title: Evaluation of analgesic, sedative effects and antimigraine mechanism of Qilong Toutong Granule () in rodents.
abstract: OBJECTIVE
  To evaluate the analgesic and sedative effects of Qilong Toutong Granule (, QTG) and explore its possible mechanisms.
  
  
  METHODS
  Kunming mice were randomly divided into 6 groups: normal control group, Zhengtian Pill (, ZTP) group, Western medicine group, and high-dose (5.2 g/kg), medium-dose (2.6 g/kg) and low-dose (1.3 g/kg) of QTG groups. After completing the prophylactic treatment for 3 days, hot-plate test and acetic acid-induced writhing test were used to assess the analgesic effect, and spontaneous locomotor test and sodium pentobarbital-induced hypnosis activity were adopted to estimate the sedative effect. Sprague-Dawley rats were grouped into normal control group, model group, ZTP group, rizatriptan group, and high-dose (3.6 g/kg), medium-dose (1.8 g/kg), and low-dose (0.9 g/kg) of QTG groups. After gavage for continuous 7 days, rats were intraperitoneally injected nitroglycerin, and 4 h later, blood samples were collected from postcava for measuring the levels of plasma calcitonin gene-related peptide (CGRP) and beta-endorphin (β-EP) by radioimmunoassay. Subsequently, rats were perfused transcardially and the brain tissues containing the trigeminal nucleus caudalis (TNC) were achieved for detecting the number of Fos-immunoreactive cells by immunohistochemical method.
  
  
  RESULTS
  In the mice experiments, compared with the normal control group, high- and medium-dose of QTG groups significantly raised the pain threshold (P<0.01), reduced the number of writhing response (P<0.01) and spontaneous activity (P<0.01), but had no influence on the sleeping rate of mice (P>0.05), and low-dose of QTG group also raised the pain threshold at 120 min (P=0.007), as well as lowered locomotor activity of mice at 2 h (P=0.003). On the study of migraine model rats, high- and medium-dose of QTG groups remarkably down-regulated the levels of plasma CGRP (P<0.01), up-regulated the levels of plasma β-EP (P<0.01) and inhibited the expression of Fos protein in TNC (P<0.01), compared with the model group.
  
  
  CONCLUSIONS
  QTG has obvious analgesic and sedative action and its mechanism on relieving migraine may be through regulating the levels of neurotransmitters and/or neuropeptides, and inhibiting the activation of Fos pathway.
authors.affiliation: Department of Encephalopathy, The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Wu
authors.forename: Mei-Kui
authors.initials: MK
authors.lastname: Zhang
authors.forename: Huai
authors.initials: H
authors.lastname: Huang