The study found that melatonin activates antagonistic morphine analgesia tolerance by inhibiting NLRP3 inflammatory glands.

Recently, Yao Yonggang, a researcher at Kunming Institute of zoology, Chinese Academy of Sciences, published a research paper on the topic of melatonin alleviates morphine analgesic tolerance in mice by decreasing NLRP3 inflammasome activation on redox biology.this study found that melatonin could inhibit the activation of NLRP3 inflammasome induced by morphine, thus antagonizing morphine analgesia tolerance, and elucidated the molecular mechanism that melatonin combined with morphine can improve the analgesic effect of morphine and alleviate the analgesic tolerance induced by long-term morphine use.pain is a major disease affecting human health and one of the most common clinical diseases, affecting people's quality of life.morphine is a widely used analgesic in clinical practice, but long-term use can cause side effects such as pain tolerance and addiction. It is urgent to find drugs that can alleviate the side effects of morphine analgesia tolerance.melatonin has antioxidant and anti-inflammatory effects.previous animal studies have shown that pretreatment with melatonin in cells and mice can rescue morphine induced mitochondrial dysfunction, and then rescue morphine induced autophagy, and finally block morphine induced analgesia tolerance behavior (Feng et alet al. 2013. Autophagy 9:1395-406）。but can melatonin enhance the analgesic effect of morphine in a mouse model of morphine tolerance? If effective, the specific molecular mechanism of melatonin antagonizing morphine tolerance has not been elucidated.researchers have carried out systematic research from molecular, cellular and mouse animal models.it has been found that melatonin treatment can still alleviate morphine analgesia tolerance in mice models that have developed morphine tolerance.further studies showed that chronic morphine injection could increase the activity of oxidative free radicals (ROS), increase the release of cathepsin B (CTSB), and induce the activation of NLRP3 inflammasome; pre injection of melatonin could inhibit the activation of NLRP3 inflammasome, and finally alleviate the formation of morphine tolerance.at the same time, morphine combined with melatonin can improve the analgesic effect of the same dose of morphine.this study further elaborated the molecular mechanism of melatonin antagonizing morphine analgesia tolerance, which is expected to provide theoretical basis and reference for exploring the combination of melatonin and morphine in clinical analgesia practice.Liu Qianjin, a doctoral student of Yao Yonggang's research group, and Su Lingyan, an associate researcher of Yao Yonggang's research group, are the co first authors of the paper, and Yao Yonggang and Su Lingyan are the co corresponding authors of the paper.the research was supported by Zheng Ping, a researcher at Kunming Institute of zoology, and Xue Tian, Xiong Wei and Zhou Rongbin, professors of China University of science and technology.the research work is supported by the National Natural Science Foundation of China, the leading project of brain functional connectivity mapping of Chinese Academy of Sciences, and the frontier key research projects. melatonin inhibits the activation of NLRP3 inflammasome and blocks morphine analgesia tolerance. Source: Kunming Institute of zoology, Chinese Academy of Sciences