No tolerance to the antinociceptive action of calcitonin in rats and mice

The involvement of a central opioid mechanism in the antinociceptive effect of calcitonin is still a matter of controversy. Since a-major characteristic of the effects of opioids is tolerance to repeated treatments, we investigated the effects of acute and chronic (over 7 days) calcitonin injections on pain sensitivity in rats and mice. We examine the effect of single and repeated intraventricular (0.15 UI) and intraperitoneal (2.5, 5 and 20 IU/kg) injection of salmon calcitonin using respectively a tail flick test in rats and the writhing test in mice. The results showed that repeated injection of calcitonin produces a stronger antinociceptive effect than the single injection effect. The antalgic effect, evaluated in the writhing test, is dose-dependent. In both tail-immersion and writhing tests, repeated administration of calcitonin produced a long-lasting antinociceptive effect. These data suggest therefore that the tolerance does not develop after repeated treatment with calcitonin in both rat and mouse. These results support the hypothesis that an important component of the antinociceptive effects of calcitonin is not mediated by an opioid mechanism. (C) 2003 Elsevier Ireland Ltd. All rights reserved.