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Paeoniflorin exerts analgesic and hypnotic effects via adenosine A1 receptors in a mouse neuropathic pain model

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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.

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Acknowledgments

This study was supported in part by grants-in-aid for scientific research from the National Basic Research Program of China (2011CB711000, 2015CB856401, 2009ZX09303-006), the National Natural Science Foundation of China (81420108015, 81301135, 31171010, 31171049, 31121061, 31271164, J1210041, 31471064), a key laboratory program of the Education Commission of Shanghai Municipality (ZDSYS14005), the Shanghai Committee of Science and Technology (13ZR1403200, 14JC1400900, 13dz2260700, 13140903100), and the Shanghai Leading Academic Discipline Project (B119).

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  1. Dou Yin

    Present address: Department of Neurology, Rui** Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China

    Dou Yin & Neng-Neng Cheng

  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

    Dou Yin, Yuan-Yuan Liu, Tian-**ao Wang, Zhen-Zhen Hu, Wei-Min Qu & Zhi-Li Huang

  3. Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China

    Wei-Min Qu & Zhi-Li Huang

  4. Department of Neurology, School of Medicine, Boston University, Boston, MA, USA

    Jiang-Fan Chen

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Yin, D., Liu, YY., Wang, TX. et al. Paeoniflorin exerts analgesic and hypnotic effects via adenosine A1 receptors in a mouse neuropathic pain model. Psychopharmacology 233, 281–293 (2016). https://doi.org/10.1007/s00213-015-4108-6

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