Calcitonin and its antinociceptive activity: animal and human investigations 1975-1992.

Calcitonin (CT) is a polypeptide hormone produced in the thyroid gland that regulates, blood calcium levels and bone calcium metabolism. The unexpected finding of binding sites for calcitonin in several areas of the brain oriented attention to activities of CT in the central nervous system and also to its antinociceptive action. The first report of this last effect was in 1975, and the many different experimental and clinical data on this topic reported since then are reviewed here. The heterogenous findings have been organized according to the logical classification of animal and human studies. For each of these headings, subheadings such as acute and chronic pain, different kinds of administration and different procedures used to record the results, are considered. The several proposed mechanisms of action, involving serotoninergic, catecholaminergic, Ca2+ fluxes, protein phosphorylation, beta-endorphin production, cyclooxygenase inhibition and histamine interference are also reviewed. Calcitonin, neurotensin, substance P, VIP and, recently, CGRP are some of the non-opioid peptides that have been reported to interfere with pain and that open up a new, alternative way of investigating antinociceptive drugs different than opioid or opioid-like agents. An examination of the state-of-investigation of calcitonin's antinociceptive activity in the last 17 years shows that many experimental studies indicate the existence of this effect, including studies in humans, and this opens up perspectives for therapy with a new class of antinociceptive agents.