Antinociceptive effects of repeated systemic injections of calcitonin in formalin-induced hyperalgesic rats

Calcitonin (CT) produces long-lasting analgesia in patients suffering from painful diseases following repeated systemic injections, but there have been only a few contradictory reports on the antinociceptive action of systemic injections of CTs in animal experiments. This study was conducted to elucidate an antinociceptive action of systemic CT in rats. An injection of dilute formalin induced hyperalgesia for about 2 h. Single topical injections of 0.12 and 1.2 U, but not 0.012 U, of [Asu1.7] eel CT (eCT) into the same site of formalin injection inhibited the hyperalgesia. Repeated systemic injections of eCT (4 and 40, but not 0.4, U kg-1 day-1) for 7 days inhibited the hyperalgesia, while the single injection was without effects at doses tested. Although the highest dose of eCT (40 U kg-1 day-1) inhibited an increase in body weight following repeated injections, lower doses (0.4 and 4 U kg-1 day-1) were without effects. The suppression of hyperalgesia following repeated systemic injections of eCT (4 U kg-1 day-1) lasted for at least 24 h, and subsided by 3 days following the last eCT injection. These results indicate that the repeated systemic injections of eCT produce a long-lasting inhibition of formalin-induced hyperalgesia in rats. This inhibitory effect is similar to CT analgesia in human subjects in terms of a necessity for repeated administration, effective dose and long-lasting effects.