ANTINOCICEPTIVE EFFECTS OF REPEATED SYSTEMIC INJECTIONS OF CALCITONININ FORMALIN-INDUCED HYPERALGESIC RATS

Calcitonin (CT) produces long-lasting analgesia in patients suffering from painful diseases following repeated systemic injections, but ther e have been only a few contradictory reports on the antinociceptive ac tion of systemic injections of CTs in animal experiments. This study w as 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 [ Asu(1,3)]eel CT (eCT) into the same site of formalin injection inhibit ed the hyperalgesia. Repeated systemic injections of eCT (4 and 40, bu t not 0.4, U kg(-1) day(-1)) for 7 days inhibited the hyperalgesia, wh ile the single injection was without effects at doses tested. Although the highest dose of eCT (40 U kg(-1) day(-1)) inhibited an increase i n 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)) las ted for at least 24 h, and subsided by 3 days following the last eCT i njection. These results indicate that the repeated systemic injections of eCT produce a long-lasting inhibition of formalin-induced hyperalg esia in rats. This inhibitory effect is similar to CT analgesia in hum an subjects in terms of a necessity for repeated administration, effec tive dose and long-lasting effects.