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

被引:44
|
作者
Yin, Dou [1 ,2 ,3 ]
Liu, Yuan-Yuan [2 ,3 ]
Wang, Tian-Xiao [2 ,3 ]
Hu, Zhen-Zhen [2 ,3 ]
Qu, Wei-Min [2 ,3 ,4 ,5 ]
Chen, Jiang-Fan [6 ]
Cheng, Neng-Neng [1 ]
Huang, Zhi-Li [2 ,3 ,4 ,5 ]
机构
[1] Fudan Univ, Dept Pharmacol, Sch Pharm, Shanghai 200433, Peoples R China
[2] Fudan Univ, Dept Pharmacol, State Key Lab Med Neurobiol, Sch Basic Med Sci, Shanghai 200433, Peoples R China
[3] Fudan Univ, Shanghai Key Lab Bioact Small Mol, Sch Basic Med Sci, Shanghai 200433, Peoples R China
[4] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China
[5] Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200433, Peoples R China
[6] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA
基金
中国国家自然科学基金;
关键词
C-Fos; Knockout mice; Sleep disturbance; EYE-MOVEMENT SLEEP; SCIATIC-NERVE LIGATION; BENZODIAZEPINE SITE; ANIMAL-MODELS; MICE LACKING; C-FOS; RAT; HYPERALGESIA; ACTIVATION; NEURONS;
D O I
10.1007/s00213-015-4108-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. The present study evaluated effects of paeoniflorin on neuropathic pain and associated insomnia and the mechanisms involved. 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. 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 A(1) receptor (R, A(1)R) 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 A(1)R knockout PSNL mice. Immunohistochemical study showed that paeoniflorin inhibited c-Fos overexpression induced by PSNL in the anterior cingulate cortex and ventrolateral periaqueductal gray. The present findings indicated that paeoniflorin exerted analgesic and hypnotic effects via adenosine A(1)Rs and might be of potential use in the treatment of neuropathic pain and associated insomnia.
引用
收藏
页码:281 / 293
页数:13
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