Abstract EN:

Chronic pain is defined in terms of pain that persists more than 3 months or beyond the healing time of a given injured tissue. It affects 1.5 billion people worldwide. Because two-thirds of sufferers report a clear dissatisfaction with current treatment, it is critical to further investigate this matter. Here, we describe gene-environment interactions supporting pain chronification. We have demonstrated that the Myo1a gene is expressed in specific subset of sensory neurons and that male mice with a Myo1a deficiency develop a chronic mechanical hypersensitivity (hereafter called chronic pain), no matter the etiology of pain. Interestingly, we have shown that Myo1a KO males develop chronic pain only when produced under single genotype housing conditions (SGH) but not under mixed genotype housing conditions (MGH). Furthermore, crossing of Myo1a deficient mice from MGH produced a second generation of Myo1a KO males of SGH, which recapitulated the original chronic pain phenotype, thereby demonstrating that Myo1a-environment interactions are involved in pain chronification. Because Myo1a is strongly expressed in the gut where its loss of function (lof) has been associated to architectural defects, we asked whether such lof may be associated to a gut microbiota dysbiosis supporting pain chronification. We performed 16S rRNA sequencing and demonstrated that Myo1a KO males exhibit a gut microbiota dysbiosis under SGH but not MGH conditions. Moreover, our antibiotic prenatal treatment of Myo1a deficient mice allows them to recover from inflammatory pain. Our findings thus suggest that based on gene-gut microbiota interactions, it is now possible to propose à-la-carte analgesics.