Pathophysiological and Neuroplastic Changes in Postamputation and Neuropathic Pain: Review of the Literature

Abstract

Background: Despite advancements in surgical and rehabilitation strategies, extremity amputations are frequently associated with disability, phantom limb sensations, and chronic pain. Investigation into potential treatment modalities has focused on the pathophysiological changes in both the peripheral and central nervous systems to better understand the underlying mechanism in the development of chronic pain in persons with amputations. Methods: Presented in this article is a discussion outlining the physiological changes that occur in the peripheral and central nervous systems following amputation. In this review, the authors examine the molecular and neuroplastic changes occurring in the nervous system, as well as the state-of-the-art treatment to help reduce the development of postamputation pain. Results: This review summarizes the current literature regarding neurological changes following amputation. Development of both central sensitization and neuronal remodeling in the spinal cord and cerebral cortex allows for the development of neuropathic and phantom limb pain postamputation. Recently developed treatments targeting these pathophysiological changes have enabled a reduction in the severity of pain; however, complete resolution remains elusive. Conclusions: Changes in the peripheral and central nervous systems following amputation should not be viewed as separate pathologies, but rather two interdependent mechanisms that underlie the development of pathological pain. A better understanding of the physiological changes following amputation will allow for improvements in therapeutic treatments to minimize pathological pain caused by amputation.

Attenuation of acute postoperative pain and opioid requirement with the use of magnesium sulfate in patients undergoing limb amputations

“…Pain following limb amputations is thought to be mediated by the NMDA receptor, which is one of the primary excitatory neurotransmitters that carry pain signals from the dorsal horn to the brain. 21,22 The activation of this receptor causes neuronal sensitisation, leading to hyperalgesia, neuropathic pain and reduced opioid R.S. Qureshi, T. Alam, A.W.…”

Silencing the Phantom - Pregabalin Misuse in Amputation Patients: A Case Report

“…Doing so blocks calcium influx, limiting the neuron's ability to release glutamate and P into the synapse. Furthermore, studies have suggested that pregabalin may help reduce spontaneous nerve firing in damaged nerve fibers within the stump and adjacent fibers in patients with PLSynd (35).…”

Chronic pain and local pain in usually painless conditions including neuroma may be due to compressive proximal neural lesion

“…Increased excitability of sensory neurons is due to reduction of activation threshold of their ion channels, which may be caused by nerve injury, inflammation (arising from both neural and non-neural tissue), and by ion channel mutations ( 68 , 78 , 79 ). Although there are many mechanisms involved in sensitization, abnormal peripheral neuronal activity plays a key role as a triggering input ( 25 , 26 , 80 ). In this regard, nociceptive sensitization can electrophysiologically be understood as ongoing (spontaneous) activity and mechanical sensitivity of primary sensory fibers ( 81 ), which relates to neuronal hyperexcitability.…”