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Activation of central orexin signaling has been shown to ameliorate these gastrointestinal disturbances via vagal pathways mediated by brain orexin and central muscarinic receptors. Given that several studies suggest that L\u2010carnitine, a naturally occurring amino acid, can activate orexin signaling, we hypothesized that L\u2010carnitine attenuates these gastrointestinal abnormalities in a rat model of IBS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Visceral pain thresholds to colonic balloon distension were evaluated by electromyographic recordings of abdominal muscle contractions. Colonic permeability was assessed by measuring Evans blue uptake in lipopolysaccharide (LPS) and corticotropin\u2010releasing factor (CRF) \u2010induced IBS models in male Sprague\u2013Dawley rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Intragastric administration of L\u2010carnitine (3\u2013200\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u2009day\n                      <jats:sup>\u22121<\/jats:sup>\n                      for 3\u2009days) dose\u2010dependently prevented LPS\u2010induced visceral hypersensitivity and colonic hyperpermeability, and attenuated these changes induced by CRF. Intracisternal administration of SB\u2010334867, an orexin 1 receptor antagonist, abolished the effects of L\u2010carnitine in the LPS model. Moreover, atropine, sulpiride, a dopamine D\n                      <jats:sub>2<\/jats:sub>\n                      receptor antagonist, and N\n                      <jats:sup>G<\/jats:sup>\n                      \u2010nitro\u2010L\u2010arginine methyl ester, a nitric oxide synthesis inhibitor, but not scopolamine butylbromide, a peripheral muscarinic receptor antagonist, blocked the effects of L\u2010carnitine. Additionally, compound C, an AMPK inhibitor, and GW9662, a PPAR\u2010\u03b3 antagonist, also abolished L\u2010carnitine's effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Inferences<\/jats:title>\n                    <jats:p>\n                      L\u2010Carnitine prevents visceral hypersensitivity and colonic hyperpermeability in IBS models via mechanisms involving brain orexin, as well as central muscarinic, dopamine D\n                      <jats:sub>2<\/jats:sub>\n                      , nitric oxide, AMPK, and PPAR\u2010\u03b3 signaling. These findings suggest that L\u2010carnitine may represent a promising therapeutic option for IBS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70389","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T13:54:58Z","timestamp":1782914098000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["L\u2010Carnitine Improves Visceral Hypersensitivity and Colonic Hyperpermeability in a Rat Model of Irritable Bowel Syndrome"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4225-2575","authenticated-orcid":false,"given":"Tsukasa","family":"Nozu","sequence":"first","affiliation":[{"name":"Department of Regional Medicine and Education Asahikawa Medical University  Asahikawa Hokkaido Japan"},{"name":"Center for Medical Education Asahikawa Medical University  Asahikawa Hokkaido Japan"},{"name":"Department of General Medicine Asahikawa Medical University  Asahikawa Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Miyagishi","sequence":"additional","affiliation":[{"name":"Department of General Medicine Asahikawa Medical University  Asahikawa Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatomo","family":"Ishioh","sequence":"additional","affiliation":[{"name":"Department of General Medicine Asahikawa Medical University  Asahikawa Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Takakusaki","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Physiology Asahikawa Medical University  Asahikawa Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1810-007X","authenticated-orcid":false,"given":"Toshikatsu","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of General Medicine Asahikawa Medical University  Asahikawa Hokkaido 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