DAMGO INHIBITS PROSTAGLANDIN E(2)-INDUCED POTENTIATION OF A TTX-RESISTANT NA-VITRO( CURRENT IN RAT SENSORY NEURONS IN)

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) (P GE(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 gang lion 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-N a in the presence of 1 mu M DAMGO (24.9+/-7.7%), was significantly les s than that induced by PGE(2) alone. In contrast, when DAMGO was appli ed 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 induc ed 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). Ou r 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. Further more, our data suggest that inhibition of hyperalgesic agent induced m odulation of TTX-R I-Na may be a novel mechanism underlying opioid-ind uced antinociception.