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The Lung Microbiome Modulates Pain-Like Behavior Via the Lung-Brain Axis in a Nitroglycerin-Induced Chronic Migraine
Biying Liu1, Chengya Huang1, Xin Li1
1Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
Abstract:
Chronic migraine is one of the most common pain disorders, characterized by significant disability and a lack of safe, long-term, and effective treatment options. Recent studies highlight the interaction between the lung microbiota and the central nervous system. In this study, a nitroglycerin (NTG)-induced chronic migraine model is constructed in male C57BL/6 mice to explore these interactions. Notable alterations are observed in the lung microbiota of migraine-afflicted mice. Notably, there is a marked decrease in Proteobacteria in the chronic migraine group, associated with short-chain fatty acids and 5-hydroxytryptamine (5-HT). After the intratracheal injection of neomycin, the diversity of the lung microbiota is altered, resulting in the relief of migraines. This effect is also observed in mice that receive neomycin-treated bronchoalveolar lavage fluid (BALF) transplantation, further demonstrating the role of lung microbiota in this process. The altered lung microbiota activate the pulmonary vagus nerve via the Brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) pathway in the lung, which projects to the central nucleus of the solitary tract (NTS) and the dorsal raphe nucleus (DRN). This activation, in turn, stimulates the 5-HT neurons in the DRN, resulting in increased serotonin levels that contribute to pain relief in the chronic migraine model.
Insights
Altering lung microbiota composition can alleviate chronic migraine. This study shows that changes in gut bacteria impact the brain, offering a new therapeutic target for migraine relief.
Area of Science:
- Microbiology
- Neuroscience
- Gastroenterology
Background:
- Chronic migraine is a disabling pain disorder with limited treatment options.
- Emerging research suggests a gut-brain axis involving the lung microbiota and central nervous system.
- Understanding these interactions may reveal novel therapeutic strategies for migraine.
Purpose of the Study:
- To investigate the role of lung microbiota in a mouse model of chronic migraine.
- To explore the mechanisms by which lung microbiota influence migraine pathophysiology.
- To assess the therapeutic potential of modulating lung microbiota for migraine relief.
Main Methods:
- A nitroglycerin (NTG)-induced chronic migraine model was established in male C57BL/6 mice.
- Lung microbiota composition was analyzed in migraine-afflicted mice.
- Interventions included intratracheal neomycin administration and bronchoalveolar lavage fluid (BALF) transplantation.
- Vagal nerve activation and neurotransmitter levels (serotonin) were assessed.
Main Results:
- Migraine-afflicted mice exhibited significant alterations in lung microbiota, including decreased Proteobacteria.
- Neomycin treatment altered lung microbiota diversity and led to migraine relief.
- Transplantation of neomycin-treated BALF also ameliorated migraine symptoms.
- Lung microbiota alterations activated the pulmonary vagus nerve via the Brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) pathway, influencing serotonin release.
Conclusions:
- Lung microbiota play a crucial role in the pathophysiology of chronic migraine.
- Modulating lung microbiota composition offers a promising therapeutic avenue for migraine treatment.
- The findings elucidate a novel lung-microbiota-brain axis involved in migraine pain modulation.
