Salmon calcitonin potentiates the analgesia induced by antidepressants

Antidepressants are used in the treatment of a variety of pain syndromes. Most of them act by blocking noradrenaline (NA) and serotonin (5-HT) reuptake. It is also well known that the serotonergic system is also involved in calcitonin (CT) analgesia. Taking these two evidences into account, the modification of the analgesic effect of nortriptyline, amitriptyline, and paroxetine in the presence of salmon CT (s-CT) was examined in mice. The forced-swimming test was carried out in order to choose doses of each drug that did not induce an antidepressant effect under our experimental conditions (nortriptyline: 0.2-5 mg/kg ip, amitriptyline: 2.5-20 mg/kg ip, and paroxetine: 5-30 mg/kg ip). The analgesic effect of each antidepressant was then evaluated using the acetic acid test. At the doses tested, the antidepressants induced a dose-dependent analgesic effect. When mice were pre-treated with a subanalgesic dose of s-CT (2.5 IU/kg), the analgesic effect of amitriptyline and paroxetine was significantly increased though no modification was found for nortriptyline. In summary, s-CT was able to increase the analgesic effect of the antidepressant drugs that reduce the uptake of 5-HT, suggesting that the joint administration of antidepressants and CT may be an interesting alternative in pain management.