Jpn. J. Pharmacol. 81 (4), 367 - 374 (1999)

Involvement of Brain Serotonergic Terminals in the Antinociceptive
Action of Peripherally Applied Calcitonin

Nahoko Yamazaki¹, Hiroshi Umeno² and Yasushi Kuraishi^1,*


¹Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University,
Toyama 930 - 0194, Japan
²Institute for Life Science Research, Asahi Chemical Industry Co., Ohito, Shizuoka 410 - 2321, Japan
* To whom correspondence should be addressed.

Abstract: We investigated the antinociceptive effect of systemic injection of calcitonin 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 (and by carrageenan); the effect was gradually increased by the repeated injections and significant effects were observed after administration for more than 4 days. The antinociceptive action of ECT (4 U・kg^-1・day^-1 for 7 days) was inhibited by intracerebroventricular injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine and serotoninreceptor antagonists methiothepin, cyproheptadine and ketanserin; methysergide showed an inhibitory tendency. Intrathecal injections of 5,7-dihydroxytryptamine, methiothepin, cyproheptadine and ketanserin were without effects on the ECT action. The results suggest the involvement of serotonin in the brain, but not in the spinal cord, in the ECT antinociception. Intracerebroventricular or intrathecal injection of the catecholaminergic neurotoxin 6-hydroxydopamine and intracerebroventricular injection of the αadrenoceptor antagonist phentolamine were also without 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 important roles in the ECT antinociception. The present results suggest that repeated systemic injection of ECT produces analgesia and that the brain serotonergic terminals are involved in this action.

Keywords: Calcitonin analgesia, Nociceptive hypersensitivity, Serotonin, Noradrenaline, Opioid