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

Neurosci Lett. 1996 Jul 12;212(2):83-6. doi: 10.1016/0304-3940(96)12791-9.


We have tested the hypothesis that the mu-opioid agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (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 microM) induced a 103 +/- 22.8% increase in peak TTX-R INa. The PGE2-induced increase in TTX-R INa in the presence of 1 microM 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 microM) 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.

Publication types

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

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Dinoprostone / pharmacology*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalins / pharmacology*
  • In Vitro Techniques
  • Male
  • Neurons, Afferent / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channels / drug effects*
  • Tetrodotoxin / pharmacology


  • Analgesics
  • Enkephalins
  • Sodium Channels
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Tetrodotoxin
  • Dinoprostone