The analgesic effect induced by repeated administration of histamine and histamine liberators.

Much information has now accumulated which favors the idea that histamine participates in the peripheral sensory function. Kwiatkowski (1) has shown that sensory nerve fibers of the skin is more rich in histamine than the motor nerve fibers and has further demonstrated directly that histamine is liberated after antidromic stimulation of the sensory nerve trunks. Experimental evidences have been supplied by many other workers (2-9), suggesting some relation of histamine to the conduction of stimulus in peripheral sensory nerves. Rosenthal and his associates (10-14) developed the theory that histamine is liberated from the skin by various external stimuli and this substance transmits the stimulus to the sensory nerve endings. Another possible indication of the role of histamine in peripheral sensory mechanism is the analgesia developed during desensitization of histamine. Jacob, Ambrus and Ambrus (15) observed that a daily subcutaneous injection of histamine in a rat resulted in the decrease of pain reaction against thermal or electric stimulation of the tail or the paws, besides the decrease of sensitivity to histamine. However, these workers did not give any clear explanation of its mechanism. Jabob and Szerb (16), who observed the same fact in mice, assumed the involvement of pituitary-adrenal system in this phenomenon but did not offer sufficient evidence to justify their assumption. The present writer has confirmed the occurrence of analgesia as a result of daily sub cutaneous injection of histamine in mice and further, found similar analgesia to develop by daily injection of histamine liberators, in spite of the fact that the animals in this case became more susceptible to histamine contrary to the case of histamine desensitization. The present paper describes the results of some experiments carried out in order to elucidate the mechanism of these phenomena and may offer a new suggestion to the significance of histamine in the cutaneous pain mechanism.