Involvement of brain serotonergic terminals in the antinociceptive action of peripherally applied calcitonin

We investigated the antinociceptive effect of systemic injection of calcito nin and its mechanisms of action in rats. Subcutaneous injection of [Asu(1, 7)]eel calcitonin (ECT, 4 U . kg(-1) . day(-1)) daily for 7 days suppressed nociceptive hypersensitivity induced by formalin land by carrageenan); the effect was gradually increased by the repeated injections and significant effects were observed after administration for more than 4 days. The antino ciceptive action of ECT (4U . kg(-1) . day(-1) for 7 days) was inhibited by intracerebroventricular injection of the serotonergic neurotoxin 5,7-dihyd roxytryptamine and serotonin-receptor antagonists methiothepin, cyproheptad ine and ketanserin; methysergide showed an inhibitory tendency. Intrathecal injections of 5,7-dihydroxytryptamine, methiothepin, cyproheptadine and ke tanserin were without effects on the ECT action. The results suggest the in volvement of serotonin in the brain, but not in the spinal cord, in the ECT antinociception. Intracerebroventricular or intrathecal injection of the c atecholaminergic neurotoxin 6-hydroxydopamine and intracerebroventricular i njection of the alpha-adrenoceptor antagonist phentolamine were also withou t effects on the ECT action. A subcutaneous infusion of the opioid receptor antagonist naloxone inhibited the antinociceptive action of morphine, but not that of ECT. Thus, adrenergic and opioidergic systems may not play impo rtant roles in the ECT antinociception. The present results suggest that re peated systemic injection of ECT produces analgesia and that the brain sero tonergic terminals are involved in this action.