Basic mechanisms underlying persistent pain after nerve injury

Abstract

Animal models of nerve injury‐induced neuropathic pain have identified peripheral and CNS factors that initiate and maintain the condition. Among the major peripheral contributors are ectopic firing of injured afferents and abnormal interplay of sympathetic efferents and primary afferent nociceptors (‘pain fibers’). Peripheral nerve injury also triggers changes at the level of the dorsal horn, including loss of large fiber inhibition, loss of GABAergic interneurons, induction of microglia that are the source of pronociceptive molecules, as well as the loss of descending brainstem inhibitory controls and the release of descending facilitatory mechanisms. These changes sensitize spinal cord and brain pain transmission circuits, such that there is ongoing spontaneous activity as well as activation of pain transmission circuits by normally innocuous stimuli, leading to the condition of allodynia, in which pain is produced by non‐painful stimuli. The general consensus is that neuropathic pain responds rarely to non‐steroidal anti‐inflammatory drugs and is poorly managed by opiates. Alternative treatment approaches, including local anesthetics, anticonvulsants and anti‐depressants will be discussed.