ANTINOCICEPTIVE EFFECTS OF MORPHINE WERE DIFFERENT BETWEEN EXPERIMENTAL AND GENETIC DIABETES

This study was designed to investigate the effect of morphine on forma lin-induced nociceptive responses in streptozotocin (STZ) induced-diab etic mice, noninsulin-dependent genetically diabetic db/db mice and th eir respective controls (ddY and +/+). In nondiabetic (ddY and +/+) mi ce, morphine (1-10 mg/kg, PO) dose dependently attenuated the biphasic nociceptive responses induced by SC injection of formalin to the hind paw, demonstrating equipotency on both the first and second phases. Pa ra-chlorophenylalanine (800 mg/kg x 2, PO) and pindolol (1 mg/kg, IF) reduced the effect of morphine on the first phase, sulpiride (10 mg/kg , IF) abolished the effect on both phases, while ketanserin (1 mg/kg, IF) had no effect. In STZ (200 mg/kg, IP)-diabetic mice, morphine weak ly attenuated the nociception in comparison to control ddY mice, where as it had comparable effects in both the first and second phases of co ntrol +/+ mice and db/db mice. The serotonergic agonist, meta-chloroph enylpiperazine (0.32-3.2 mg/kg, PO), dose dependently attenuated the b iphasic nociceptive responses to formalin in both phases of diabetic m ice; however, FR64822, a dopaminergic compound (0.1-10 mg/kg, PO), had little effect. We speculate that activation of both dopaminergic (DA) - and serotonergic-mediated mechanisms are potentially responsible for the effect of morphine on the first phase, while the DA-mediated effe ct is involved in the second phase. The DA-mediated mechanism, but not the serotonin-mediated one, appears to be altered in both STZ-diabeti c and db/db mice. These results suggest that the attenuated effects of morphine might be due to a dopaminergic dysfunction in STZ mice, and that there might be other mechanisms compensating for this attenuation of dopaminergic function in db/db mice. (C) 1998 Elsevier Science Inc .