Fu-Fang-Li-Shao Pill alleviates neuroinflammation through blocking TLR4/MyD88/MAPKs pathway in chronic migraine rats

Abstract

Neuroinflammation is supposed to be a crucial factor in the pathophysiology of migraine, which is caused by intracranial vasodilation and the release of vasoactive peptides. Fu-Fang-Li-Shao Pill (FFLSP), a prescription composed of Tribulus terrestris, Radix Paeoniae Alba, Radix Puerariae, Radix Salviae Miltiorrhizae, White Chrysanthemum, Uncariae Ramulus Cum Uncis, Concha Margaritifera, Fructus Viticis, Angelica Dahurica and Mentha Haplocalyx Briq, is an effective proved recipe for migraine patients which is developed by Shanghai Xuhui District Central Hospital. However, the pharmacological mechanisms of FFLSP in relieving migraine are not well understood. This study aims to assess the therapeutic effect of FFLSP on chronic migraine and to elucidate the underlying mechanisms. In our study, through the repeated subcutaneous injection of nitroglycerin (NTG), an animal model of chronic migraine was established which showed migraine-like symptoms such as head pain, ear redness and irritability. Here, NTG-induced chronic migraine rats were used to evaluate the inhibitory effect of FFLSP on neuroinflammation by conducting behavioral tests and molecular biology analyses. We observed that FFLSP possesses an excellent ability to relieve chronic migraine. FFLSP treatment was able to inhibit vasodilation by decreasing c-Fos and CGRP expressions in dura mater and trigeminal ganglion. Moreover, headache alleviation of NTG-induced migraine rats was decided by the inhibition of neuroinflammatory responses through FFLSP’s interruptive effect on the TLR4/MyD88/MAPKs pathway. FFLSP should be attentively considered as a potential therapeutic agent for chronic migraine by blocking inflammatory signal pathway in dura mater and trigeminal ganglion.