Neuronal plasticity and signal transduction in nociceptive neurons: Implications for the initiation and maintenance of pathological pain

Pathological pain, consisting of tissue injury-induced inflammatory and ner ve injury-induced neuropathic pain, is an expression of neuronal plasticity . One component of this is that the afferent input generated by injury and intense noxious stimuli triggers an increased excitability of nociceptive n eurons in the spinal cord. This central sensitization is an activity-depend ent functional plasticity that results from activation of different intrace llular kinase cascades leading to the phosphorylation of key membrane recep tors and channels, increasing synaptic efficacy. Central sensitization is b oth induced and maintained in a transcription-independent manner. Several d ifferent intracellular signal transduction cascades converge on MAPK (mitog en-activated protein kinase), activation of which appears to be a master sw itch or gate for the regulation of central sensitization. In addition to po sttranslational regulation, the MAPK pathway may also regulate long-term pa in hypersensitivity, via transcriptional regulation of key gene products. P harmacological intervention targeted specifically at the signal transductio n pathways in nociceptive neurons may provide, therefore, new therapeutic o pportunities for pathological pain. (C) 2001 Academic Press.