Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice  

作　　者：Yu-er WU Ya-dong LI Yan-jia LUO Tian-xiao WANG Hui-jing WANG Shuo-nan CHEN Wei-min QU Zhi-li HUANG 

机构地区：[1]State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China [2]Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China [3]Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China

出　　处：《Acta Pharmacologica Sinica》2015年第11期1308-1317,共10页中国药理学报（英文版）

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

摘　　要：Aim： 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. Conclusion： 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.Aim： 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. Conclusion： 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.

关 键 词：anterior cingulate cortex C-FOS ELECTROENCEPHALOGRAM gelsemine Gelsemium neuropathic pain PREGABALIN sleep disturbance 

分 类 号：S858.267.1[农业科学—临床兽医学] TS218[农业科学—兽医学]