Capsaicin selectively excites nociceptive primary afferent fibers and increases the frequency of glutaminergic miniature excitatory postsynaptic currents (mEPSCs) in the substantia gelatinosa of the spinal dorsal horn. The whole-cell voltage-clamp recording technique was used to examine the effect of norepinephrine (NE) on the capsaicin-induced increase in the frequency of mEPSCs. In the presence of tetrodotoxin, bath application of capsaicin (1 microM) remarkably enhanced the frequency of mEPSCs (295+/-52% of control). Following pretreatment with NE (10 microM), the capsaicin-induced frequency facilitation of mEPSCs was significantly depressed to 151+/-17% of the control. NE-induced depression in capsaicin action was blocked by yohimbine, a selective alpha(2)-adrenergic receptor antagonist, indicating that NE exerts depression by activating the alpha(2)-adrenergic receptor. As the postsynaptic action of NE has been precluded in the present study, the results suggest that NE inhibits nociceptive input at a presynaptic site, the primary afferent terminal, during the nociceptive transmission in the spinal dorsal horn.
Adrenergic alpha-Agonists Animals