Analgesic effect of histamine induced by intracerebral injection into mice

Three methods were used to study the analgesic effect of intracerebral injection of histamine (Hi) on mice: the writhing test (acetic acid and phenylquinone), the electrical stimulation of the tail and the hot plate test. At doses higher than 2 micrograms, Hi inhibited the writhing syndrome significantly, and at doses of 10 micrograms or higher, Hi displayed a marked analgesic effect during both the electrical stimulation and hot plate methods. The saline injection produced only a negligible effect. Simultaneous application of Hi and 10 micrograms of diphenhydramine, pyrilamine or promethazine, apparently causing no analgesic effect from a single administration, caused a parallel shift of the dose-response curve of Hi to the right. ED50 of Hi was increased approximately 2, 2.8 and 3.8 times, respectively. However, cimetidine did not reveal any antagonistic effect on Hi-induced analgesia. Subcutaneously administered, 3 mg/kg of morphine augmented the analgesic effect of Hi. In accordance with this, pretreatment of naloxone (0.005 mg/kg) antagonized the analgesic action of Hi almost completely. When 5 mg/kg of leucine-enkephalin, less than the minimum effective dose, was given prior to Hi injection, the analgesic effect of Hi was enhanced. In addition, 10 and 20 micrograms of Hi increased the morphine analgesia markedly and parallel shifted the dose-response curve of morphine to the left.