Background: Dezocine is a leading analgesic in China used for relieving moderate to severe pain. Previous studies have characterized its pharmacological properties, demonstrating its role as a partial agonist at both the κ-opioid receptor (KOR) and the μ-opioid receptor (MOR), thereby producing potent antinociceptive effects in acute pain models. However, its efficacy and mechanisms in chronic pain management remained unclear. Methods: Chronic pain models, including chronic neuropathic pain and cancer pain, were employed using chronic constriction injury (CCI) of the sciatic nerve and bone cancer pain (BCP) methodologies, respectively. The assessment of the mechanical allodynia was conducted using a von Frey filament. Results: Dezocine, administered via the intraperitoneal route, alleviated both neuropathic pain and cancer pain in a dose-dependent manner, with ED₅₀ of 1.3 mg/kg and 1.6 mg/kg, respectively. In the CCI model, the analgesic effect of dezocine was significantly inhibited by pretreating with KOR antagonist nor-BNI, MOR antagonist β-FNA, α2-adrenoceptor antagonist yohimbine, and 5-HT2A receptor antagonist altanserin. In the BCP model, dezocine-induced analgesia was markedly suppressed by nor-BNI, β-FNA, and yohimbine but not altanserin. Conclusion: These results suggest that, in neuropathic pain, the analgesic effects of dezocine are mediated through KOR and MOR activation, together with norepinephrine reuptake inhibition (NRI) and serotonin reuptake inhibition. In contrast, in cancer pain, KOR and MOR activation and NRI are involved in mediating the analgesic effect of dezocine. This study, along with previous data, enhances our understanding of the potential clinical utility of dezocine and elucidates its mechanisms of action in chronic pain management.

Keywords: analgesic; chronic pain; dezocine; norepinephrine reuptake; opioid receptor; serotonin reuptake.

Copyright © 2025 Zihan Liu et al. Pain Research and Management published by John Wiley & Sons Ltd.

背景： 地佐辛是中国常用的镇痛药物，用于缓解中到重度疼痛。先前的研究已经描述了其药理特性，证明它在κ-阿片受体（KOR）和μ-阿片受体（MOR）上均为部分激动剂，从而在急性疼痛模型中产生强大的抗痛觉效应。然而，其在慢性疼痛管理中的有效性和机制仍不清楚。方法： 使用坐骨神经慢性结扎损伤（CCI）法建立慢性神经病理性疼痛模型，使用骨癌疼痛（BCP）模型来研究癌症引起的慢性疼痛。机械性触诱发痛的评估采用von Frey细丝进行。结果： 地佐辛通过腹腔注射给药，在剂量依赖的方式下减轻了神经病理性疼痛和癌症疼痛，ED₅₀分别为1.3 mg/kg 和 1.6 mg/kg。在CCI模型中，地佐辛的镇痛作用被KOR拮抗剂nor-BNI、MOR拮抗剂β-FNA、α2-肾上腺素受体拮抗剂育亨宾和5-HT2A受体拮抗剂奥坦西林预先处理显著抑制。在BCP模型中，地佐辛诱导的镇痛作用被nor-BNI、β-FNA 和 育亨宾但不是奥坦西林明显抑制。结论： 这些结果表明，在神经病理性疼痛中，地佐辛的镇痛效果是通过KOR和MOR激活，以及去甲肾上腺素再摄取抑制（NRI）和血清素再摄取抑制共同介导。相反，在癌症引起的慢性疼痛中，KOR和MOR激活及NRI参与了地佐辛镇痛作用的中介。这项研究结合以往的数据，增强了我们对地佐辛潜在临床应用的理解，并阐明其在慢性疼痛管理中的作用机制。

关键词： 镇痛剂；慢性疼痛；地佐辛；去甲肾上腺素再摄取抑制；阿片受体；血清素再摄取

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