Abstract
There is increasing evidence that nerve growth factor (NGF) plays a role in the prolonged pain associated with inflammation and thus promotes the development of chronic pain. An increase in the tissue level of NGF occurs within hours of the initiation of inflammation. NGF produces prolonged thermal and mechanical hyperalgesia. The thermal hyperalgesia results in part from sensitization of nociceptors, while mechanical hyperalgesia involves central changes. NGF locally produced by inflammation is retrogradely transported to the dorsal root ganglion (DRG) and triggers the upregulation of vaniloid receptor-1, tetrodotoxin-resistant Na+ channels, brain-derived neurotrophic factor (BDNF), calcitonin gene-relatedpeptide (CGRP) and substance P within the cell bodies of nociceptive primary sensory neurons in DRG. BDNF is transported to central terminals in dense core vesicles and released from central terminals. BDNF in turn phosphorylates NMDA receptors, and mediates the hyperexcitability of secondary nociceptive neurons within the spinal cord.
Pain of postherpetic neuralgia (PHN) is often of 3 types; ongoing pain, superimposed paroxysmal pain and allodynia. There are sensory deficits affecting all modalities in the involved dermatomes, indicative of partial deafferentation. Topically applied lidocaine relieves pain in some PHN patients. It is likely that ectopic impulses are generated from surviving axons and induce hypersensitivity of secondary nociceptive neurons in such cases. Allodynia is most often elicited by innocuous moving, and the mechanical allodynia appears to be mediated by large tactile fibers. This implies abnormal synaptic connectivity at the spinal cord level between large afferent fibers and central pain signalling secondary neurons. The windup response of wide dynamic range (WDR) neurons which normally occurs in response to repetitive C fiber stimulation through activation of NMDA receptors, may be brought about by large tactile fiber inputs in PHN. This may account for the windup of tactile allodynia in PHN.
