title: Pathways that elicit long-term changes in gene expression in nociceptive neurons following nerve injury: contributions to neuropathic pain.
abstract: Chronic neuropathic pain following nerve injury or inflammation is mediated by transcription-dependent changes in neurons that comprise the nociceptive pathway. Among these changes is often a long-term hyperexcitability (LTH) in primary nociceptors that persists long after the lesion has healed. LTH is manifest by a reduction in threshold and an increased tendency to fire action potentials. This increased excitability activates higher order neurons in the pathway, leading to the perception of pain. Efforts to ameliorate chronic pain would therefore benefit if we understood how LTH is induced, but studies toward this goal are impeded by the complexity and heterogeneity of vertebrate nervous systems. Fortunately, LTH is an evolutionarily conserved mechanism that underlies defensive behaviors across phyla, including invertebrates. Thus, the same electrophysiological changes that underlie LTH in vertebrate nociceptive neurons are seen in their counterparts in the experimentally favorable mollusk Aplysia californica. Nociceptive neurons of Aplysia are readily accessible and large enough to approach using a variety of cell and molecular approaches not possible in higher organisms. Studies of the molecular cascades activated by injury to Aplysia peripheral nerves has focused on a group of positive injury signals that are retrogradely transported from the injury site in the axon to the cell nucleus where they regulate gene transcription. One of these, protein kinase G, is activated by nitric oxide synthetase and its activation in axons is required for the induction of LTH after injury. This pathway, and the transcriptional events that it activates, are targets for therapeutic intervention for chronic pain.
authors.affiliation: Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Sung
authors.forename: Richard T
authors.initials: RT
authors.lastname: Ambron
mesh_terms: D000818:Animals; D002908:Chronic Disease; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000235:genetics / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013995:Time