The Lung Microbiome Modulates Pain-Like Behavior Via the Lung-Brain Axis in a Nitroglycerin-Induced Chronic Migraine Mouse Model.

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.