title: Antinociceptive and hypnotic activities of pregabalin in a neuropathic pain-like model in mice.
abstract: To evaluate the antinociceptive and hypnotic effects of pregabalin, we established a neuropathic pain-like model in mice using partial sciatic nerve ligation (PSNL), and examined thermal hyperalgesia, mechanical allodynia, electroencephalogram, rota-rod testing, and c-Fos expression in the anterior cingulate cortex. Gabapentin was used as a reference drug in the study. Pregabalin administered i.g. at 12.5 and 25mg/kg prolonged the duration of thermal latencies by 1.4- and 1.6-fold and increased the mechanical threshold by 2.2- and 3.1-fold 3h after administration, respectively, but did not affect motor coordination in PSNL mice, compared with vehicle control. Pregabalin (12.5 and 25mg/kg) given at 6:30 increased the amount of non-rapid eye movement sleep in a 4-h period by 1.3- and 1.4-fold, respectively, in PSNL mice. However, pregabalin (25mg/kg) given at 20:30 did not alter the sleep pattern in normal mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of anterior cingulate cortex by 2.1-fold, which could be reversed by pregabalin. These results indicate that pregabalin is an effective treatment for both neuropathic pain and sleep disturbance in PSNL mice.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Department of Pharmacology, Wannan Medical College, Wuhu, China.
authors.forename: Tian-Xiao
authors.initials: TX
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Department of Pharmacology, College of Pharmaceutical Science, Fudan University, Shanghai, China.
authors.forename: Dou
authors.initials: D
authors.lastname: Yin
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Wannan Medical College, Wuhu, China.
authors.forename: Ya-Dong
authors.initials: YD
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Qu
authors.affiliation: Baker-Norton Pharmaceutical Co., Ltd, Kunming, China.
authors.forename: Wu-Jian
authors.initials: WJ
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Wannan Medical College, Wuhu, China. Electronic address: zyhongwnmc@aliyun.com.
authors.forename: Zong-Yuan
authors.initials: ZY
authors.lastname: Hong
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. Electronic address: huangzl@fudan.edu.cn.
authors.forename: Zhi-Li
authors.initials: ZL
authors.lastname: Huang
mesh_terms: D000588:Amines / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D000077206:Gabapentin; D016762:Genes, fos / Q000187:drug effects; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000523:psychology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D004856:Postural Balance / Q000187:drug effects; D000069583:Pregabalin / Q000494:pharmacology* / Q000627:therapeutic use*; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000523:psychology; D012893:Sleep Wake Disorders / Q000139:chemically induced / Q000523:psychology; D012895:Sleep, REM / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D006993:Hypnotics and Sedatives; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
keywords: Anterior cingulate cortex; Neuropathic pain; Pregabalin; Sleep disturbance; c-Fos