title: The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity.
abstract: We used a mouse with deletion of exons 4, 5, and 6 of the SCN11A (sodium channel, voltage-gated, type XI, alpha) gene that encodes the voltage-gated sodium channel Na(v)1.9 to assess its contribution to pain. Na(v)1.9 is present in nociceptor sensory neurons that express TRPV1, bradykinin B2, and purinergic P2X3 receptors. In Na(v)1.9-/- mice, the non-inactivating persistent tetrodotoxin-resistant sodium TTXr-Per current is absent, whereas TTXr-Slow is unchanged. TTXs currents are unaffected by the mutation of Na(v)1.9. Pain hypersensitivity elicited by intraplantar administration of prostaglandin E2, bradykinin, interleukin-1beta, capsaicin, and P2X3 and P2Y receptor agonists, but not NGF, is either reduced or absent in Na(v)1.9-/- mice, whereas basal thermal and mechanical pain sensitivity is unchanged. Thermal, but not mechanical, hypersensitivity produced by peripheral inflammation (intraplanatar complete Freund's adjuvant) is substantially diminished in the null allele mutant mice, whereas hypersensitivity in two neuropathic pain models is unchanged in the Na(v)1.9-/- mice. Na(v)1.9 is, we conclude, an effector of the hypersensitivity produced by multiple inflammatory mediators on nociceptor peripheral terminals and therefore plays a key role in mediating peripheral sensitization.
authors.affiliation: Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Fumimasa
authors.initials: F
authors.lastname: Amaya
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Costigan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Allchorne
authors.forename: Jon P
authors.initials: JP
authors.lastname: Hatcher
authors.forename: Julie
authors.initials: J
authors.lastname: Egerton
authors.forename: Tania
authors.initials: T
authors.lastname: Stean
authors.forename: Valerie
authors.initials: V
authors.lastname: Morisset
authors.forename: David
authors.initials: D
authors.lastname: Grose
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Gunthorpe
authors.forename: Iain P
authors.initials: IP
authors.lastname: Chessell
authors.forename: Simon
authors.initials: S
authors.lastname: Tate
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Green
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
mesh_terms: D000818:Animals; D005260:Female; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009475:Neurons, Afferent / Q000378:metabolism; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D010146:Pain / Q000235:genetics / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D010525:Peripheral Nerves / Q000378:metabolism*; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C491885:Scn11a protein, mouse; D015222:Sodium Channels