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DAMGO inhibits prostaglandin E2-induced potentiation of a TTX-resistant Na+ current in rat sensory neurons in vitro

1996; Elsevier BV; Volume: 212; Issue: 2 Linguagem: Inglês

10.1016/0304-3940(96)12791-9

1872-7972

Michael S. Gold, Jon D. Levine,

Neuropeptides and Animal Physiology

We have tested the hypothesis that the μ-opioid agonist, [d-Ala2,N-Me-Phe4,Gly5-ollenkephalin (DAMGO), inhibits prostaglandin E2 (PGE2)-induced modulation of a tetrodotoxin-resistant voltage-gated Na+ current (TTX-R INa) in putative nociceptors in vitro. Patch-clamp electrophysiological techniques were used on cultured dorsal root ganglion neurons from the adult rat. PGE2 (1 μM) induced a 103 ± 22.8% increase in peak TTX-R INa. The PGE2-induced increase in TTX-R INa in the presence of l μM DAMGO (24.9 ± 7.7%), was significantly less than that induced by PGE2 alone. In contrast, when DAMGO was applied after PGE2, PGE2-induced increase in TTX-R INa (85.3 ± 19.6%) was not significantly different than the increase in the current induced by PGE2 alone. Preapplication of naloxone (10 μM) blocked DAMGO-induced inhibition of the PGE2-induced increase in TTX-R INa. DAMGO, alone, had no effect on peak TTX-R INa (1.4 ± 1.5% of baseline). Our observation that DAMGO prevents PGE2-induced potentiation of TTX-R INa is consistent with the suggestion that modulation of TTX-R INa underlies the hyperalgesic agent-induced increase in the excitability of nociceptors associated with sensitization and hyperalgesia. Furthermore, our data suggest that inhibition of hyperalgesic agent induced modulation of TTX-R INa may be a novel mechanism underlying opioid-induced antinociception.