The interaction between IL-1 beta and morphine: possible mechanism of the deficiency of morphine-induced analgesia in diabetic mice

It is known that diabetic mice are less sensitive to the analgesic effect o f morphine. Some factor(s) derived from mononuclear cells, e.g. interleukin -1 beta (IL-1 beta), may be responsible for the diminished analgesic effect of morphine in diabetic mice. Therefore, we examined direct effects of IL- I beta, intracerebroventricularly (i.c.v.), on morphine-induced analgesia, subcutaneously (s.c.), in diabetic and control mice by using the tail-flick test. Morphine at doses of 1, 2 and 5 mg/kg (s.c.) produced dose-dependent analgesia in diabetic and control mice but diabetic mice were less sensiti ve to the analgesic effect of morphine when compared to the controls. IL-1 beta at a dose of 0.1 ng/mouse produced analgesia in control mice but not i n diabetics, whereas IL-1 beta at a dose of 10 ng/mouse produced a hyperalg esic effect both in diabetic and control mice. IL-I beta at a dose of 1 ng/ mouse has neither an analgesic nor a hyperalgesic effect in control and dia betic mice. Administration of a neutral (neither analgesic nor hyperalgesic ) dose of IL-I beta, 1 ng/mouse (i.c.v.), just prior to administration of m orphine (s.c.) abolished the analgesic effect of morphine at doses of i, 2 and 5 mg/kg in control mice and the analgesic effect of morphine became sim ilar to that in diabetics. The diminished analgesic effect of morphine in d iabetes was attenuated further with IL-1 beta at a dose of 1 ng/mouse (i.c. v.). These results suggest that the decreased analgesic effect of morphine in diabetes may be related to IL-1 beta. (C) 2000 international Association for the Study of Pain. Published by Elsevier Science B.V. All rights reser ved.