Wuzhuyu Decoction relieves hyperalgesia by regulating central and peripheral 5-HT in chronic migraine model rats

作者：Nan Nan, Muxin Gong, Qi Wang, Mei-jing Li, Rui Xu, Zhe Ma, Sihui Wang, Hui Zhao, Yongsong Xu · 发表于：Phytomedicine · 年份：2021 · DOI：10.1016/j.phymed.2021.153905 · 被引用次数：27 · 研究领域：Migraine and Headache Studies、Urinary Bladder and Prostate Research、Nitric Oxide and Endothelin Effects

BACKGROUND: Chronic migraine (CM) is a highly disabling and burdensome disease. Wuzhuyu decoction (WZYD), a clinical used formula to treat and prevent episodic migraine and CM, has been reported to relieve the hyperalgesia of CM and increase brainstem and blood serotonin (5-hydroxytryptamine, 5-HT) in migraine model rats in previous studies; yet the mechanism is unclear. PURPOSE: This study aimed to observe the hyperalgesia relief effect of WZYD and investigate the mechanistic association with the regulation on central and peripheral 5-HT. METHODS: WZYD with different doses (3.372, 1.686 and 0.843 g/kg∙d) and the positive drug - sumatriptan (5.83 mg/kg∙3 d) were intragastrically administered in inflammatory soup (IS)-induced CM model rats, respectively. Hyperalgesia was assessed by facial mechanical withdrawal threshold and tail-flick latency. 5-HT was determined by ELISA. Western blot analysis, immunohistochemistry and immunofluorescence determination, and 16S rRNA gene sequencing were performed. RESULTS: WZYD significantly relieved the hyperalgesia by elevating the facial mechanical withdrawal threshold and tail-flick latency. In WZYD groups, increased 5-HT and decreased calcitonin gene-related peptide in both the brainstem and plasma, downregulated TNF-α, IL-1β, and c-fos expression in the brainstem were observed in dose-dependent manner. Interestingly, 5-HT in colon tissues were also observed, which is associated with upregulating tryptophan hydroxylase, serotonin transpo...