Amputee Pain

BC Werner, MD Physical Medicine & Rehabilitation UCSF Department of Orthopaedic Surgery Orthopaedic Trauma Institute San Francisco General Hospital

Outline

Amputee Pain Historical Perspective Current State of Amputee Pain Amputee Pain
Residual Limb Pain Phantom Limb Pain

Treatment Future Considerations

Mount Rushmore

Ambroise Par

(1510-1590) French surgeon to Kings Innovator in battlefield medicine Designed elaborate armor prosthetic limbs Complete Analysis of Post-Amputation Syndrome Differentiated phantom-limb sensation pain-free exteroceptive sensations from phantom-limb pain la douleur s parties amputes Made a clear distinction between phantom (faux sentiments) and residual limb pain

"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"

Proposed neurological models to explain the etiology of phantom-limb pain 1. peripheral changes in stump nerves 2. involved memory, suggesting a cerebral origin of pain

Ren Descartes

(15961650) Philosopher and Mathematician Formulated the modern version of the mindbody paradigm Incongruencies in Objective Experience

God or nature set up these relations for our benefit Our sensations are good guides for most circumstances In certain situations there can be errors in how we sense the world Nerves which reliably tell us when we have hurt our foot, convey the false information to the amputee that he has pain in a foot which is not there. Our senses are not perfect, but within the finite mechanisms of the human mind and body, they are the best we can have

Pain-sensations warn us of bodily damage Pleasure leads us to approach things that (usually) are good for us.

Aaron Lemos

(1774-??) Medical Student at Universitie de Halle 1798 dissertation The Continuing Pain of an Amputated Limb . . . remarks of patients under my care directed my attention to a matter which, in itself, is scarcely new, and yet, it seems to me, still unsatisfactorily explained. Unique theoretical description of processes underlying phantom pain Sensation was carried by the nerves and effected in the brain After an amputation - the power of the nerves to act on the brain is diminished but remains Only his eye and the useless attempts at using the now removed limb convince the patient of his fallacy. The mind faced with this disconnect relies on memory and longstanding associations to reconstruct the lost function Therefore the mind, repeatedly persuaded by sight, will get used to the loss of the limb with the passage of time and will establish a new association series.

Charles Bell

(17741842) Anatomist and Surgeon First to distinguish between sensory and motor nerves First to describe proprioception Considered to be the father of clinical neurology Amputees experience a false sense of the position of a limb and even movements and changes in posture

Silas Weir Mitchell

(1829-1914) Physician and Writer Credited with earliest modern medical description of phantom limb pain Ran Philadelphias Turners Lane Stump Hospital The Case of George Dedlow Introduced to general public
fictional account of quadruple amputee

Herman Melville

Phantom limb pain immortalized 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"

Medical Community

Phantom limb pain was not recognized in Medicine until 1941 Following a study of 50 patients at the Mayo Clinic published by Bailey and Moersch Index Medicus recognized this term in 1954 As of January 2008, over 259 citations in MEDLINE have phantom limb pain as a title word and 893 have this term in any field Besides the limbs, painful phantoms have been described for eyes, nose, teeth, tongue, breast, bladder, and genital organs

Statistics

Over 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

Johannes Mller

(18011856) The belief that these sensations are lost a short time after amputation is an error of medical men, who generally do not watch the patients longer than a few hours

Prevalence of Pain Symptoms

Kooijman 124 UE Schley 96 UE Ephraim 914 Ebde 255 LE Kern 537 Ebrahimzadeh 31 TF Ebrahimzadeh 200 TT Hanley 104 UE Phantom Pain 51% 44.60% 79.90% 72% 74.50% 45.10% 17% 79% Phantom Sensation Residual Limb Pain 76% 49% 53.80% 61.50% NR 67.70% 79% 74% 73.40% 45.20% 87% 64.50% 54% 42% NR 71% Back Pain NR NR 62.30% 52% NR 61.20% 44% 52% Contralateral Pain NR NR NR NR NR 54.80% 38% 33%

2000 2009 2261 PLP 58% (45-79) RLP 59% (42-71) BP 55% (44-62)

Severity

48% experienced pain few times per day or more (Kooijman) 64% experienced moderate to very much suffering from the phantom pain (Kooijman) Nearly all (95%) experienced 1 or more types of amputation-related pain in the previous 4 weeks (Ephraim) Across all pain types, a quarter of those with pain reported their pain to be extremely bothersome (Ephraim) Or to spin it - For most, the pain is episodic and not particularly disabling (Ebde)

Evaluation

Several origins of Amputee Pain Approach from a broad perspective Considers all potential causes Understand pain impact on function Adequate history Thorough physical examination Appropriate Tests Amputation is not a static condition

Resist the initial tendency to consider all pain as being phantom pain

progressive deteriorating condition affecting the health of the amputee over time

Time Frame

Early complications Dehiscence (9.4%) Superficial infection (14.6%) Deep infection (26%) Infection can also present or be detected late . . . Retrospective review 7 TF and 3 TT amputees Residual limb pain and delayed healing prompted radiological, hematological and microbiological investigations Residual Limb Osteomyelitis diagnosed with . . . Average time between amputation and diagnosis of187 days RLO should be considered in any case of delayed wound healing or residual limb pain in amputees (Smith)

Amputee Pain & Depression

Sampled 914 with limb loss Prevalence for significant depressive symptoms was 28.7% Risk factors:
being divorced or separated living at the near-poverty level having comorbid conditions Presence of bothersome back pain Presence of bothersome phantom limb pain Presence of residual limb pain

(Darnall)

Lower levels of phantom limb pain and stump pain associated with positive adjustment to limb loss (Horgan)

Residual Limb Pain

Pain affecting and originating in the residual portion of the limb Prevalence 59% (42-74%)

Etiology of Pain

Residual Limb Pain

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

Trophic Skin Changes Tumor Recurrence

Cellulitis Folliculitis

Neuromas

Develop in all residual limbs after amputation Post-traumatic changes to nerve ends Na Channels Hypersensitive and prone to afferent activity Problematic when entrapped in scar tissue or in position where they are exposed to external mechanical loading Neuropathic Lancinating Pain
Tinels sign Manual palpation Socket pressure Traction of adherent scar tissue

Neuromas

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 nerve end in bone Can reform and become symptomatic

Bone Issues

Arthritis Joints proximal to the site of amputation Use of a prosthesis can place more strain on the proximal joints contributing to arthritis pain Treatment algorithms for non-amputees should be used to maintain function in a prosthesis user (hip replacement) Knee osteoarthritis may be partially relieved by the addition of knee joints and a thigh corset to allow shared weight bearing between the residual limb and the thigh
hips, knees, shoulder

Bone Issues

Terminal Overgrowth Problematic Issue in Skeletally Immature Metaphyseal Level > Diaphyseal Humerus, Fibula, Tibia, and Femur Case Reports of bone overgrowth in Adults (Dudek) Diagnosis Distal Residual Limb Pain Tissue compression Localized Pain and Tenderness Bursa formation Skin ulceration Obtain Radiographs Treatment Socket modification Surgical resection of bone

Bone Issues

Heterotopic Ossification More common in traumatic/combat Blast Injuries Amputations performed in zone of Asymptomatic Painful and Refractory - surgical excision (Potter) Fractures Decreased bone density in Residual Limb Hip and Distal Portion (Sherk) TF osteoporosis and fragility fractures in the hip (Gonzalez) Fall while wearing the prosthesis as the most common cause of injury

Tumor Recurrence

Tumor Recurrence Late pain occurs in a limb amputated because of tumor Local recurrence is a possibility

Dermatologic Disorders

Prevalence 30-50% Hyperhidrosis

More prevalent since advent of silicone liners

Contact Dermatits Infection Cellulitis and Folliculitis

Keratin plugging of sebaceous glands with follicular hyperkeratosis Round or oval swellings deep within the skin Sensitive to touch or pressure The skin may break down and erode or ulcerate
Epidermoid Cysts Dermal Granulomas

Phantom Sensation

Awareness of non-painful sensation in 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

71% (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 Pain

Phantom 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

Prevention

Correlation of phantom limb pain with pre-amputation pain Aggressive attempts to control peri-amputation limb pain Epidural Peripheral nerve anaesthesia

Phantom Pain

Pathophysiology Not completely understood Has this changed in 500 years Several Proposed Theories Peripheral and Spinal Sensitization Somatosensory Cortical Rearrangements Neuromatrix Theory

Phantom Pain

The treatment of phantom pain is difficult No one treatment has shown to be effective in a majority of sufferers.
Can often require many therapeutic modalities

Phantom Pain

Most bothersome to Mitchell was the fact that there was still not an effective way to treat this painful disorder. Additional amputations, nerve resection, cauterization, acupuncture, opiates, morphine, atropine, and other drugs had been tried, but even when changes for the better were observed, they rarely lasted. (Finger)

Treatment

Nerve Stabilizing/Antiseizure Medications gabapentin, carbamazepine Tricyclic Antidepressants amitriptyline, nortriptyline Alpha-2 adrenergic agonists clonidine, tizanidine Local anesthetics mexiletine N-methyl-D-aspartate (NMDA) receptor antogonist Opioids morphine, oxycodone, methadone Nerve blocks Spinal Cord Stimulation/DBS Accupuncture/Magnetic Shielding

Gabapentin

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 change 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)

Tricyclics

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)

Botulinum Toxin

Report of 3 phantom and stump pain patients, refractive to previous treatments All three patients evaluated the clinical global improvement with 3 (marked improvement) The pain intensity and pain medication was reduced significantly in all three cases The duration of response lasted up to 11 weeks (Lin) 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)

Opioids

Study of 42 cancer patients with limb amputation Effectiveness of WHO 3-step analgesic ladder in treating residual limb & phantom limb pain Monitored monthly first 2 months postoperatively and Q2 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% Analgesic ladder / use of opioids may help in management of phantom limb pain (Mishra)

Opioids and Mexiletine

60 patients with 6+ months of PLP 3 treatment arms 4 wk titration, 2 wk maint, 2 wk taper, 1 wk washout period between treatment arms 35 pts completed all 3 arms; mean dose morphine 112mg/day, mexiletine 933 mg/day Pain Decrease: morphine 53%, mexiletine 30%, placebo 19% Morphine associated with high incidence side effects and did not improve overall functional activity and pain-related daily activit (Wu)
morphine, mexiletine, placebo

Ketamine / Memantine: NMDA Antagonist

Ketamine or placebo randomized to receive at anesthesia induction and for 72hrs post-op 45 Patients AKA + BKA pts 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) Memantine vs. placebo over 4 wk period 36; Post-traumatic amputees, 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% Ten pts in the memantine group (56%) and 6 in the placebo group (33%) had pain relief greater than 50% (Maier)

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)

Central Stimulation

3 patients Deep Brain Stimulation of periventricular grey matter and somatosensory thalamus for the relief of chronic neuropathic pain associated with phantom limb in three patients Assessed preoperatively and at 3 month intervals postoperatively up to 13 months Periventricular gray stimulation alone was optimal in two patients, combination of periventricular gray and thalamic stimulation produced the greatest degree 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 sulphate intake was reduced in the two patients Quality of life measures indicated a statistically significant improvement (Bittar)

Cortical Re-Organizaion

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) Phantom limb pain and cortical re-organization are positively related (Flor) Telescoping phantoms with increased pain lead to greater cortical reorganization (Karl)

Cortical Re-Organization

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 Ramachadran Small study 10 patients n=10 6/10 had agency, 4/10 no agency (excluded) 5/10 (all with agency) 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 (Ramachadran)

Some evidence that use of mirror reverses these changes, and decreases pain (Flor).
Use mirror box may eliminate the remapping associated with phantom limb pains.

Virtual Reality Therapy

Case series 7 upper and 7 lower limb 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 and identified with the virtual limb VR may be useful in alleviating PLP, however effect seems tied to sense of phantom limb agency (Cole)

Virtual Reality Therapy

8 Male participants with phantom limb pain (PLP) Several times per week times per week for 8 followed movements of virtual image of a missing limb Patients reported an average 38% decrease in background pain on a visual analog scale (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)

Cortical Re-Organization

Aware of the lack of a once associated organ, the mind tried to supply its functions. But since the mind had become accustomed to association, it strove immediately to restore the original association . . . And therefore the mind, repeatedly persuaded by sight, will get used to the loss of the limb with the passage of time and will establish a new association series. It is only after a long time that this fallacious sensation is utterly extinguished, because the mind cannot immediately remove previously acquired associations and needs time to get used to these new representations. Aaron Lemos 1798

Prosthesis Use

Case series 21 UE Amputee Constraint-induced movement therapy ala post-CVA to reverses cortical-reorganization caused by disuse 9 pts used Sauerbruch prosthesis 12 pts used a cosmetic prosthesis VAS for pain intensity before and after prosthetic use. PLP pain decrease in treatment group was signif (p<0.02) Difference between groups was signif (p<.005) (Weiss)

Cortical Re-Organization
Captain Ahab: Look ye, carpenter, I dare say thou callest thyself a right good workmanlike workman, eh? Well, then, will it speak thoroughly well for thy work, if, when I come to mount this leg thou makest, I shall nevertheless feel another leg in the same identical place with it; that is, carpenter, my old lost leg; the flesh and blood one, I mean. Canst thou not drive that old Adam away?

Thank You

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