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

doi:10.1016/S0304-3940(98)00738-1

Neuroscience Letters

Volume 256, Issue 1, 30 October 1998, Pages 17-20

https://doi.org/10.1016/S0304-3940(98)00738-1 Get rights and content

Abstract

We report evidence for a contribution of tetrodotoxin-resistant sodium current (TTX-R I_Na) 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 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 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 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.

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Acknowledgements

Supported by NIH grant NS21647 and the Giannini foundation.

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

Abstract

Section snippets

Acknowledgements

Neuroscience

Neuroscience

Neurosci. Lett.

Neurosci. Lett.

Neuroscience

Neuroscience

Neuroscience

J. Biol. Chem.

Brain Res.