Evaluation of analgesic, sedative effects and antimigraine mechanism of Qilong Toutong Granule () in rodents.

Abstract

To evaluate the analgesic and sedative effects of Qilong Toutong Granule (, QTG) and explore its possible mechanisms. 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. 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. 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.