Postamputation pain: epidemiology, mechanisms, and treatment

Abstract

Postamputation pain (PAP) is highly prevalent after limb amputation but remains an extremely challenging pain condition to treat. A large part of its intractability stems from the myriad pathophysiological mechanisms. A state-of-art understanding of the pathophysiologic basis underlying postamputation phenomena can be broadly categorized in terms of supraspinal, spinal, and peripheral mechanisms. Supraspinal mechanisms involve somatosensory cortical reorganization of the area representing the deafferentated limb and are predominant in phantom limb pain and phantom sensations. Spinal reorganization in the dorsal horn occurs after deafferentataion from a peripheral nerve injury. Peripherally, axonal nerve damage initiates inflammation, regenerative sprouting, and increased “ectopic” afferent input which is thought by many to be the predominant mechanism involved in residual limb pain or neuroma pain, but may also contribute to phantom phenomena. To optimize treatment outcomes, therapy should be individually tailored and mechanism based. Treatment modalities include injection therapy, pharmacotherapy, complementary and alternative therapy, surgical therapy, and interventions aimed at prevention. Unfortunately, there is a lack of high quality clinical trials to support most of these treatments. Most of the randomized controlled trials in PAP have evaluated medications, with a trend for short-term Efficacy noted for ketamine and opioids. Evidence for peripheral injection therapy with botulinum toxin and pulsed radiofrequency for residual limb pain is limited to very small trials and case series. Mirror therapy is a safe and cost-effective alternative treatment modality for PAP. Neuromodulation using implanted motor cortex stimulation has shown a trend toward effectiveness for refractory phantom limb pain, though the evidence is largely anecdotal. Studies that aim to prevent PA P using epidural and perineural catheters have yielded inconsistent results, though there may be some benefit for epidural prevention when the infusions are started more than 24 hours preoperatively and compared with nonoptimized alternatives. Further investigation into the mechanisms responsible for and the factors associated with the development of PAP is needed to provide an evidence-based foundation to guide current and future treatment approaches.

Preoperative use of pregabalin for acute pain in spine surgery

“…Choi et al [14] reported that the occurrence of chronic pain after spine surgery was approximately 20%, and this incidence is lower than the 32% following discectomy and up to 85% observed after amputation. [25–27] If the theory proposed by Eipe et al [24] is correct, then the lower incidence of chronic pain after spine surgery may explain why pregabalin failed to demonstrate efficacy in patients undergoing spine surgery.…”

Regenerative Peripheral Nerve Interfaces for the Treatment of Postamputation Neuroma Pain: A Pilot Study

“…7 The neuroma’s afferent fibers develop ectopic activity, mechanical sensitivity, and chemosensitivity to catecholamines. 8 The altered expression of transduction molecules, upregulation of sodium channels, downregulation of potassium channels, and development of nonfunctional connections between axons all contribute to the hyperexcitability and spontaneous discharge witnessed within injured nerves. 9 Nonsurgical treatment includes desensitization, chemical or anesthetic injections, transcutaneous electrical nerve stimulation, topical lidocaine, and adjuvant pain medications such as antidepressants and anticonvulsants.…”

“…7 Fibrin patch application with placement of a local pain catheter has also been described. 16 The long-term outcomes of such methods are mixed, 6,8 likely because of the nonphysiological nature of these treatments.…”

Clinical Trial of the Virtual Integration Environment to Treat Phantom Limb Pain With Upper Extremity Amputation

“…Following limb loss, almost everyone experiences phantom limb sensations, which include the perception of itching, pressure, or temperature changes in the phantom limb, as well as an awareness of its orientation in space (2). Furthermore, reports estimate that 85% of all persons with amputation experience painful sensations, or phantom limb pain (PLP), either immediately following amputation or within days to weeks post-operation (3). For many, both phantom sensations and PLP are bothersome and even disabling, interfering with the ability to live independently and further emphasizing the need for successful treatment interventions.…”