镇痛药是一类主要作用于中枢神经系统（CNS），能选择性地缓解或消除疼痛及伴随的不愉快情绪（如恐惧、紧张、焦虑等）的药物。由于镇痛药的CNS活性和对μ阿片受体的作用，存在依赖性潜在风险，已成为全球性公共卫生领域的重要问题。作为多成因的疾病，遗传学因素、神经系统因素、表观遗传因素、性别因素和环境差异都可能是镇痛药诱导依赖性潜能的作用机制；可采用多种动物行为学模型，如自身给药模型、药物辨别模型评价等，对镇痛药进行非临床依赖性评价研究。重点综述传统及新型镇痛药物依赖性的神经生物学、遗传学和表观遗传学方面的机制研究，概述非临床评价其依赖潜在性的研究方法，以期为镇痛药的安全性评价及临床用药提供参考依据。

Analgesics are a class of drugs that primarily act on the central nervous system (CNS) and selectively alleviate or eliminate pain and associated unpleasant emotions such as fear, tension, and anxiety. Due to the CNS activity and effect on μ opioid receptor,it's likely to pose a potential risk of dependence, has become an important problem in the field of global public health. As a multifactorial disease, genetic factors, neurological factors, epigenetic factors, gender factors, and environmental influence may all be the mechanisms of analgesic induced dependence potential; various animal behavioral models, such as self-administration models and drug discrimination model evaluations, can be used to conduct non-clinical dependence evaluation studies on analgesics. Above all, this article will focus on reviewing the mechanisms of potential dependence of traditional and new analgesics in neurobiology, genetics, and epigenetics. It will also outline the research methods for non-clinical evaluation of their dependence potential, in order to provide reference for the safety evaluation and clinical use of analgesics.