{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:26:45Z","timestamp":1790404005561,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T00:00:00Z","timestamp":1589328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Forest Research Institute"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Linaclotide, a guanylate cyclase C agonist relieves irritable bowel syndrome with predominant constipation (IBS\u2010C) symptoms, but how it improves pain in humans is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the effects of linaclotide and placebo on the afferent and efferent gut\u2010brain\u2010gut signalling in IBS\u2010C patients, in a randomised clinical trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with IBS\u2010C (Rome III) and rectal hypersensitivity were randomised (2:1) to receive linaclotide (290\u00a0\u00b5g) or placebo for 10\u00a0weeks and undergo bi\u2010directional gut and brain axis assessment using anorectal electrical stimulations and transcranial\/transspinal\u2010anorectal magnetic stimulations. Rectal sensations were examined by balloon distention. Assessments included abdominal pain, bowel symptoms and quality of life (QOL) scores. Primary outcomes were latencies of recto\u2010cortical and cortico\u2010rectal evoked potentials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010nine patients participated; 26 received linaclotide and 13 received placebo. Rectal cortical evoked potentials latencies (milliseconds) were significantly prolonged with linaclotide compared to baseline (P1:\u0394 19\u00a0\u00b1\u00a06, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.005; N1:\u0394 20\u00a0\u00b1\u00a07, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.02) but not with placebo (P1:\u0394 3\u00a0\u00b1\u00a05; N1:\u0394 4.7\u00a0\u00b1\u00a05,<jats:italic>P<\/jats:italic>\u00a0=\u00a00.3) or between groups. The efferent cortico\u2010anorectal and spino\u2010anorectal latencies were unchanged. The maximum tolerable rectal volume (cc) increased significantly with linaclotide compared to baseline (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and placebo (\u0394 29\u00a0\u00b1\u00a010 vs 4\u00a0\u00b1\u00a020, (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.03). Abdominal pain decreased (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) with linaclotide but not between groups. Complete spontaneous bowel movement frequency increased (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), and IBS\u2010QOL scores improved (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01) with linaclotide compared to baseline and placebo. There was no difference in overall responders between linaclotide and placebo (54% vs 23%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.13).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Linaclotide prolongs afferent gut\u2010brain signalling from baseline but both afferent and efferent signalling were unaffected compared to placebo. Linaclotide significantly improves rectal hypersensitivity, IBS\u2010C symptoms and QOL compared to placebo. These mechanisms may explain the effects of linaclotide on pain relief in IBS\u2010C patients.<\/jats:p><jats:p>ClinicalTrials.Gov: Registered at Clinical trials.gov no NCT02078323.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15772","type":"journal-article","created":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T02:38:35Z","timestamp":1589423915000},"page":"1332-1341","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Randomised clinical trial: linaclotide vs placebo\u2014a study of bi\u2010directional gut and brain axis"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4446-8452","authenticated-orcid":false,"given":"Satish S.C.","family":"Rao","sequence":"first","affiliation":[{"name":"Division of Neurogastroenterology\/Motility Medical College of Georgia Augusta University Augusta GA 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