Abstract
Background: There is a growing realization that the gut–brain axis signaling is critical for maintaining the health and homeostasis of the Central Nervous System (CNS) and the intestinal environment. The role of Short-Chain Fatty Acids (SCFAs), such as Sodium Propionate (SP) and Sodium Butyrate (SB), has been reported to counteract inflammation activation in the central and Enteric Nervous System (ENS). Methods: In this study, we evaluated the role of the SCFAs in regulating the pathophysiology of migraine and correlated dysregulations in the gut environment in a mouse model of Nitroglycerine (NTG)-induced migraine. Results: We showed that, following behavioral tests evaluating pain and photophobia, the SP and SB treatments attenuated pain attacks provoked by NTG. Moreover, treatments with both SCFAs reduced histological damage in the trigeminal nerve nucleus and decreased the expression of proinflammatory mediators. Ileum evaluation following NTG injection reported that SCFA treatments importantly restored intestinal mucosa alterations, as well as the release of neurotransmitters in the ENS. Conclusions: Taken together, these results provide evidence that SCFAs exert powerful effects, preventing inflammation through the gut–brain axis, suggesting a new insight into the potential application of SCFAs as novel supportive therapies for migraine and correlated intestinal alterations.
Highlights
Migraine is a severe and disabling brain condition characterized by recurrent episodes of headache [1]
The symptoms of migraine headache are intensified during exposure to light; migraine photophobia is experienced by nearly 90% of migraine sufferers with normal eyesight and depends on the photic signals from the eye that converge on trigeminal vascular neurons somewhere along their path [30]
We showed that NTG injection causes restlessness in mice, and contrarily, Short-Chain Fatty Acids (SCFAs)-treated mice with higher doses of 30 mg/kg and 100 mg/kg were less susceptible to light (Figure 1E)
Summary
Migraine is a severe and disabling brain condition characterized by recurrent episodes of headache [1]. Most of the studies aiming to investigate the roles of gut resident intestinal flora in neurological disorders usually use microbiota estimation, and delineating the immune cells and their inflammatory mediators release neurotransmitter role in the Enteric Nervous System (ENS) [9]. Methods: In this study, we evaluated the role of the SCFAs in regulating the pathophysiology of migraine and correlated dysregulations in the gut environment in a mouse model of Nitroglycerine (NTG)-induced migraine. Results: We showed that, following behavioral tests evaluating pain and photophobia, the SP and SB treatments attenuated pain attacks provoked by NTG. Treatments with both SCFAs reduced histological damage in the trigeminal nerve nucleus and decreased the expression of proinflammatory mediators.
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