Endogenous antinociceptive mechanisms

Histamine also induces antinociceptive (i.e. pain-relieving) responses in animals after microinjection into several brain regions [73, 74]. H, and H2 mechanisms are significant and both neuronal and humoral mechanisms may be involved. Brain H2 receptors appear to mediate some forms of endogenous analgesic responses, especially those elicited by exposure to stressors [75]. Many of the modulatory actions of histamine discussed above appear to be activated as part of stress responses. For reasons that remain unclear, histamine releasers, such as thioperamide, show only mild, biphasic antinociceptive actions, even though histamine is a potent and effective analgesic substance. Outside the brain, both H and H3 receptors exist on certain types of sensory nerves and activation of these receptors promotes and inhibits, respectively, peripheral nerve transmission related to pain and/or inflammation [76,77]. 

Recently, the endogenous morphine receptor ligand, enkephalin, has been iso= lated [305], identified chemically [306], and found to possess antinociceptive activity in mice after ICV injection [307], The interactions of the amines, enkephalin, and the cyclic nucleotides remain to be determined, and the scope for future studies of the mechanisms of action of the opiate analgesics becomes much wider as a result of these more recent studies. 

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