阿片药物仍是现今临床应用最广泛的镇痛药物，但其对神经病理性疼痛较低的镇痛效应限制了其在神经病理性疼痛镇痛中的应用。前期的研究表明，神经损伤后神经传导通路上的Mu阿片受体表达降低是引起上述现象的主要原因。该表达降低由翻译后调控机制和转录调控机制共同参与，但是具体的转录调控机制仍不清楚。已有的研究和我们的预试验均提示，DNA甲基化修饰可能是神经损伤后Mu阿片受体表达降低具体的转录调控机制。为此，本研究拟制备慢性坐骨神经缩窄性损伤模型，采用热辐射测痛，western-blot,qRT-PCR，激光共聚焦显微技术，siRNA，亚硫酸氢盐修饰后测序等技术，深入研究神经损伤后DNA甲基化修饰与神经损伤后Mu阿片受体表达降低的关系；以DNA甲基化修饰为靶点，进一步阐明阿片药物对神经病理性疼痛镇痛效应降低的具体生物学机制，有助于揭示神经病理性疼痛的发病机制并对其治疗提供新思路。

Today, opioids is still the most widely used analgesic drug in clinical. But the low analgesic effect limits its use in the application of neuropathic pain. It has been showed that the main reason of this decreased anagesia is due to the loss of Mu opioid receptor in the nerve conduction pathway. This decreased expression of Mu opioid receptor includes two mechanisms: the post-translational mechanism and the transcriptional mechanism, but the specific transcriptional mechamism is still unclear. Previous studies and our preliminary work showed that the DNA methylation mechanism might be the specific transcriptional mechanism which contributes to decreased expression of Mu opioid receptor after nerve injury. Therefore, with methods of thermal radiation for pain mesurement, western-blot, qRT-PCR, laser-confocal microscopy, siRNA and BSP,we will fouse on DNA methylation to further elucidate the specific mechanism of the low analgesia effect of opioids in neuropathic pain in the chronic constriction injury (CCI) model. It is our goal to to identify DNA methylation as the key step of the mechanism, which is helpful to reveal the mechanism of neuropathic pain, and provide scientific evidence for new therapeutic target.