{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T03:17:02Z","timestamp":1777605422005,"version":"3.51.4"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T00:00:00Z","timestamp":1500595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671097"],"award-info":[{"award-number":["81671097"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2016JM3015"],"award-info":[{"award-number":["2016JM3015"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008510","name":"University of Maryland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We previously developed an animal model to examine mechanisms that underlie the emergence of visceral hypersensitivity modeling pain characteristics of temporomandibular disorder (TMD) patients with comorbid irritable bowel syndrome (IBS). In ovariectomized (OVx) rats with estradiol (E2) replacement, visceral hypersensitivity developed subsequent to masseter muscle inflammation followed by repeated forced swim (FS) stress. The purpose of this study was to investigate whether activation of extracellular signal\u2010regulated kinase (ERK) in the spinal cord contributes to visceral hypersensitivity in this overlapping pain model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In OVx with E2 replacement rats masseter muscle inflammation was followed by 3\u00a0day FS (comorbid condition). Depression\u2010like behaviors were assessed by sucrose preference and in the elevated plus maze, and visceral sensitivity was measured by the visceromotor response (VMR) to colorectal distention. The protein level of ERK1\/2 and phosphorylated ERK1\/2 (p\u2010ERK1\/2) in the L6\u2010S2 dorsal spinal cord was analyzed by western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>FS stress decreased sucrose consumption in E2 replaced rats in sucrose preference test. The expression of p\u2010ERK1\/2 in the L6\u2010S2 dorsal spinal cord increased significantly in E2 with comorbid rats. Intrathecal injection of mitogen\u2010activated protein kinase (MAPK) kinase (MEK) inhibitor PD98059 blocked the visceral hypersensitivity induced by masseter muscle inflammation combined with FS stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>These data indicate that ERK1\/2 activation contributes to the visceral hypersensitivity evoked by craniofacial inflammation pain combined with stress. The results may provide a new therapeutic avenue for alleviating overlapping pain conditions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13161","type":"journal-article","created":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T08:30:03Z","timestamp":1500625803000},"source":"Crossref","is-referenced-by-count":9,"title":["Extracellular signal\u2010regulated kinase activation in the spinal cord contributes to visceral hypersensitivity induced by craniofacial injury followed by stress"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6551-5863","authenticated-orcid":false,"given":"Y.\u2010J.","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research Research Center of Stomatology Xi'an Jiaotong University College of Stomatology  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.\u2010H.","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research Research Center of Stomatology Xi'an Jiaotong University College of Stomatology  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research Research Center of Stomatology Xi'an Jiaotong University College of Stomatology  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging the First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"X.\u2010F.","family":"Chang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research Research Center of Stomatology Xi'an Jiaotong University College of Stomatology  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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