Opioidergic inhibition of capsaicin-evoked release of glutamate from rat spinal dorsal horn slices.

We investigated the effects of opioid agonists on the capsaicin-evoked release of glutamate from nociceptive primary afferent fibers of the rat (6-8 weeks) using a fluorometric on-line continuous monitoring system for glutamate. In the presence of 0.3 microM tetrodotoxin, the application of 3 microM capsaicin to spinal dorsal horn slices produced an evoked glutamate release (55.9 +/- 4.02 pmol.mg-1 protein, n = 15). DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin; 0.3-10 microM) and morphine (1-30 microM), mu-opioid agonists, produced a concentration-dependent reduction (approximately 85 and approximately 77% reduction, respectively) in the capsaicin (3 microM)-evoked release of glutamate. These inhibitory effects were significantly antagonized by naloxone (1 microM). DPDPE ([D-Pen2,5]enkephalin; 1-10 microM), a delta-opioid agonist, also reduced the capsaicin-evoked release in a concentration-dependent manner (approximately 59% reduction). Naltrindole (1 microM), a selective delta-antagonist, significantly antagonized the inhibitory effect of DPDPE (10 microM). In contrast, neither U-50,488H (1-10 microM) nor U-69,593 (10 microM), kappa-opioid agonists, had any effects on the evoked release of glutamate. These results suggest that mu-, and delta-opioid agonists modulate pain transmission in the spinal dorsal horn, at least in part, by inhibiting the release of glutamate from capsaicin-sensitive primary afferents.