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

Neurosci Lett. 1998 Oct 30;256(1):17-20. doi: 10.1016/s0304-3940(98)00738-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antisense Elements (Genetics) / genetics
  • Dinoprostone
  • Drug Resistance
  • Electric Conductivity
  • Hindlimb / physiopathology
  • Hyperalgesia / chemically induced
  • Hyperalgesia / physiopathology
  • Inflammation / physiopathology*
  • Male
  • Nociceptors / physiology
  • Pain / physiopathology*
  • Pain Measurement
  • Rats
  • Rats, Sprague-Dawley
  • Reflex / physiology
  • Sodium Channels / genetics
  • Sodium Channels / physiology*
  • Tetrodotoxin / pharmacology*


  • Antisense Elements (Genetics)
  • Sodium Channels
  • Tetrodotoxin
  • Dinoprostone