Related Experiment Video
Updated: Oct 17, 2025
Author Spotlight: Deciphering Electrical Networks Behind Complex Brain Activities and Disorders
Published on: November 1, 2024
The gut microbiome modulates nitroglycerin-induced migraine-related hyperalgesia in mice
Li Kang1,2, Wenjing Tang2, Yaofen Zhang3
1School of Medicine, Nankai University, Tianjin, China.
Background:
Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia.
Methods:
Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control.
Results:
In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-α concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-α in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control.
Conclusion:
Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine.
Insights
The gut microbiome plays a role in migraine pathogenesis. Altering gut microbiota in mice affected their pain sensitivity, with migraine patients' microbiota worsening pain.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- Gut microbiota disturbance is increasingly implicated in migraine pathogenesis.
- Existing evidence linking gut microbiome to migraine remains largely unsubstantiated.
Purpose of the Study:
- To investigate the influence of the gut microbiome on migraine-related hyperalgesia.
- To determine if gut microbiota composition affects pain sensitivity in a migraine model.
Main Methods:
- Evaluated nitroglycerin-induced hyperalgesia in mice with varied gut microbiota statuses (SPF, germ-free, antibiotic-treated, and germ-free colonized).
- Compared hyperalgesia in mice receiving microbiota from migraine patients versus healthy controls.
Main Results:
- Germ-free and antibiotic-treated mice showed altered basal sensitivity but no significant nitroglycerin-induced hyperalgesia.
- Colonizing germ-free mice with specific microbiota (GFC) restored hyperalgesia.
- Microbiota from migraine patients induced more severe hyperalgesia than microbiota from healthy controls.
Conclusions:
- The gut microbiome is involved in normal mechanical pain sensation.
- Gut microbiota composition significantly influences the pathogenesis of migraine.
