Opposing actions of cimetidine on naloxone-sensitive and naloxone-insensitive forms of footshock-induced analgesia.

The effects of the opiate antagonist naloxone (10 mg/kg) and the histamine H2-antagonist cimetidine (100 mg/kg; both administered i.p.) were studied on the analgesia elicited by 3 currents of continuous-scrambled AC footshock (FSIA). Repeated analgesic measurements were made in each animal by use of the radiant heat tail-flick test. As shown by others, naloxone effectively inhibited the FSIA produced by 3 min of 2.0 mA, but had no effect on the responses elicited by higher currents (2.5 and 3.5 mA) of the same duration. Cimetidine significantly reduced the naloxone-insensitive FSIA after 3.5 mA, had no effect on that produced by 2.5 mA and potentiated the naloxone-sensitive analgesia elicited by 2.0 mA. These findings add to existing data supporting a role for brain histamine as a mediator of naloxone-insensitive analgesia, and also suggest the possibility that histamine may mediate hyperalgesic responses.