title: Calcium channels as therapeutic targets in neuropathic pain.
abstract: Injury to the nerve can produce changes in dorsal horn function and pain. This facilitated processing may be mediated in part by voltage-sensitive calcium channels. Activation of these channels increases intracellular calcium, thereby mediating transmitter release and activating cascades serving to alter membrane excitability and initiate protein transcription. Molecular techniques reveal the complexity and multiplicity of these channels. At the spinal level, blocking of several of these calcium channels, notably those of the N type, can prominently alter pain behavior. These effects are consistent with the high levels of expression on primary afferents and dorsal horn neurons of these channels. More recently, agents binding to auxiliary subunits such as the alpha2delta of these calcium channels diminish excitability of the membrane without completely blocking channel function. Drugs that bind to this site, highly expressed in the superficial dorsal horn, will diminish neuropathic pain states. Continuing developments in our understanding of these channel functions promises to advance the control of aberrant spinal functions initiated by nerve injury.
  
  
  CONCLUSIONS
  Pharmacologic studies showing the role of spinal voltage-sensitive calcium channels in neuropathic pain models provide evidence suggesting their applicability in human pain states.
authors.affiliation: Department of Anesthesiology, University of California, San Diego, La Jolla, California 92093-0818, USA. tyaksh@ucsd.edu
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yaksh
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000503:physiopathology
chemical_list: D000700:Analgesics; D002121:Calcium Channel Blockers; D015220:Calcium Channels