鎮(zhèn)痛藥是一類主要作用于中樞神經(jīng)系統(tǒng)（CNS），能選擇性地緩解或消除疼痛及伴隨的不愉快情緒（如恐懼、緊張、焦慮等）的藥物。由于鎮(zhèn)痛藥的CNS活性和對μ阿片受體的作用，存在依賴性潛在風(fēng)險(xiǎn)，已成為全球性公共衛(wèi)生領(lǐng)域的重要問題。作為多成因的疾病，遺傳學(xué)因素、神經(jīng)系統(tǒng)因素、表觀遺傳因素、性別因素和環(huán)境差異都可能是鎮(zhèn)痛藥誘導(dǎo)依賴性潛能的作用機(jī)制；可采用多種動(dòng)物行為學(xué)模型，如自身給藥模型、藥物辨別模型評價(jià)等，對鎮(zhèn)痛藥進(jìn)行非臨床依賴性評價(jià)研究。重點(diǎn)綜述傳統(tǒng)及新型鎮(zhèn)痛藥物依賴性的神經(jīng)生物學(xué)、遺傳學(xué)和表觀遺傳學(xué)方面的機(jī)制研究，概述非臨床評價(jià)其依賴潛在性的研究方法，以期為鎮(zhèn)痛藥的安全性評價(jià)及臨床用藥提供參考依據(jù)。

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.