Melatonin, the hormone of darkness has many physiological functions in the body and also exerts a number of pharmacological effects. Most of these actions of melatonin are mediated through melatonin membrane receptors like MT1/MT2 receptors or through nuclear orphan receptors like RZR/ROR receptors or through calcium binding proteins in the cytosol. The finding that pain perception is circadian in nature has prompted many to suggest that "pain modulation" is one of the most important physiological functions of melatonin. By using a number of animal models of pain perception, it has been found that melatonin exerts antinociceptive and antiallodynic effects. Number of studies has shown that melatonin modulates pain perception by acting through opioid receptors, NMDA receptors and G-protein, and they have been analyzed using specific antagonists like naloxone or NMDA-G protein receptor antagonists. Recently it has been shown that melatonin exerts its antinociceptive effects through MT1 and MT2 melatonergic receptors located in the dorsal region of the spinal cord as well as in various parts of the brain concerned with pain modulation. Evidences for this have been obtained by using common melatonergic receptor antagonist like luzindole or specific MT2 receptor antagonist like 4P-PDOT or K-185. In a few clinical studies undertaken during surgery, melatonin has been shown to have analgesic effects. Melatonin is emerging as a new analgesic drug with a novel mechanism of actions and has the potential to be used as a natural pain killer in inflammatory, neuropathic pain conditions and also during surgical procedures.

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褪黑素及其激动剂在疼痛调节中的作用及其临床应用。

褪黑激素，一种黑暗激素，在人体中具有许多生理功能，并且还具有许多药理作用。褪黑激素的大多数这些作用是通过褪黑激素膜受体（如MT1 / MT2受体）或核孤儿受体（如RZR / ROR受体）或胞浆中的钙结合蛋白介导的。疼痛感觉本质上是昼夜节律的发现促使许多人提出“疼痛调节”是褪黑激素最重要的生理功能之一。通过使用多种疼痛感知的动物模型，发现褪黑激素具有抗伤害感受和抗痛觉过敏作用。大量研究表明，褪黑素通过阿片受体，NMDA受体和G蛋白的作用来调节疼痛感，并且已使用诸如纳洛酮或NMDA-G蛋白受体拮抗剂之类的特异性拮抗剂进行了分析。最近已经表明，褪黑激素通过位于脊髓背侧区域以及与疼痛调节有关的大脑各个部位的MT1和MT2褪黑素能受体发挥抗伤害作用。通过使用常见的褪黑激素受体拮抗剂（如luzindole）或特定的MT2受体拮抗剂（如4P-PDOT或K-185）已获得了证据。在外科手术期间进行的一些临床研究中，褪黑激素已显示出止痛作用。褪黑激素作为一种具有新型作用机制的新型镇痛药正在出现，并有潜力在炎症性，神经性疼痛以及手术过程中用作天然止痛药。