• Y-J Zhao, J-H Li, B Hu, Y Wang, X-F Chang, R J Traub, and D-Y Cao.
• 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.
• Neurogastroenterol. Motil. 2018 Feb 1; 30 (2).

BackgroundWe 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-regulated kinase (ERK) in the spinal cord contributes to visceral hypersensitivity in this overlapping pain model.MethodsIn OVx with E2 replacement rats masseter muscle inflammation was followed by 3 day FS (comorbid condition). Depression-like 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-ERK1/2) in the L6-S2 dorsal spinal cord was analyzed by western blot.Key ResultsFS stress decreased sucrose consumption in E2 replaced rats in sucrose preference test. The expression of p-ERK1/2 in the L6-S2 dorsal spinal cord increased significantly in E2 with comorbid rats. Intrathecal injection of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor PD98059 blocked the visceral hypersensitivity induced by masseter muscle inflammation combined with FS stress.Conclusions & InferencesThese 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.© 2017 John Wiley & Sons Ltd.

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