Effect of synthetic eel calcitonin, elcatonin, on cold and mechanical allodynia induced by oxaliplatin and paclitaxel in rats.

Oxaliplatin and paclitaxel are commonly used anti-cancer drugs, but they frequently cause peripheral neuropathic pain. In this study, we investigated the effect of elcatonin, a synthetic eel calcitonin, on oxaliplatin- and paclitaxel-induced neuropathy in rats. The rats were treated with a single dose of oxaliplatin (6 mg/kg, i.p.) or repeated doses of paclitaxel (2 mg/kg, i.p.) on 4 alternate days. Both treatments resulted in cold and mechanical allodynia. We assessed the anti-allodynic effects of subcutaneously administered elcatonin (20 U/kg/day) by using a newly developed method to provide cold stimulation (8°C) directly to the hind paw of the rats and by using the von Frey test. Elcatonin almost completely reversed the effects of both cold and mechanical allodynia. To determine the mechanism of this anti-allodynic effect, we examined the effect of elcatonin on neuropathy induced by intraplantar injection of two organic compounds: allyl isothiocyanate (1 nmol/paw), which activates transient receptor potential ankyrin-1 channels, and menthol (1.28 μmol/paw), which activates transient receptor potential ankyrin-1 and melastatin-8. Pre-administration of elcatonin almost completely prevented cold and mechanical allodynia from being induced by both compounds. These results suggest that elcatonin attenuates oxaliplatin- and paclitaxel-induced neuropathic pain by inhibiting the cellular signaling related to transient receptor potential ankyrin-1 and melastatin-8. Thus, we conclude that administration of elcatonin may improve the quality of life of cancer patients receiving chemotherapy.