Hyperalgesic response to noxious stimulation in genetically polydipsic mice

Inbred mice, STR/N, are known to exhibit extreme polydipsia and polyuria bu t no abnormality in the response to exogenous vasopressin (AVP) and renal f unctions. Our previous studies have revealed that the brain opioid system i s involved in the polydipsia of these mice. We here report that the STR/N m ice show a decrease in the nociceptive threshold and a low, anti-nociceptiv e 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 t heir 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 adminis tration of the opioids. However, the STR/N mice gained the ability to show morphine analgesia after up-regulation of the opioid system by repeated adm inistration of naltrexone (s.c., 5 mg/kg) for 3 consecutive days. The resul ts 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. (C) 1999 Elsevier Science B.V. All rights reserved.