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 mu M tetrodotoxin, the application of 3 mu M capsaicin to spinal dorsal horn slices produced an evoked glutamate release (55.9 +/- 4.02 pmol . mg(-1)protein, n = 15). DAMGO ([D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin; 0.3-10 mu M) and morphine (1-30 mu M), mu-opioid agonists, produced a concentration-dependent reduction (similar to 85 and similar to 77% reduction, respectively) in the capsaicin (3 mu M)-evoked release of glutamate. These inhibitory effects were significantly antagonized by naloxone (1 mu M) DPDPE ([D-Pen(2,5)]enkephalin; 1-10 mu M), a delta-opioid agonist, also reduced the capsaicin-evoked release in a concentration-dependent manner (similar to 59% reduction). Naltrindole (1 mu M), a selective delta-antagonist, significantly antagonized the inhibitory effect of DPDPE (10 mu M). In contrast, neither U-50,488H (1-10 mu M) nor U-69,593 (10 mu M), 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.