlead to amputation and include the development of neuro-mas and their ectopic discharges, sympathetic nervous sys-tem dysfunction, neural excitability, etc., which contribute tothe development of PhP and RLP.8,9

Central mechanisms

As a result of the amputation, structural changes in thespinal cord that lead to central sensitization (increasedexcitability of dorsal horn neurons, reduction of inhibitoryprocesses, and structural changes at the central nerve end-ings of the primary sensory neurons) occur, leading tochanges in the perception of the whole body at the brainstem, thalamus, and the cortex. This, as Dr Melzack suggests,can alter the normal function of the “neuromatrix” (thesupposed anatomical substrate of the self), which in turnchanges his or her own expression, known as the neuro-signature. This altered process leads finally to the phantomperception.8-10

Another possible central explanation for PhP and sensa-tions is the development, because of the structural changesassociated to the amputation, of a reorganization of theprimary somatosensory cortex, and the thalamus, with thecoverage of the “missing” part of the body by neighboringneurons disturbing the normal perception of the body.8

Psychological mechanisms

It is not a secret that the psychological effect in amputees isdirectly related with the cause of the amputation. Amputa-tions in ischemic and neoplastic diseases give time forpsychological preparation, and probably are part of the “hopeof life” of the patient, whereas traumatic amputations do not.It also has been demonstrated that stress exacerbates PhPepisodes.8

Clinical pearls

PhP and RLP are cataloged as neuropathic, but it is important tocorrectly analyze the entire spectrum of complaints in everypatient, because it is not unusual to find somatic pain compo-nents in them, which may be related to multiple treatments,such as surgeries, infection, hematomas, adaptation programs(overload of other structures, back, and hip), etc.As noted before, PhP has to be ruled out since the beginning

of the amputation. Look for complaints in the amputatedlimb disturbing the patient, and those that are usually relatedto neuropathic symptoms. Residual pain should be differ-entiated from phantom limb pain because the latter hasbetter possibilities for interventional pain management, asdiscussed later.Try to find any stump characteristic that makes you suspi-

cious of sympathetic nervous system malfunction (allodynia,edema, color change, hyperhidrosis, etc.), as this opensthe possibility of occurrence of sympathetic blocks in yourpatient.Tender points or nodules around the stump that can be

related with neuromas should be observed.It should be kept in mind that PhP and RLP can also be

described in other missing parts of the body, but limbs, suchas the eyes, breast, penis, tongue, teeth, and rectum. More-over, other causes of this kind of pain owing to other factors(radiculopathies, neuropathies, infection (herpes zoster),ischemia, tumor invasion, etc.) have to be excluded.11

Treatment

Multiple medications have been tried for PhP and RLP, and itis important to offer medications of different pharmacologicgroups. The medications should be titrated and patientshould be followed up closely, giving enough time for doseor medication changes, knowing that in neuropathic pain theresponse is usually slow.Combination of drugs is usually the norm, and one has to

be alert for adverse reactions and its adequate management.Even if a great job is done, some studies suggest than lessthan 10% of the patients would be benefited.12

Preemptive analgesia and anesthesia, including epidural orperipheral nerve block, have not been proven as definitivemeasures for prevention of PhP or RLP, but are part of theroutine management of the acute pain patient and have to bealways kept in mind.Common analgesics, acetaminophen, and nonsteroidal

anti-inflammatory drugs are the most commonly prescribedmedications for PhP,13 but with poor results owing to limi-tation in analgesic potencies and side effects.The most prescribed medications for neuropathic pain in

both groups (PhP and RLP) are antidepressants and anticon-vulsants.5 There are multiple studies that show a goodresponse of these medications in neuropathic pain patholo-gies, but not specific for PhP and RLP. Tricyclic antidepres-sants (amitriptyline and nortriptyline) should be tried ifburning, lancinating, or cutting pain is present,14 or anticon-vulsants should be tried if shocking or electric pain is mostly

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present (carbamazepine, gabapentin, oxcarbazepine, and pre-gabalin).15-17

Opioids (oxycodone, methadone, morphine, and levorphanol)are the gold standard in pain management and have beenshown to have a good profile in pain control. Some studiessuggest a role in diminishing cortical reorganization, which is apossible advantage over other therapeutic groups.18

Other medications with anecdotal but inconsistent thera-peutic effects are N-methyl-D-aspartate antagonists (ketamineand memantine),19,20 calcium channel blockers (nifedipine),β-blockers (propranolol), and calcitonin.

Interventional pain management

There have been multiple interventional treatments offeredto patients with PhP and RLP, most of them with greatanecdotic responses but hard to reproduce in differentpatients.It is very important to classify patients according to

symptoms and physical examination.An algorithm of procedures is suggested, but is important

to note that there is no sufficient grade of evidence to giveopen recommendations, so these are the conclusions of theauthors based on an extended review of the literature.If the patient has evidence of neuromas on physical

examination, try to perform a block with ultrasound (US) asa diagnostic measure.21 It should be noted that on US, theyappear as hypoechoic masses, and the block has to bereproduced twice to eliminate placebo responses.21-23 If apositive response is obtained, and short relief is acquired,consider doing a neurolytic procedure on the nerve.At our institution, pulsed-radiofrequency ablation is the

preferred method over chemical neurolysis in patients with

Fig. 1 – Algorithmic approach. PhP, phantom pain; RLP, residualresponse.

neuroma related to stump pain. The lesion can be perpen-dicular after a concordant sensory stimulation.24 The timecan be titrated from 2-6 minutes. Performing multiple lesionsmay improve the outcome, but there is no trial supporting ordenying this approach. Other techniques used with goodreports are cryotherapy and chemical neurolysis.25,26

If short-term relief is obtained and the patient is still havingmoderate to severe pain, and no contraindications are found,consider peripheral nerve stimulation (PNS)27 or spinal cordstimulation (SCS), depending on the complexity of the caseand the number of nerves involved. PNS appears to be abetter option if 1 or 2 nerves are involved. The advantage isalways the possibility of having a preimplantation test. If youchoose PNS, US can be helpful in finding the nerve andavoiding surgical dissections at the stump.27

SCS has been used for PhP since 1970. Technologicaladvancement has permitted the development of more flexi-ble and easy to implant systems. Studies have shown initialgood results, but around 30% report good long-term paincontrol in recent studies.28-30 This decision has to be individ-ualized for each patient and depends on the health politics ofevery country or institution.If the patient has a compromised autonomic nervous

system at the stump, consider doing sympathetic nerveblocks, because some patients would benefit, especiallythose with a concomitant complex regional pain syn-drome.31,32 If short relief is obtained, thermal sympathectomycan help in having long-term resolution of pain, but if painreappears quickly after these, SCS vs PNS trial can be theanswer.For those refractory patients to interventional pain meas-

ures, and good response to pain management with opioids,but remarkable side effects, intrathecal morphine or bupre-norphine can be the answer.32,33

limb pain; LTR, long-term response; STR, short-term

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Finally in those patients with severe pain, refractory to allmeasures, the last option would be deep brain stimulation,with long-term relief in more than 25%,34 or motor cortexstimulation,35,36 applied at some specific centers.In Figure, we summarized the actual algorithm used in our

Hospital.

Conclusions

PhP and RLP remain refractory to multiple types of treat-ments. Patients suffer as a consequence of these diseases,and as in most chronic pain patients, most of them remainunder treated and isolated. Interventional pain managementis an alternative for some of them, although it is not statisti-cally proven. Interventional treatments have to be offered inwell-selected patients, and in the future, we hope to havedefinitive answers for PhP and RLP prevention, as this is thecritical stage to limit the development of central pain.

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