The central serotonergic system mediates the analgesic effect of electroacupuncture on ZUSANLI (ST36) acupoints

Evidence in the past decade indicates that the mechanisms of anti-nociception of electroacupuncture (EAc) involve actions of neuropeptides (i.e., enkephalin and endorphin) and monoamines (i.e., serotonin and norepinephrine) in the central nervous system. Our present results using a subcutaneous injection of formalin to test pain sensation in mice provide further understanding of the involvement of serotonin in the actions of EAc-induced analgesia. Our observations show that (1) EAc at three different frequencies (2, 10 and 100 Hz) elicited an anti-nociceptive effect as determined by behavioral observations of reduced hindpaw licking; (2) exogenously intracerebroventricular administration of 5-hydroxytryptamine (5-HT) exhibited an analgesic effect, which partially mimicked the analgesic actions of EAc; (3) the anti-nociception of EAc at different frequencies was attenuated after reduced biosynthesis of serotonin by the administration of the tryptophan hydroxylase inhibitor, P-chlorophenylalanine, and (4) the 5-HT(1A) and 5-HT(3) receptor antagonists, pindobind-5-HT(1A) and LY-278584, respectively, blocked three different frequencies of EAc-induced analgesic effects, but the anti-nociceptive effect of 100 Hz EAc was potentiated by the 5-HT(2) receptor antagonist, ketanserin. These observations suggest that 5-HT(1A) and 5-HT(3) receptors partially mediate the analgesic effects of EAc, but that the 5-HT(2) receptor is conversely involved in the nociceptive response.