Dou Yin1,2,3, Yuan-Yuan Liu4, Tian-Xiao Wang2, Zhen-Zhen Hu2, Wei-Min Qu2,5, Jiang-Fan Chen6, Neng-Neng Cheng7, Zhi-Li Huang8,9. 1. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China. 2. State Key Laboratory of Medical Neurobiology, Department of Pharmacology, and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China. 3. Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 4. State Key Laboratory of Medical Neurobiology, Department of Pharmacology, and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China. liuyy@shmu.edu.cn. 5. Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China. 6. Department of Neurology, School of Medicine, Boston University, Boston, MA, USA. 7. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China. nncheng@fudan.edu.cn. 8. State Key Laboratory of Medical Neurobiology, Department of Pharmacology, and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China. huangzl@fudan.edu.cn. 9. Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China. huangzl@fudan.edu.cn.
Abstract
RATIONAL: Neuropathic pain is frequently comorbid with sleep disturbances. Paeoniflorin, a main active compound of total glucosides of paeony, has been well documented to exhibit neuroprotective bioactivity. OBJECTIVE: The present study evaluated effects of paeoniflorin on neuropathic pain and associated insomnia and the mechanisms involved. METHODS: The analgesic and hypnotic effects of paeoniflorin were measured by mechanical threshold and thermal latency, electroencephalogram (EEG) and electromyogram, and c-Fos expression in a neuropathic pain insomnia model. RESULTS: The data revealed that paeoniflorin (50 or 100 mg/kg, i.p.) significantly increased the mechanical threshold and prolonged the thermal latency in partial sciatic nerve ligation (PSNL) mice. Meanwhile, paeoniflorin increased non-rapid eye movement (NREM) sleep amount and concomitantly decreased wakefulness time. However, pretreatment with l,3-dimethy-8-cyclopenthylxanthine, an adenosine A1 receptor (R, A1R) antagonist, abolished the analgesic and hypnotic effects of paeoniflorin. Moreover, paeoniflorin at 100 mg/kg failed to change mechanical threshold and thermal latency and NREM sleep in A1R knockout PSNL mice. Immunohistochemical study showed that paeoniflorin inhibited c-Fos overexpression induced by PSNL in the anterior cingulate cortex and ventrolateral periaqueductal gray. CONCLUSIONS: The present findings indicated that paeoniflorin exerted analgesic and hypnotic effects via adenosine A1Rs and might be of potential use in the treatment of neuropathic pain and associated insomnia.
RATIONAL: Neuropathic pain is frequently comorbid with sleep disturbances. Paeoniflorin, a main active compound of total glucosides of paeony, has been well documented to exhibit neuroprotective bioactivity. OBJECTIVE: The present study evaluated effects of paeoniflorin on neuropathic pain and associated insomnia and the mechanisms involved. METHODS: The analgesic and hypnotic effects of paeoniflorin were measured by mechanical threshold and thermal latency, electroencephalogram (EEG) and electromyogram, and c-Fos expression in a neuropathic pain insomnia model. RESULTS: The data revealed that paeoniflorin (50 or 100 mg/kg, i.p.) significantly increased the mechanical threshold and prolonged the thermal latency in partial sciatic nerve ligation (PSNL) mice. Meanwhile, paeoniflorin increased non-rapid eye movement (NREM) sleep amount and concomitantly decreased wakefulness time. However, pretreatment with l,3-dimethy-8-cyclopenthylxanthine, an adenosine A1 receptor (R, A1R) antagonist, abolished the analgesic and hypnotic effects of paeoniflorin. Moreover, paeoniflorin at 100 mg/kg failed to change mechanical threshold and thermal latency and NREM sleep in A1R knockout PSNL mice. Immunohistochemical study showed that paeoniflorin inhibited c-Fos overexpression induced by PSNL in the anterior cingulate cortex and ventrolateral periaqueductal gray. CONCLUSIONS: The present findings indicated that paeoniflorin exerted analgesic and hypnotic effects via adenosine A1Rs and might be of potential use in the treatment of neuropathic pain and associated insomnia.
Authors: Bertil B Fredholm; Adriaan P IJzerman; Kenneth A Jacobson; Joel Linden; Christa E Müller Journal: Pharmacol Rev Date: 2011-02-08 Impact factor: 25.468
Authors: Priscila L Santos; Renan G Brito; João Pedro S C F Matos; Jullyana S S Quintans; Lucindo J Quintans-Júnior Journal: Mol Neurobiol Date: 2017-07-10 Impact factor: 5.590
Authors: Feng Jiao; Kevin Varghese; Shaoxun Wang; Yedan Liu; Hongwei Yu; George W Booz; Richard J Roman; Ruen Liu; Fan Fan Journal: J Cardiovasc Pharmacol Date: 2021-06-01 Impact factor: 3.271