Phantom Limb Pain: Mechanisms and Treatment Approaches

Abstract

The vast amount of research over the past decades has significantly added to our knowledge of phantom limb pain. Multiple factors including site of amputation or presence of preamputation pain have been found to have a positive correlation with the development of phantom limb pain. The paradigms of proposed mechanisms have shifted over the past years from the psychogenic theory to peripheral and central neural changes involving cortical reorganization. More recently, the role of mirror neurons in the brain has been proposed in the generation of phantom pain. A wide variety of treatment approaches have been employed, but mechanism-based specific treatment guidelines are yet to evolve. Phantom limb pain is considered a neuropathic pain, and most treatment recommendations are based on recommendations for neuropathic pain syndromes. Mirror therapy, a relatively recently proposed therapy for phantom limb pain, has mixed results in randomized controlled trials. Most successful treatment outcomes include multidisciplinary measures. This paper attempts to review and summarize recent research relative to the proposed mechanisms of and treatments for phantom limb pain.

Percutaneous image-guided cryoablation for the treatment of phantom limb pain in amputees: a pilot study

“…PLP-pain perceived to originate from an absent body part after amputation-represents the symptomatic end manifestation of ectopic inputs along this transformed pathway (19)(20)(21). Numerous studies have reported on interventions at different points along this altered pathway, from direct and indirect cortical modulation to surgical resection of the distal residual nerve (and at many points in between), yet no accepted guidelines for treatment have emerged (21)(22)(23)(24)(25)(26).…”

“…PLP-pain perceived to originate from an absent body part after amputation-represents the symptomatic end manifestation of ectopic inputs along this transformed pathway (19)(20)(21). Numerous studies have reported on interventions at different points along this altered pathway, from direct and indirect cortical modulation to surgical resection of the distal residual nerve (and at many points in between), yet no accepted guidelines for treatment have emerged (21)(22)(23)(24)(25)(26). Treatment strategies targeting the peripheral nerve, such as catheter placement for infusion of anesthetic postoperatively, peripheral neuromodulation, lidocaine injections, and cryoanalgesia guided by nerve stimulation, have been reported more recently as potentially efficacious (27)(28)(29)(30).…”

“…Plasticity and "windup" related to peripheral nerve scar tissue traction, compression of residual nerves, ischemia, or peripheral upregulation of ectopic ion channels contributes to unpleasant sensations that localize to the deafferented body part (31). The microenvironment around a peripheral axotomy induces biochemical changes that result in increased expression of voltage-sensitive sodium channels, decreased potassium channel expression, altered transduction molecules involved in mechanosensitivity and heat and cold sensitivity, increased concentrations of inflammatory mediators, and altered adrenoreceptor subtype expression-the end product of which are ectopic action potentials (21,29,(32)(33)(34). These "firings" have been characterized and implicated in the establishment of ongoing noxious signals, intensification, and summation effects on ectopic signals from the dorsal root ganglion, central nervous system reorganization, and global neuraxis sensitization, not to mention the pain itself (19,20,25,35).…”

Phantom Limb Pain: What do we know so far?

“…In most recent years however it is thought that cortical reorganization plays an important role in pain transmission. It is believed that cortical areas representing the amputated extremity are taken over by surrounding association areas in both the primary somatosensory and motor cortex [7,8].…”

“…Common and important medical treatment methods include the use of TCAs, anticonvulsants, lidocaine (as a sympatholytic), opiods, NMDA receptor anatagonists (to counter-act neural plasticity) and benzodiazepines to name a few. Surgical treatment more or less has now been forgotten and abandoned due to unfavorable results in the general population [8]. Non pharmacological methods have found some interesting results, however these are limited by the low quality of evidence of the studies [9].…”