Norepinephrine depresses the capsaicin-evoked miniature excitatory postsynaptic currents in substantia gelatinosa of the rat spinal cord

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 μM) remarkably enhanced the frequency of mEPSCs (295 ± 52% of control). Following pretreatment with NE (10 μM), 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 α₂-adrenergic receptor antagonist, indicating that NE exerts depression by activating the α₂-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.