Gut microbiota promotes pain chronicity in Myosin1A deficient male mice

Reynders, A.; Jhumka, A.; Gaillard, S.; Hoeffel, G.; Mantilleri, A.; Malapert, P.; Salio, C.; Ugolini, S.; Castets, F.; Saurin, A. J.; Serino, M.; Moqrich, A.

doi:10.1101/2023.02.21.529352

bioRxiv · 10.1101/2023.02.21.529352

Gut microbiota promotes pain chronicity in Myosin1A deficient male mice

Reynders, A.·Jhumka, A.·Gaillard, S.·Hoeffel, G.·Mantilleri, A.·Malapert, P.·Salio, C.·Ugolini, S.·Castets, F.·Saurin, A. J.·Serino, M.·Moqrich, A.

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Abstract

Over the past decade, the gut microbiota has emerged as an important regulator of nervous systems health and disease states1. Yet, its contribution to the pathogenesis of chronic somatic pain remains poorly documented. Chronic pain is a heavily debilitating disease affecting more than 1.5 billion people worldwide that can manifest through a long-lasting hypersensitivity to mechanical and/or thermal stimulations2,3. Maladaptive responses of dorsal root ganglia (DRG) neurons and spinal cord (SC) interneurons to tissue injuries and also of non-neuronal cells including DRG macrophages and SC microglia are acknowledged as important drivers of sensory symptoms underlying chronic pain4,3,5-7. Recent evidence shows that signals from gut microbiota are required for the initiation of injury-induced sensory hypersensitivity, via the ability to interact with the immune system8-11. However, whether and how gut microbiota promotes pain chronicity remains unknown. Here, we report that male mice lacking Myosin1a (KO)12 raised under single genotype housing conditions (KO-SGH) are predisposed to develop chronic injury-induced mechanical pain. We demonstrate that this predisposition is caused by their dysbiotic gut microbiota, which sustains the immune response in the DRG following neuropathic injury. Parental antibiotic treatment modifies gut microbiota composition and completely rescues the injury-induced chronic pain and associated DRG inflammatory response in male KO-SGH offspring. Together, our data establish a causal relationship between a dysbiotic gut microbiota and the predisposition to injury-induced chronic pain.

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Reynders, A., Jhumka, A., Gaillard, S., Hoeffel, G., Mantilleri, A., Malapert, P., Salio, C., Ugolini, S., Castets, F., Saurin, A. J., Serino, M., Moqrich, A.. 2023-02-21. Gut microbiota promotes pain chronicity in Myosin1A deficient male mice. https://doi.org/10.1101/2023.02.21.529352

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