title: A tetrodotoxin-resistant sodium current mediates inflammatory pain in the rat.
abstract: We report evidence for a contribution of tetrodotoxin-resistant sodium current (TTX-R INa) to prostaglandin E2 (PGE2)-induced hyperalgesia. Behavioral experiments were performed in rats chronically implanted with spinal cannulae. The study employed intrathecal administration of oligodeoxynucleotide (ODN) antisense to the recently cloned channel underlying TTX-R INa (PN3/SNS). The nociceptive flexion reflex was employed to determine changes in mechanical stimulus-induced paw-withdrawal threshold. Administration of antisense but not of sense or mismatch ODN, led to a decrease in PGE2-induced hyperalgesia. PGE2-induced hyperalgesia returned to normal 7 days after the last injection of antisense ODN. Antisense ODN selectively and significantly reduced TTX-R INa current density in cultured sensory neurons. Our observations support the hypothesis that modulation of TTX-R INa, present in peripheral terminals of primary afferent nociceptors, contributes, at least in part, to inflammatory hyperalgesia. Since TTX-R INa is found only in primary afferent nociceptors, our findings suggest TTX-R INa as a promising target for novel therapeutic interventions for the treatment of inflammatory pain.
authors.affiliation: Department of Anatomy, Medicine and Oral Maxillofacial Surgery, Graduate Program in Neuroscience, NIH Pain Center (UCSF), University of California, San Francisco 94143-0440, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Khasar
authors.forename: M S
authors.initials: MS
authors.lastname: Gold
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics; D015232:Dinoprostone; D004351:Drug Resistance; D004553:Electric Conductivity; D006614:Hindlimb / Q000503:physiopathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: D016375:Antisense Elements (Genetics); D015222:Sodium Channels; D013779:Tetrodotoxin; D015232:Dinoprostone