Hyperalgesic response to noxious stimulation in genetically polydipsic mice.

Inbred mice, STR/N, are known to exhibit extreme polydipsia and polyuria but no abnormality in the response to exogenous vasopressin (AVP) and renal functions. Our previous studies have revealed that the brain opioid system is involved in the polydipsia of these mice. We here report that the STR/N mice show a decrease in the nociceptive threshold and a low, anti-nociceptive sensitivity to opioid receptors agonists. The paw-withdrawal latency (PWL) on a hot-plate in the STR/N mice was significantly shorter than that in their controls (BALB/c and C3H mice). This hyperalgesia was not affected by water restriction. Subcutaneous (s.c.) injections of morphine (5 mg/kg) and a kappa-opioid receptor agonist, U50,488H (16 mg/kg) had no effect on the PWL in the STR/N mice, whereas the control mice prolonged PWL after administration of the opioids. However, the STR/N mice gained the ability to show morphine analgesia after up-regulation of the opioid system by repeated administration of naltrexone (s.c., 5 mg/kg) for 3 consecutive days. The results suggest that the anti-nociceptive function of the opioid system is down-regulated in STR/N mice as is observed in chronic morphine-treated animals.