title: Paeoniflorin exerts analgesic and hypnotic effects via adenosine A1 receptors in a mouse neuropathic pain model.
abstract: BACKGROUND
  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.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.|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.|Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Dou
authors.initials: D
authors.lastname: Yin
authors.affiliation: 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.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Tian-Xiao
authors.initials: TX
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Hu
authors.affiliation: 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.|Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Qu
authors.affiliation: Department of Neurology, School of Medicine, Boston University, Boston, MA, USA.
authors.forename: Jiang-Fan
authors.initials: JF
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China. nncheng@fudan.edu.cn.
authors.forename: Neng-Neng
authors.initials: NN
authors.lastname: Cheng
authors.affiliation: 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.|Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China. huangzl@fudan.edu.cn.
authors.forename: Zhi-Li
authors.initials: ZL
authors.lastname: Huang
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D005960:Glucosides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D039821:Monoterpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009437:Neuralgia / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011597:Psychomotor Performance / Q000187:drug effects; D043682:Receptor, Adenosine A1 / Q000187:drug effects* / Q000235:genetics; D012584:Sciatic Nerve / Q000473:pathology; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy; D006027:Glycosides
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D000700:Analgesics; D005960:Glucosides; D006993:Hypnotics and Sedatives; D039821:Monoterpenes; D018696:Neuroprotective Agents; D016760:Proto-Oncogene Proteins c-fos; D043682:Receptor, Adenosine A1; C015423:peoniflorin; D006027:Glycosides
keywords: C-Fos; Knockout mice; Sleep disturbance