The interaction between IL-1beta 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 of morphine. Some factor(s) derived from mononuclear cells, e.g. interleukin-1beta (IL-1beta), may be responsible for the diminished analgesic effect of morphine in diabetic mice. Therefore, we examined direct effects of IL-1beta, 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 sensitive to the analgesic effect of morphine when compared to the controls. IL-1beta at a dose of 0.1 ng/mouse produced analgesia in control mice but not in diabetics, whereas IL-1beta at a dose of 10 ng/mouse produced a hyperalgesic effect both in diabetic and control mice. IL-1beta at a dose of 1 ng/mouse has neither an analgesic nor a hyperalgesic effect in control and diabetic mice. Administration of a neutral (neither analgesic nor hyperalgesic) dose of IL-1beta, 1 ng/mouse (i.c.v.), just prior to administration of morphine (s.c.) abolished the analgesic effect of morphine at doses of 1, 2 and 5 mg/kg in control mice and the analgesic effect of morphine became similar to that in diabetics. The diminished analgesic effect of morphine in diabetes was attenuated further with IL-1beta 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-1beta.
Gul
Husamettin
H
Department of Pharmacology, School of Medicine, Gulhane Military Medical Academy, 06018, Etlik, Ankara, Turkey.
Yildiz
Oguzhan
O
Dogrul
Ahmet
A
Yesilyurt
Ozgur
O
Isimer
Askin
A
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D012007:Rectum; D013623:Tail
D000701:Analgesics, Opioid; D007375:Interleukin-1; D009020:Morphine