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

NEUROSCIENCE LETTERS

卷:256

Article

Khasar, SG ; Gold, MS ; Levine, JD

关键词: tetrodotoxin-resistant sodium current;    pain;    hyperalgesia;    primary afferent nociceptor;    sensitization;   

DOI  :  10.1016/S0304-3940(98)00738-1

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free