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In the present study, we found that miRNA-let7b5p was downregulated in the spinal cord of IBS model rats induced by neonatal colorectal distension. Concurrently, microglia exhibited a shift toward a pro-inflammatory M1 phenotype and selectively engulfed inhibitory synapses, resulting in impaired GABAergic neuronal function and disruption of the excitatory\/inhibitory balance. Intrathecal administration of a miRNA-let7b5p agomir suppressed M1-type microglial activation in the spinal cord, reduced pro-inflammatory cytokine levels, and alleviated visceral hypersensitivity, whereas antagomir treatment induced visceral hypersensitivity in control rats. Mechanistically, MAP3K3 was identified as a direct target of miRNA-let7b5p, and its knockdown recapitulated the protective effects conferred by miRNA upregulation. Collectively, these findings demonstrate that miRNA-let7b5p attenuates IBS-associated visceral hypersensitivity by downregulating MAP3K3, thereby inhibiting spinal microglial activation and restoring GABAergic neuronal function. This study provides novel insights into the pathogenesis of IBS-related visceral hypersensitivity and highlights a potential therapeutic target for drug development.<\/jats:p>","DOI":"10.1177\/17448069261430202","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T18:12:43Z","timestamp":1773252763000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["miRNA-let7b5p alleviates visceral hypersensitivity by inhibiting the activation of spinal microglial in male IBS-like rats"],"prefix":"10.1177","volume":"22","author":[{"given":"Xianhe","family":"Wu","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Pain Research Institute, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 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