title: Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice.
abstract: OBJECTIVE
  Gelsemine, an alkaloid from the Chinese herb Gelsemium elegans (Gardn & Champ) Benth., is effective in mitigating chronic pain in rats. In the present study we investigated whether the alkaloid improved sleep disturbance, the most common comorbid symptoms of chronic pain, in a mouse model of neuropathic pain.
  
  
  METHODS
  Mice were subjected to partial sciatic nerve ligation (PSNL). After the mice were injected with gelsemine or pregabalin (the positive control) intraperitoneally, mechanical allodynia and thermal hyperalgesia were assessed, and electroencephalogram (EEG)/electromyogram (EMG) recording was performed. Motor performance of the mice was assessed using rota-rod test. c-Fos expression in the brain was analyzed with immunohistochemical staining.
  
  
  RESULTS
  In PSNL mice, gelsemine (2 and 4 mg/kg) increased the mechanical threshold for 4 h and prolonged the thermal latencies for 3 h. Furthermore, gelsemine (4 mg/kg, administered at 6:30 AM) increased non-rapid eye movement (non-REM, NREM) sleep, decreased wakefulness, but did not affect REM sleep during the first 3 h in PSNL mice. Sleep architecture analysis showed that gelsemine decreased the mean duration of wakefulness and increased the total number of episodes of NREM sleep during the first 3 h after the dosing. Gelsemine (4 mg/kg) did not impair motor coordination in PSNL mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of the anterior cingulate cortex, and gelsemine (4 mg/kg) decreased c-Fos expression by 58%. Gelsemine (4 mg/kg, administered at either 6:30 AM or 8:30 PM) did not produce hypnotic effect in normal mice. Pregabalin produced similar antinociceptive and hypnotic effects, but impaired motor coordination in PSNL mice.
  
  
  CONCLUSIONS
  Gelsemine is an effective agent for treatment of both neuropathic pain and sleep disturbance in PSNL mice; anterior cingulate cortex might play a role in the hypnotic effects of gelsemine.
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.|Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Yu-er
authors.initials: YE
authors.lastname: Wu
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Ya-dong
authors.initials: YD
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Yan-jia
authors.initials: YJ
authors.lastname: Luo
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Tian-xiao
authors.initials: TX
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Hui-jing
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Shuo-nan
authors.initials: SN
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.|Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Wei-min
authors.initials: WM
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.|Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.|Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Zhi-li
authors.initials: ZL
authors.lastname: Huang
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D031450:Gelsemium / Q000737:chemistry; D006930:Hyperalgesia / Q000188:drug therapy*; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000188:drug therapy*; D012584:Sciatic Nerve / Q000601:surgery; D012890:Sleep / Q000187:drug effects; D012893:Sleep Wake Disorders / Q000188:drug therapy*
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D006993:Hypnotics and Sedatives; C063230:gelsemine