DAMGO inhibits prostaglandin E(2)-induced potentiation of a TTX-resistant Na+ current in rat sensory neurons in vitro

We have tested the hypothesis that the mu-opioid agonist, [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO), inhibits prostaglandin E(2) (PGE(2))-induced modulation of a tetrodotoxin-resistant voltage-gated Na+ current (TTX-R 1(Na)) in putative nociceptors in vitro. Patch-clamp electrophysiological techniques were used on cultured dorsal root ganglion neurons from the adult rat. PGE(2) (1 mu M) induced a 103+/-22.8% increase in peak TTX-R I-Na. The PGE(2)-induced increase in TTX-R I-Na in the presence of 1 mu M DAMGO (24.9+/-7.7%), was significantly less than that induced by PGE(2) alone. In contrast, when DAMGO was applied after PGE(2), PGE(2)-induced increase in TTX-R I-Na (85.3+/-19.6%) was not significantly different than the increase in the current induced by PGE(2) alone. Preapplication of naloxone (10 mu M) blocked DAMGO-induced inhibition of the PGE(2)-induced increase in TTX-R I-Na DAMGO, alone, had no effect on peak TTX-R I-Na (1.4+/-1.5% of baseline). Our observation that DAMGO prevents PGE(2)-induced potentiation of TTX-R I-Na is consistent with the suggestion that modulation of TTX-R I-Na 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 I-Na may be a novel mechanism underlying opioid-induced antinociception.