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Immunol."],"published-print":{"date-parts":[[2026,10,23]]},"abstract":"<jats:p>\n                    Visceral pain in ulcerative colitis is conventionally attributed to inflammatory cascades, though whether immune cells directly transduce mechanical cues into nociceptive signals remains unclear. Here, we show that the mechanosensitive channel Piezo1 in tissue-resident CX3CR1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages directly drives colitis-associated visceral hypersensitivity. Piezo1 triggered calcium influx and nuclear factor \u03baB nuclear translocation that occupied the\n                    <jats:italic toggle=\"yes\">Ngf<\/jats:italic>\n                    promoter to induce nerve growth factor (NGF) synthesis. This macrophage-derived NGF remodeled and sensitized the peripheral terminals of TRPV1\n                    <jats:sup>+<\/jats:sup>\n                    nociceptive afferents in neuroimmune units. Using a minimally inflammatory intracolonic zymosan model, we found that this Piezo1-NGF-TrkA axis functions as a direct mechanosensory relay largely independent of cytokine cascades. Genetic deletion of\n                    <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">Ngf<\/jats:italic>\n                    in resident macrophages, or\n                    <jats:italic toggle=\"yes\">Ntrk1<\/jats:italic>\n                    in TRPV1\n                    <jats:sup>+<\/jats:sup>\n                    neurons, abolished visceral hyperalgesia in both inflammatory and noninflammatory models. These findings reveal tissue-resident macrophages as autonomous mechanical sensors that establish a direct, parallel pain transmission pathway to sensory nerves during disease.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.aeb3809","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T17:58:12Z","timestamp":1792778292000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["An autonomous macrophage-nociceptor mechanosensory relay drives chronic visceral pain"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1169-5426","authenticated-orcid":true,"given":"Liyan","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, China."},{"name":"University of Chinese Academy of Sciences, Beijing 100049, 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