Serum glucose level-dependent and independent modulation of mu-opioid agonist-mediated analgesia in diabetic mice.
We examined the effect of insulin on the analgesic potency of DAMGO, a selective agonist of mu-opioid receptors, in mice which had been rendered diabetic by an injection of streptozotocin (STZ; 200 mg/kg, i.v.) 1 and 2 weeks previously. The analgesic potency of DAMGO, based on the tail-flick test, was significantly decreased in both the 1 and 2-week diabetic mice as compared to its effect in age-matched controls. Sensitivity to the analgesic potency of DAMGO returned to normal when insulin was administered to STZ-induced 1-week diabetic mice. However, pretreatment with insulin had no significant effect on the sensitivity to the analgesic potency of DAMGO in 2-week diabetic mice. These results suggest that the serum glucose levels may possibly be responsible for the altered potency of mu-opioid agonists only during the incipient stages of diabetes.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
J
J
Kamei
N
N
Kawashima
Y
Y
Kasuya
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D001786:Blood Glucose; D004745:Enkephalins; D007328:Insulin; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-