Morning Report Steven Hart

HPI 45 year old female presents to clinic to establish new PMD CC: left leg pain Recent medical history Pain in left LE for 1 mo with several visits to ER left femoral thrombus and emboli to left lower extremity eventually diagnosed Left AKA required Now (6 weeks later) c/o persistent pain where lower left leg was and sensations in left leg. Started on coumadin prior to discharge

Physical exam C/w left AKA Exam otherwise unremarkable Incisions clean and healing well Non-tender, no erythema, skin intact Exam otherwise unremarkable

Topics Phantom Limb Pain (PLP) Definitions Epidemiology Etiology / Pathophysiology Evaluation / Differential Treatment Prevention / Short term Long term

Definitions Stump pain Phantom Limb Pain (PLP) Pain in the residual portion of the limb Phantom Limb Pain (PLP) A painful sensation perceived in a missing limb after amputation Phantom Limb Sensation (PLS) Any sensation of the missing limb (paresthesia, dysesthesia, hyperpathia) except pain.

Epidemiology Phantom Limb Sensation (PLS) Occurs in 85% - 98% of amputees within 3 weeks of amputation 8% may occur after 1-12 months Usually resolves after 2 – 3 years spontaneously if PLP does not develop Location affects intensity and likelihood of PLS Proximal ie. Above the knees or elbows Dominant extremity

Epidemiology Phantom Limb Pain (PLP) 60-70% of amputes experience PLP Location again an important factor Proximal 68-88% hemipelvectomy 40-88% hip disarticulation 51% upper limb 20% AKA 0-2% BKA

Epidemiology Phantom Limb Pain (PLP) – continued Time Occurs 1 week to decades after amputation Pain onset after one year in < 10% May diminish and eventually resolve with time More likely, however, it will persist chronically Pain in limb prior to amputation increases risk for PLP Pains in other parts of the body Headache Joint pain Sore throat Abd pain Back pain

Epidemiology Stump Pain Occurs in about 50% of amputees Frequently associated with phantom pain

Etiology Neuromas Dominate theory until last 10-15 years Irritation of the severed nerve endings Inflammation resulted in anomalous signals to the brain perceived as pain. Treatments included removal of nerve endings or further amputation. Only resulted in temporary improvement Eventually pain returned, frequently worse Modern thought - One of many factors causing PLP

Etiology Neuroma – their role  mechanical/neurostimulation  spontaneous and abnormal evoked activity   in sodium channel production   in sensitivity of neuromas to norepinephrine Thus, pain with stress or other emotional states A similar phenomenon occurs in the cell body of the dorsal root ganglia just upstream

Etiology -spinal cord level  signal from neuromas and doral root ganglia cell bodies   activity of neurons in dorsal horns   upregulation of several genes - especially receptive genes -  in N-methyl-D-aspartate (NDMA)

Etiology -spinal cord level Anatomical reorganization (rewiring) Perph nerve transection  degeneration of afferent C-fiber terminals in Lamina II These may replaced by A mechanoreceptive afferents Results in pain evoked by simple touch

Etiology - Central mechanism Somatosensory cortex remapping PLS/PLP evoked by touching face in a hand amputee Verified by multiple neuroimaging studies in humans

Etiology - Central mechanism Plastic changes occur in the Thalamus Stimulation of thalamus in amputees causes PLP and PLS Similar stimulation does not cause any pain in non-amputees

Differential Diagnosis of PLP Radicular pain Disk herniation Angina Post herpetic neuralgia Metastatic cancer Infection / poor wound healing

Treatment of PLP -Overview Poorly studied field placebo effect common Spontaneous resolution does happen Fewer than 10% of PLP patients receive lasting relief Frequently, neuropathic treatment recommended, but few studies to support this Most neuropathic treatment trials do not include PLP Prevention of PLP is a new area of interest

Treatment of PLP -Overview Multiple approaches Prevention Medical Physical Therapy Nerve Blocks Nerve stimulation Transcutaneous, spinal cord, deep brain, motor ECT Psychological Therapy

Treatment of PLP -Prevention Goal – avoid/control the changes that lead to chronic pain Prevent or control pre, peri and post-operative pain Use of pre, intra and post-op epidural blocks has been shown to reduce occurrence of PLP at 12 mo post-op Mixed results in follow up studies

Treatment of PLP -Prevention Calcitonin infusions Ketamine Transcutaneous electrical stimulation

Treatment of PLP -Medical Management Anti-depressants Tricyclic anti-depressants Anti-convulsants NMDA receptor antagonists Opiates Beta Blockers Misc

Treatment of PLP -Medical Management Tricyclic anti-depressants Frequently used Well studied in other neuropathic pain syndromes Diabetes, post herpetic neuralgia Poorly studied in PLP One randomized study showed no effect, other studies showed some benefit

Treatment of PLP -Medical Management Anti-convulsants Carbamazepine Effective for intense, brief, lancinating type of pain Gabapentin Effective in one small randomized trial Topiramate Small randomized study supported it effectiveness

Treatment of PLP -Medical Management Opiates Effective for both stump pain and PLP May affect cortical reorganization Considered the mainstay of treatment Tolerance/Addiction Most amputees have a short life expectancy because of underlying disease. Balance quality of life vs risk of opiate addiction/dependence

Treatment of PLP -Medical Management NMDA receptor antagonists Ketamine – effective, must be IV Memantine – oral, ineffective Dextromethorphan Small randomized studies have supported its use. Improved feeling No, small sedation No increased side effects from placebo

Treatment of PLP -Physical Therapy Sensory discrimination training Designed to alter the cortical map Shown to significantly reduce PLP and cortical reorganization

Treatment of PLP -Neurostimulation Transcutaneous electrical nerve stimulation Spinal Cord Stimulation Deep brain stimulation Motor cortex stimulation All very preliminary

Treatment of PLP Acupuncture ECT Psychological Therapy May provide short term relief ECT Several case reports of pain resolution after treatment Psychological Therapy Relaxation training hypnosis

Conclusion PLP is common in amputees The cause is complicated and involves virtually all levels of the nervous system Prevention of chronic pain may be possible but further investigation is needed Chronic pain management is difficult and should be multifaceted There is little evidence to guide therapy at this time.