Therapeutic Effect and Mechanism of Emodin on Migraine via Inhibition of TRPV4/p38 Signaling Pathway in a Nitroglycerin-Induced Rat Model

Abstract

Background: Migraine is known as a persistent neurological condition marked by recurring bouts of head pain and diverse neurological manifestations. Emodin exhibits a wide range of pharmacological activities, particularly its neuroprotective effects on neurodegenerative diseases. Emodin is capable to alleviate nitroglycerin (NTG)-induced migraine in rats. Furthermore, it has been witnessed that transient receptor potential vanilloid-4 (TRPV4)/p38 signaling pathway is involved in the development of migraine pathogenesis. Methods: Rats subjected to repetitive NTG administration were considered a model replicating clinical manifestations of migraine. Three different Emodin dosage groups (high, medium, and low) and control group were used to observe the effects of different doses on the behavior and other related indicators of migraine rats. Results: The results showed that high and medium doses of Emodin significantly delayed the appearance time of redness and scratching in the ears of rats, shortened their disappearance time, and increased the mechanical pain threshold of rats, indicating that Emodin can remarkably improve the behavior of migraine rats and increase their mechanical pain threshold. At the same time, high and medium doses of Emodin significantly increased the content of peripheral blood 5-hydroxytryptamine (5-HT) in migraine rats, indicating that Emodin can treat migraine headaches by increasing the peripheral blood 5-HT content. In addition, high and medium doses of Emodin can reduce the expression of TRPV4 protein and p38 mRNA in the trigeminal ganglion of migraine rats, indicating that Emodin can negatively regulate the expression and gene transcription of TRPV4/p38 signaling pathway-related proteins. Therefore, it inhibits neuroinflammation, reduces pain-induced sensitization, and exerts a therapeutic effect on migraine. Conclusions: Our findings demonstrate that Emodin is capable to mitigate headaches, which are associated symptoms in migraine-afflicted rats. This effect is likely attributed to the elevation of peripheral blood 5-HT content and the suppression of expression and gene transcription related to the TRPV4/p38 signaling pathway.