ALPHA2-ADRENOCEPTOR-MEDIATED INHIBITION OF CAPSAICIN-EVOKED RELEASE OF GLUTAMATE FROM RAT SPINAL DORSAL HORN SLICES

It is known that the descending noradrenergic system suppresses nocice ptive transmission in the spinal dorsal horn. To determine whether nor adrenaline-alpha-adrenoceptor systems exert inhibitory influence on th e release of glutamate from the nociceptive primary afferents, the eff ects of alpha-adrenoceptor agonists on the capsaicin (3 mu M)-evoked r elease of glutamate from rat spinal dorsal horn slices were examined u sing an on-line continuous monitoring system for glutamate. The applic ation of alpha(2)-agonists clonidine (0.1-10 mu M) and ST-91 (1 and 10 mu M), respectively, decreased the capsaicin-evoked release of glutam ate in a concentration-dependent manner. The partial alpha(2)-agonist oxymetazoline (1 and 10 mu M) produced a slight inhibition in the evok ed release of glutamate. In contrast, the alpha(1)-agonist phenylephri ne (1 and 10 mu M) did not show any significant effects on the evoked release of glutamate. The inhibitory action of 10 mu M clonidine on th e evoked glutamate release was antagonized by the alpha(2)-antagonist yohimbine (1 mu M) but not by the opioid antagonist naloxone (10 mu M) . These findings suggest that noradrenaline, probably released from th e descending inhibitory system, reduces the release of glutamate from the capsaicin-sensitive primary afferent terminals through alpha(2)-ad renoceptors.