1. Nociceptive responses in melatonin MT 2 receptor knockout mice compared to MT 1 and double MT 1 /MT 2 receptor knockout mice
- Author
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Francesca Felicia Caputi, Danilo De Gregorio, Matthew Kaba Aboud, Martha Lopez-Canul, Luca Posa, Gabriella Gobbi, Sanzio Candeletti, Patrizia Romualdi, Sergio Dominguez-Lopez, and Laura Rullo
- Subjects
musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,medicine.drug_class ,Chemistry ,macromolecular substances ,Partial agonist ,Melatonin ,03 medical and health sciences ,CTL ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,Nociception ,stomatognathic system ,Internal medicine ,embryonic structures ,Knockout mouse ,medicine ,Hot plate test ,Receptor ,030217 neurology & neurosurgery ,Opioid antagonist ,medicine.drug - Abstract
Melatonin, a neurohormone that binds to two G protein-coupled receptors MT1 and MT2, 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 MT1 (MT1 -/- ), or MT2 (MT2 -/- ), or both MT1 /MT2 (MT1 -/- /MT2 -/- ) receptors in the hot plate test (HPT), and the formalin test (FT). In HPT and FT, MT1 -/- display no differences compared to their wild-type littermates (CTL), whereas both MT2 -/- and MT1 -/- /MT2 -/- mice showed a reduced thermal sensitivity and a decreased tonic nocifensive behavior during phase 2 of the FT in the light phase. The MT2 partial agonist UCM924 induced an antinociceptive effect in MT1 -/- but not in MT2 -/- and MT1 -/- /MT2 -/- mice. Also, the competitive opioid antagonist naloxone had no effects in CTL, whereas it induced a decrease of nociceptive thresholds in MT2 -/- mice. Our results show that the genetic inactivation of melatonin MT2 , but not MT1 receptors, produces a distinct effect on nociceptive threshold, suggesting that the melatonin MT2 receptor subtype is selectively involved in the regulation of pain responses.
- Published
- 2020