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In the Methods, we discussed why, based on experimental and clinical studies, we chose 80% as the increase in average activation of GCL and GPX by estradiol

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Mechanistically, TRPV1-lineage nociceptors exhibit mechanosensitivity through stretch-activated Piezo2 channels, which drive visceral afferent firing and pain responses to colorectal distension under both physiological and pathological conditions, including IBS-like states 107

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Methods: We used an integrative multi-omics approach in a mouse model of DCI