title: Voltage-gated sodium channels and pain pathways.
abstract: Acute, inflammatory, and neuropathic pain can all be attenuated or abolished by local treatment with sodium channel blockers such as lidocaine. The peripheral input that drives pain perception thus depends on the presence of functional voltage-gated sodium channels. Remarkably, two voltage-gated sodium channel genes (Nav1.8 and Nav1.9) are expressed selectively in damage-sensing peripheral neurons, while a third channel (Nav1.7) is found predominantly in sensory and sympathetic neurons. An embryonic channel (Nav1.3) is also upregulated in damaged peripheral nerves and associated with increased electrical excitability in neuropathic pain states. A combination of antisense and knock-out studies support a specialized role for these sodium channels in pain pathways, and pharmacological studies with conotoxins suggest that isotype-specific antagonists should be feasible. Taken together, these data suggest that isotype-specific sodium channel blockers could be useful analgesics.
authors.affiliation: Molecular Nociception Group, Department of Biology, University College, Gower Street, London WC1E 6BT, UK. J.Wood@ucl.ac.uk
authors.forename: John N
authors.initials: JN
authors.lastname: Wood
authors.forename: James P
authors.initials: JP
authors.lastname: Boorman
authors.forename: Kenji
authors.initials: K
authors.lastname: Okuse
authors.forename: Mark D
authors.initials: MD
authors.lastname: Baker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010146:Pain / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D009479:Neuropeptides; D026941:Sodium Channel Blockers; D015222:Sodium Channels