Psychopharmacology (Berl). 2015 Oct 29. [Epub ahead of print]

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

Yin D1,2,3, Liu YY4, Wang TX2, Hu ZZ2, Qu WM2,5, Chen JF6, Cheng NN7, Huang ZL8,9.

• 1Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
• 2State 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.
• 3Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
• 4State 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.
• 5Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
• 6Department of Neurology, School of Medicine, Boston University, Boston, MA, USA.
• 7Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China. nncheng@fudan.edu.cn.
• 8State 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.
• 9Institutes 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.

KEYWORDS:

C-Fos; Knockout mice; Sleep disturbance

PMID:

26514553