Nociceptive responses in melatonin MT<sub>2</sub> receptor knockout mice compared to MT<sub>1</sub> and double MT<sub>1</sub>/MT<sub>2</sub> receptor knockout mice
Luca Posa, Martha López-Canul, Laura Rullo, Danilo De Gregorio, Sergio Domínguez-López, Matthew Kaba Aboud, Francesca Felicia Caputi, Sanzio Candeletti, Patrizia Romualdi, Gabriella Gobbi
Abstract
Abstract Melatonin, a neurohormone that binds to two G protein‐coupled receptors MT 1 and MT 2, is involved in pain regulation, but the distinct role of each receptor has yet to be defined. We characterized the nociceptive responses of mice with genetic inactivation of melatonin MT 1 (MT 1 −/− ), or MT 2 (MT 2 −/− ), or both MT 1 /MT 2 (MT 1 −/− /MT 2 −/− ) receptors in the hot plate test (HPT), and the formalin test (FT). In HPT and FT, MT 1 −/− display no differences compared to their wild‐type littermates (CTL), whereas both MT 2 −/− and MT 1 −/− /MT 2 −/− mice showed a reduced thermal sensitivity and a decreased tonic nocifensive behavior during phase 2 of the FT in the light phase. The MT 2 partial agonist UCM924 induced an antinociceptive effect in MT 1 −/− but not in MT 2 −/− and MT 1 −/− /MT 2 −/− mice. Also, the competitive opioid antagonist naloxone had no effects in CTL, whereas it induced a decrease of nociceptive thresholds in MT 2 −/− mice. Our results show that the genetic inactivation of melatonin MT 2 , but not MT 1 receptors, produces a distinct effect on nociceptive threshold, suggesting that the melatonin MT 2 receptor subtype is selectively involved in the regulation of pain responses.