Alpha 2-adrenoceptor-mediated inhibition of capsaicin-evoked release of glutamate from rat spinal dorsal horn slices.

It is known that the descending noradrenergic system suppresses nociceptive transmission in the spinal dorsal horn. To determine whether noradrenaline-alpha-adrenoceptor systems exert inhibitory influence on the release of glutamate from the nociceptive primary afferents, the effects of alpha-adrenoceptor agonists on the capsaicin (3 microM)-evoked release of glutamate from rat spinal dorsal horn slices were examined using an on-line continuous monitoring system for glutamate. The application of alpha 2-agonists clonidine (0.1-10 microM) and ST-91 (1 and 10 microM), respectively, decreased the capsaicin-evoked release of glutamate in a concentration-dependent manner. The partial alpha 2-agonist oxymetazoline (1 and 10 microM) produced a slight inhibition in the evoked release of glutamate. In contrast, the alpha 1-agonist phenylephrine (1 and 10 microM) did not show any significant effects on the evoked release of glutamate. The inhibitory action of 10 microM clonidine on the evoked glutamate release was antagonized by the alpha 2-antagonist yohimbine (1 microM) but not by the opioid antagonist naloxone (10 microM). These findings suggest that noradrenaline, probably released from the descending inhibitory system, reduces the release of glutamate from the capsaicin-sensitive primary afferent terminals through alpha 2-adrenoceptors.