SCFA Treatment Alleviates Pathological Signs of Migraine and Related Intestinal Alterations in a Mouse Model of NTG-Induced Migraine

Cells. 2021 Oct 14;10(10):2756. doi: 10.3390/cells10102756.

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.

Keywords: central nervous system; enteric nervous system; migraine; short-chain fatty acids; sodium butyrate; sodium propionate.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cytokines / metabolism
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Fatty Acids, Volatile / administration & dosage
  • Fatty Acids, Volatile / pharmacology
  • Fatty Acids, Volatile / therapeutic use*
  • Female
  • Gene Expression Regulation / drug effects
  • Hyperalgesia / chemically induced
  • Hyperalgesia / complications
  • Hyperalgesia / drug therapy
  • Inflammation Mediators / metabolism
  • Intestines / drug effects
  • Intestines / pathology*
  • Mice
  • Migraine Disorders / chemically induced*
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / genetics
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / complications
  • Nerve Degeneration / drug therapy
  • Nerve Growth Factors / metabolism
  • Neurons / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type I / metabolism
  • Nitroglycerin / administration & dosage
  • Pain / chemically induced
  • Pain / complications
  • Pain / drug therapy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Trigeminal Nuclei / pathology

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Fatty Acids, Volatile
  • Inflammation Mediators
  • Nerve Growth Factors
  • RNA, Messenger
  • Nitric Oxide
  • Nitric Oxide Synthase Type I
  • Nitroglycerin