Effects of peripheral electric stimulation on the central 5-hydroxytryptamine in mice: Relation to the peripheral stimulation-produced analgesia

Abstract

Effects of peripheral electric stimulation (PES) on the functional state of central 5-hydroxytryptamine (5-HT) and on the analgesic effect were investigated in mice. The PES was administered by a passing rectangular wave (0.45 mA, 5 msec, 5 ?? 100 Hz) for 2 hr through bipolar electrodes implanted subcutaneously at the base of the tail. Whole brain 5-HT concentration remained unchanged with the PES at 20 Hz, whereas 5-hydroxyindoleacetic acid concentrations were significantly increased in the whole brain. A significant increase in the whole brain compared with that in control was already attained at 30 min after initiation of the PES. Number of head-twitches induced by 5-methoxy-N, N-dimethyltryptamine after the PES was clearly potentiated. Increase in the number of head-twitches after the PES was abolished by administration of p-chlorophenylalanine, a 5-HT depletor, and 5, 6-dihydroxytryptamine, a 5-HT neurotoxin. The PES for I hr produced an antinociceptive effect. Administration of L-5-hydroxytryptophan enhanced the antinociceptive effect induced by PES, while methysergide and naloxone completely abolished this antinociception. Thus, 5-HT neurons are probably excited functionally by the PES, and the mechanisms of analgesia produced by the PES involve both endogenous opiate systems and central serotonergic mechanisms.