{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:09:23Z","timestamp":1787497763411,"version":"build-2736575974"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"19","funder":[{"name":"National Health and Medical Research Council of Australia","award":["R.D Wright Biomedical Research Fellow (APP1126378 to S.M.B),NHMRC Australia Project Grants (#1083480,#1139366"],"award-info":[{"award-number":["R.D Wright Biomedical Research Fellow (APP1126378 to S.M.B),NHMRC Australia Project Grants (#1083480,#1139366"]}]},{"name":"National Health and Medical Research Council of Australia","award":["#1140297 to S.M.B)"],"award-info":[{"award-number":["#1140297 to S.M.B)"]}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["Discovery Early Career Research Award (DE130100223 to A.M.H)"],"award-info":[{"award-number":["Discovery Early Career Research Award (DE130100223 to A.M.H)"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["Discovery Project (DP180101395 to A.M.H"],"award-info":[{"award-number":["Discovery Project (DP180101395 to A.M.H"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["S.M.B)."],"award-info":[{"award-number":["S.M.B)."]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"name":"DFG","award":["grant FOR 2060 (FE 438\/5-2"],"award-info":[{"award-number":["grant FOR 2060 (FE 438\/5-2"]}]},{"name":"DFG","award":["FE 438\/6-2 to R.F),the Fund for Science (to R.F"],"award-info":[{"award-number":["FE 438\/6-2 to R.F),the Fund for Science (to R.F"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10,4]]},"abstract":"<jats:p>Irritable bowel syndrome (IBS) patients suffer from chronic abdominal pain and extraintestinal comorbidities, including overactive bladder (OAB) and interstitial cystitis\/painful bladder syndrome (IC-PBS). Mechanistic understanding of the cause and time course of these comorbid symptoms is lacking, as are clinical treatments. Here, we report that colitis triggers hypersensitivity of colonic afferents, neuroplasticity of spinal cord circuits, and chronic abdominal pain, which persists after inflammation. Subsequently, and in the absence of bladder pathology, colonic hypersensitivity induces persistent hypersensitivity of bladder afferent pathways, resulting in bladder-voiding dysfunction, indicative of OAB\/IC-PBS. Daily administration of linaclotide, a guanylate cyclase-C (GC-C) agonist that is restricted to and acts within the gastrointestinal tract, reverses colonic afferent hypersensitivity, reverses neuroplasticity-induced alterations in spinal circuitry, and alleviates chronic abdominal pain in mice. Intriguingly, daily linaclotide administration also reverses persistent bladder afferent hypersensitivity to mechanical and chemical stimuli and restores normal bladder voiding. Linaclotide itself does not inhibit bladder afferents, rather normalization of bladder function by daily linaclotide treatment occurs via indirect inhibition of bladder afferents via reduced nociceptive signaling from the colon. These data support the concepts that cross-organ sensitization underlies the development and maintenance of visceral comorbidities, while pharmaceutical treatments that inhibit colonic afferents may also improve urological symptoms through common sensory pathways.<\/jats:p>","DOI":"10.1172\/jci.insight.121841","type":"journal-article","created":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T11:01:24Z","timestamp":1538564484000},"source":"Crossref","is-referenced-by-count":78,"title":["Chronic linaclotide treatment reduces colitis-induced neuroplasticity and reverses persistent bladder dysfunction"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3900-7141","authenticated-orcid":true,"given":"Luke","family":"Grundy","sequence":"first","affiliation":[{"name":"Visceral Pain Research Group, Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia."},{"name":"Centre for Nutrition and 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