Dezocine Exerts Analgesic Effects in Chronic Pain by Activation of κ- and μ-Opioid Receptors and Inhibition of Norepinephrine and Serotonin Reuptake.

Abstract

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.