Pain Management in the Amputee

Christopher A. Hinnant, MD Physical Medicine & Rehabilitation Laguna Honda Hospital & Rehabilitation Center San Francisco, California

History of Phantom Limb Pain

First described in 1552 by Ambroise Par

-"the patients who have, many months after cutting away of the leg, grievously complained that they still felt great pain of the leg so cut off. . . the patients imagine they have their members yet entire

History of Phantom Limb Pain

Herman Melville immortalized phantom limb pain in American literature, with graphic descriptions of Captain Ahabs phantom limb in Moby-Dick "A dismasted man never entirely loses the feeling of his old spar. . . And I still feel the smart of my crushed leg, though it be now so long dissolved"

History of Phantom Limb Pain

Phantom limb pain was not formally recognized in the medical community until a Mayo Clinic study of 1941 Index Medicus recognized this term in 1954

Besides the limbs, painful phantoms have been described for eyes, nose, teeth, tongue, breast, bladder, testicle & penis

Amputation Statistics

200,000 Surgical Amputations performed per year in the U.S. 1.7 million people living with limb loss (Ziegler-Graham 2008) It is estimated that one out of every 200 people in the U.S. has had an amputation (Adams) Pain is the most common complaint after amputation

Amputation Statistics
82% of amputations are dysvascular 97% of lower limb amputations are dysvascular 69% of all traumatic amputations are in upper limb

Prevalence of Pain Symptoms

Immediately post-op, PLP= 72% (& PLS= 84%) After 6 months, PLP= 67% (& PLS= 90%) After one year, PLP= 61% After two years, PLP= 59%
After one month, RLP= 72% After 13 months, RLP= 13% (Cascale)

Prevalence of Pain Symptoms

PLP in 0.5% to 100%, but most sources use 50-85%

Usually intermittent & of moderate intensity (VAS average = 5)

RLP in 100% post op, but decreases with time to 10 to 25% range (Ehde)

Amputee Pain- Severity

48% experienced pain a few times per day or more (Kooijman) A quarter of those with pain reported their pain to be extremely bothersome (Ephraim) Sofor most, the pain is episodic and not particularly disabling, but for a subset of patients, can be quite severe(Ehde)

Amputee Pain- Evaluation

Good history Thorough physical examination Appropriate Tests Resist the initial tendency to consider all pain as being phantom pain Amputee Pain can be of different etiologies Amputation is not a static condition progressive deteriorating condition affecting the health of the amputee over time Understand pain impact on function

Residual Limb Pain

Pain affecting and originating in the residual portion of the limb

Residual Limb Pain

Residual Limb Pain Etiologies

Neuroma Prosthetic Fit Issues Scarring and Healing Issues Orthopaedic Problems
Bony Overgrowth Osteomyelitis Stress Fracture Arthritis

Trophic Skin Changes Tumor Recurrence

Cellulitis Folliculitis

Residual Limb Pain

Early complications Dehiscence Superficial infection Deep infection Infection can also present late with residual limb osteomyelitis having an average time between amputation and diagnosis of187 days RLO should be considered when delayed wound healing or residual limb pain (Smith)

RLP- Neuromas

Develop in all residual limbs after amputation Problematic when entrapped in scar tissue or in position where they are exposed to external mechanical loading Neuropathic lancinating pain
Manual palpation Socket pressure Traction of adherent scar tissue Tinels sign

RLP- Neuromas Treatment

Socket modification Gel socks, liners, redistribute loads, reduce shear pressures Local anesthetic / steroid injection Resection of Neuroma
therapeutic and diagnostic
neuroma moved to a deeper site or by placing the end of nerve in bone Can reform and become symptomatic

RLP- Bone Issues

Use of a prosthesis can place more strain on the joints proximal to the amputation contributing to arthritis pain Treatment algorithms for non-amputees should be used to maintain function in prosthesis users (NSAIDs, intraarticular steroids, THA, TKA, etc.) Knee osteoarthritis may be partially relieved by the addition of knee joint & thigh corset to allow shared weight bearing between the residual limb and the thigh
hips, knees, shoulder

RLP- Bone Issues

Terminal overgrowth of bone mostly in skeletally immature 4-35% in peds amputations Case reports of bone overgrowth in adults (Dudek) Most often in traumatic amputations in peds & only cases in adults were also due to trauma Distal stump pain & tenderness, tissue compression, bursa formation, skin ulceration X-ray diagnosis (& by exam) Treatment Socket modification Surgical resection of bone

RLP- Bone Issues

Heterotopic Ossification More common in traumatic/combat (63%) Most often in blast injuries or with amputations performed at the zone of injury Most are asymptomatic When painful and refractory surgical excision (Potter)

RLP- Bone Issues

Fractures of residual limb Decreased bone density in residual limb (Sherk) Hip & distal portion most common sites (Sherk) Overall incidence is 3% in LE amputees (Denton) Fall while wearing the prosthesis is the most mechanism of injury

RLP- Tumor Recurrence

Suspect when late pain occurs in a limb amputated because of tumor Local recurrence is a possibility

RLP- Dermatologic Disorders

Prevalence 30-50% Most often related to prosthesis fit Hyperhidrosis, contact dermatitis, cellulitis, folliculitis, epidermal cysts, dermal granulomas Round or oval swellings deep within the skin The skin may break down and erode or ulcerate

Phantom Limb Sensation

Awareness of non-painful sensation in the amputated part of a limb Resembles the somatosensory experience of the physical limb before amputation Phantom limb sensations 90-98% in immediate post-op period Typically is more intense in the early stages after amputation and can gradually fade with time
warmth, itching, sense of position, and mild squeezing

PLS prevalence later on is 54-87%

The more distal segments (toes etc.) tend to present the most vivid sensations In some cases the symptoms persist treatment is not typically required (nonpainful)

Phantom Limb Pain

Pain perceived in the amputated portion of the extremity Described as burning sensation, cramp, stabbing, squeezing, prickling, shooting Phantom Posture
Painful contortions of the limb Clenched fist Spasm Fingernails digging into palm

Phantom Limb Pain

PLP- Pathophysiology

Not completely understood Categories of theories Peripheral and spinal sensitization Cortical neuronal rearrangements Cortical reorganization & neuroplasticity most commonly cited Deafferented cortical areas representing the amputated limb are taken over by neighboring representational zones in both primary somatosensory cortex & motor cortex Not great improvements in our understanding in the nearly 450 years its been described

PLP- Pathophysiology

Maladaptive cortical remapping so that some low threshold touch input might cross-activate high threshold pain neurons Pathological remapping can lead to chaotic output which might be interpreted as either paresthesias or pain by higher brain centers The mismatch between motor commands and the expected, but missing, visual and proprioceptive input may be perceived as pain The tendency for the pre-amputation pain whether brief (e.g. a grenade blast, car accident) or chronic (cancer) to persist as a memory in the phantom

PLP- Pathophysiology

Phantom limb pain and cortical re-organization are positively related

Case series 13; upper limb amputees 8 had PLP and 5 did not Functional neuroimaging Subjects with PLP had 5x more extensive cortical reorganization than those without PLP Severity of PLP correlated with degree of cortical re-organization (r=.93, p<.0001) (Flor)

Telescoping phantoms with increased pain lead to greater cortical reorganization (Karl)

PLP- Treatment

The treatment of phantom pain is difficult No one treatment has shown to be effective in a majority of sufferers
Often requires many therapeutic modalities

In a survey of 10,000 amputees, treatment for PLP was successful in 1% (Jin)

PLP- Prevention

Correlation between phantom limb pain and preoperative limb pain Aggressive attempts to control peri-amputation limb pain seems to help
Epidural

Peripheral nerve anesthesia

PLP- Pharmacologic Tx

Anti-seizure / nerve stabilizing medications Tricyclic antidepressants Opiates Anesthetic agents N-methyl-D-aspartate (NMDA) receptor antogonist Ca channel blockers Topical agents such as capsaicin Botox injections Beta-blockers Alpha-2 adrenergic agonists Antiarrhythmics

PLP- Pharmacologic Tx

Gabapentin evidence is mixed

Double Crossover Study 24 patients with RLP or PLP 5-week washout interval Titrated 300 mg - 3,600 mg Measures of pain intensity, pain interference, depression, life satisfaction, and functioning were collected throughout the study. Analyses revealed no significant group differences in pre- to posttreatment scores on any of the outcome measures (Smith)
Double Crossover Study 19 patients 6 weeks UE/LE PLP 1 week washout Gabapentin and placebo both reduced pain vs. baseline but after 6wks, gabapentin was better There was no difference in mood, sleep interference or function with respect to ADLs (Bone)

PLP- Pharmacologic Tx

Evidence for tricyclics is also mixed

Double Blind Controlled Study 39 patients with at least 6 mos PLP 6 wks of amitriptyline (titrated up to 125 mg/d) vs. placebo No difference between drug and placebo Not effective in the treatment of phantom limb pain at the dose used (Robinson)

PLP- Pharmacologic Tx

Botox appears to be effective in some patients

Suggests a peripheral cholinergic effect May be more effective if abnormal activity in stump of PLP patients

Report of 3 phantom and stump pain patients, refractory to previous treatments Total of 500u injected with EMG guidance into points of strong fasciculation Marked improvement in pain intensity & pain medication was reduced significantly in all three cases The duration of response lasted up to 11 weeks (Jin) Case series 4 patients with chronic PLP > 3yrs Injection into 4 areas with 100 IU BTX-A Follow-up 1, 2, 5 wks All reported pain decrease by 60-80% Frequency of pain in 3 down by 90% (Kern)

PLP- Pharmacologic Tx

Opiates are effective, but less so in PLP than in pain of similar intensity of different etiology

Study of 42 cancer patients with limb amputation Monitored monthly first 2 months postoperatively & q 2 months for 2 years. Month 1 versus 2 years after addition of opioid - % with phantom pain decreased from 60% to 32% % of patients with stump pain decreased from 31% to 5% Opioids may help in management of phantom limb pain (Mishra)

PLP- Pharmacologic Tx

Opioids vs. Mexilitene

DBRC crossover trial with 60 patients with 6+ months of PLP 3 treatment arms morphine, mexiletine, placebo 4 wk titration, 2 wk maint, 2 wk taper, 1 wk washout period between treatment arms Pain Decrease: morphine 53%, mexiletine 30%, placebo 19% (significant for morphine vs. placebo) Morphine associated with high incidence side effects and did not improve overall functional activity nor pain-related daily activity (Wu)

PLP- Pharmacologic Tx

Ketamine may help

45 AKA & BKA Pts randomized to receive at anesthesia induction & for 72hrs post-op F/u at 6 months to eval for incidence of PLP Incidence of PLP was 71% in control group, 47% in ketamine group - not statistically significance (p=0.28) (Hayes)

Memantineperhaps

36 Post-traumatic amputees received memantine vs. placebo over 4 wk period 56% UE, 44% LE with > 12 months PLP 2 wks, then tapered off for 1 wk Pain relief in memantine avg =47%; placebo group =40% (not significant) Ten pts in the memantine group (56%) and 6 in the placebo group (33%) had pain relief greater than 50% (Maier)

PLP- Pharmacologic Tx

Memantine 2 case reports

27yo M bilat TF on methadone 10mg TID, gabapentin 1200mg TID, amitriptyline 75mg qHS, celecoxib 200mg BID, dilaudid PCA at 100mg/day Recd memantine 10mg BID x 6 mo. Off opioids on day 1, maintained PLP free on celecoxib only at 8 mo. 21yo M R TT on methadone 5mg TID, dilaudid PCA at 80mg/day, iv fentanyl, nortriptyline 100mg qHS, gabapentin 900mg TID. Recd memantine 10-15mg BID x 4 mo. PLP free and off all meds at 4 mo (Hackworth)

PLP- Pharmacologic Tx

Mirtazepine Calcitonin Pregabalan NSAIDs

CBZ

- effective in one case series - mixed results in literature - No studies showing effective - No controlled trials

- evidence effective against brief stabbing pains, but not other PLP

PLP- Nonpharmacologic Tx

Acupuncture Mirror box

Mostly case studies

60% efficacy

TENS, massage, vibration, contrast baths Nerve blocks

Some evidence for TENS; Gate Theory Mechanism Mixed results

PLP- Nonpharmacologic Tx

ECT

Brain stimulation

One case study showing effectiveness in refractory cases May give temporary & immediate relief, but not as effective in the long term Not as good

Spinal cord stimulation

Dorsal rhizotomy / dorsal column tractectomy / DREZ ablation / thalamotomy

May be effective in refractory cases

PLP- Nonpharmacologic Tx

Deep Brain Stimulation (DBS) seems to help

Deep brain stim of periventricular grey matter & somatosensory thalamus for the relief of chronic PLP in 3 patients Assessed preoperatively and at 3 month intervals postoperatively up to 13 months Periventricular gray stimulation alone was optimal in 2 patients, combination of periventricular gray & thalamic stimulation produced the greatest relief for third patient Intensity of pain was reduced by 62% (range 55-70%) In all three patients, the burning component of the pain was completely alleviated. Morphine intake was reduced in the two patients Quality of life improvement met statistically significance (Bittar)

PLP- Nonpharmacologic Tx

Prosthesis use appears to be effective

Gate theory effect & suggests cortical reorganization also

Case series 21 UE Amputee Constraint-induced movement therapy to reverse cortical-reorganization caused by disuse 9 pts used functional prostheses 12 pts used cosmetic prostheses VAS for pain intensity before and after prosthetic use PLP pain decrease in treatment group was significant (p<0.02) Difference between groups was significant (p<.005) (Weiss)

PLP- Nonpharmacologic Tx

Mirror box

provides a link of visual & motor systems to help recreate a coherent body image & update internal models of motor control may eliminate the remapping associated with phantom limb pains Some evidence that use of mirror reverses these changes, and decreases pain

PLP- Nonpharmacologic Tx

Often a phantom limb is painful because it is felt to be stuck in an uncomfortable or unnatural position, and the patient feels he or she cannot move it
Ramachandran

Small study of 10 patients 5/10 had clenching spasm PLP All 5 had complete relief of PLP while using mirror to unclench the fist Pain was not relieved when not using the mirror (Ramachandran)

PLP- Nonpharmacologic Tx
Virtual reality therapy - Reproduces mirror box in virtual world

8 participants with PLP 2x per week for 8 wks training to follow movements & perform tasks with a virtual image of missing limb Patients reported an average 38% decrease in background pain on a VAS, with 5 patients out of 8 reporting a reduction greater than 30% This decrease in pain was maintained at 4 weeks postintervention in 4 of the 5 participants (Mercier)

PLP- Nonpharmacologic Tx

Virtual reality therapy with motion capture technology

Avatar motion controlled by stump

Case series with 7 UE & 7 LE amputees with PLP Motion capture of stump translated into an avatar in a VR environment Tasks include grab an apple or tap on a bass drum Pain reduction 22-100%, avg 64% Reduction in pain only resulted for pts who experienced agency VR may be useful in alleviating PLP, however effect seems tied to sense of phantom limb agency (Cole)

PLP- Treatment

The treatment of phantom pain is difficult No one treatment has shown to be effective in a majority of sufferers
Often requires many therapeutic modalities

There are many therapeutic options.so try lots of stuff

References:

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References (contd):

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References (contd):

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