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Nociceptive responses in melatonin MT 2 receptor knockout mice compared to MT 1 and double MT 1 /MT 2 receptor knockout mice
Author(s) -
Posa Luca,
LopezCanul Martha,
Rullo Laura,
De Gregorio Danilo,
DominguezLopez Sergio,
Kaba Aboud Matthew,
Caputi Francesca Felicia,
Candeletti Sanzio,
Romualdi Patrizia,
Gobbi Gabriella
Publication year - 2020
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12671
Subject(s) - melatonin , nociception , receptor , knockout mouse , medicine , endocrinology , agonist , melatonin receptor , chemistry , ctl* , ratón , biology , pharmacology , biochemistry , in vitro , cytotoxic t cell
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.