A tetrodotoxin-resistant sodium current mediates inflammatory pain in the rat

We report evidence for a contribution of tetrodotoxin-resistant sodium current (TTX-R I-Na) to prostaglandin E-2 (PGE(2))-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 I-Na (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 PGE(2)-induced hyperalgesia. PGE(2)-induced hyperalgesia returned to normal 7 days after the last injection of antisense ODN. Antisense ODN selectively and significantly reduced TTX-R I-Na current density in cultured sensory neurons. Our observations support the hypothesis that modulation of TTX-R I-Na, present in peripheral terminals of primary afferent nociceptors, contributes, at least in part, to inflammatory hyperalgesia. Since TTX-R I-Na is found only in primary afferent nociceptors, our findings suggest TTX-R I-Na as a promising target for novel therapeutic interventions for the treatment of inflammatory pain. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.