Mechanisms of neuropathic pain

Abstract 

Neuropathic pain is a disease of global burden. Its symptoms include spontaneous and stimulus-evoked painful sensations. Several maladaptive mechanisms underlying these symptoms have been elucidated in recent years: peripheral sensitization of nociception, abnormal excitability of afferent neurons, central sensitization comprising pronociceptive facilitation, disinhibition of nociception and central reorganization processes, and sympathetically maintained pain. This review aims to illustrate these pathophysiological principles, focussing on molecular and neurophysiological findings. Finally therapeutic options based on these findings are discussed.

Abbreviations: AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazeloproprionic acid, ASIC, acid sensing ion channel, CGRP, calcitonin gene-related peptide, CIP, congenital insensitivity to pain, CRPS, complex regional pain syndrome, DRG, dorsal root ganglion, HPC-nociceptors, nociceptors sensitive to heat, pinch and cold, LPA, lysophosphatidic acid, LTP, long-term potentiation, MAPK, mitogen-activated protein kinase, mGluR, metabotropic G-protein coupled glutamate receptor, Na_V, voltage-gated sodium channel, NGF, nerve growth factor, NMDA, N-methyl-D-aspartate, PAG, periaqueductal grey, PEPD, paroxysmal extreme pain disorder, QST, quantitative sensory testing, RVM, rostral ventral medulla, SCS, spinal cord stimulation, SSRI, selective serotonin reuptake inhibitor, TCA, tricyclic antidepressant, TENS, transcutaneous electrical nerve stimulation, TRP, transient receptor potential-channel, TTX, tetrodotoxin

Keywords: Neuropathic pain, Pathophysiology, Sensitization, Reorganization, Sympathetically maintained, Symptoms