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Sleep disturbance is closely associated with chronic pain.Given the bidirectional relationship between pain and sleep, treatment must focus on alleviation of both the pain and sleep disturbance.Paeoniflorin, a main active compound of the total glucosides of paeony,has been well documented to exhibit neuroprotective effects.In this study, we prepared a mouse model of neuropathic pain by partial ligation of sciatic nerve in mice and investigated the analgesic and hypnotic effects of paeoniflorin.We also examined whether adenosine A1 receptors (A1Rs) involved in the analgesic and hypnotic activities of paeoniflorin.Finally, c-Fos expression in the brain was analyzed by immunohistochemistry.The results showed that intraperitoneally administration of paeoniflorin at 50,100 mg· kg-1 significantly increased the mechanical threshold and prolonged the thermal latency in partial sciatic nerve ligation (PSL) mice.Treatment with paeoniflorin at 50, 100 mg· kg-1 increased non-rapid eye movement (non-REM, NREM) sleep by 38% and 58%, and concomitantly decreased wakefulness by 36% and 52% during the 2 h after administration, respectively.However, pretreatment with 8-cyclopentyl-1,3-dimethylxanthine (CPT),a specific adenosine A1R antagonist, abolished the analgesic and hypnotic effects of paeoniflorin.Moreover, there was no significant difference in mechanical threshold, thermal latency and NREM sleep amount after the administration of paeoniflorin at 100 mg· kg-1 in A1 R KO PSL mice.The elevated level of c-Fos expression in the cingulate cortex and PAG induced by PSL was remarkably inhibited by paeoniflorin.These results indicate that paeoniflorin exerts analgesic and hypnotic effects via adenosine A1 Rs in a mouse neuropathic pain model.