Melatonin, a neurohormone that binds to two G protein‐coupled receptors MT₁ 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 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.

中文翻译：

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与 MT1 和双 MT1/MT2 受体敲除小鼠相比，褪黑激素 MT2 受体敲除小鼠的伤害性反应。

褪黑激素是一种与两种 G 蛋白偶联受体 MT ₁和 MT ₂结合的神经激素，参与疼痛调节，但每种受体的不同作用尚未确定。我们表征了具有褪黑激素 MT ₁ (MT ₁ ^-/- ) 或 MT ₂ (MT ₂ ^-/- ) 或 MT ₁ /MT ₂ (MT ₁ ^-/- /MT ₂ ^- )基因失活的小鼠的伤害感受反应^/- ) 热板试验 (HPT) 和福尔马林试验 (FT) 中的受体。在 HPT 和 FT 中，MT ₁ ^-/-与它们的野生型同窝仔 (CTL) 相比没有显示差异，而 MT ₂ ^-/-和 MT ₁ ^-/- /MT ₂ ^-/-小鼠在治疗的第 2 阶段期间表现出降低的热敏感性和降低的强直伤害行为FT 在轻相。MT ₂部分激动剂UCM924在MT ₁ ^-/-但不在MT ₂ ^-/-和MT ₁ ^-/- /MT ₂ ^-/-小鼠中诱导镇痛作用。此外，竞争性阿片类拮抗剂纳洛酮对 CTL 没有影响，但它诱导 MT ₂ ^-/-中伤害感受阈值的降低老鼠。我们的结果表明，褪黑激素 MT ₂而非 MT ₁受体的遗传失活对伤害感受阈值产生明显影响，表明褪黑激素 MT ₂受体亚型选择性地参与了疼痛反应的调节。