title: Tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord contributes to chronic visceral pain in rats.
abstract: The roles of spinal N-methyl-d-aspartic acid receptor 2B (NR2B) subunit in central sensitization of chronic visceral pain were investigated. A rat model with irritable bowel syndrome (IBS) was established by colorectal distention (CRD) on post-natal days 8-14. Responses of the external oblique muscle of the abdomen to CRD were measured to evaluate the sensitivity of visceral pain in rats. The sensitivity of visceral pain significantly increased in IBS-like rats. Expressions of spinal NR2B subunit and phosphorylated NR2B subunit significantly increased by 50-55% in IBS-like rats when compared with those in control rats. Ro 25-6981, a selective antagonist of NR2B subunit, has a dose-dependent anti-allodynic and anti-hyperalgesic effect without causing motor dysfunction in IBS-like rats. Furthermore, the activation mechanism of the spinal NR2B subunit in chronic visceral pain was also investigated. Spinal administration of genistein, a specific inhibitor of tyrosine kinases, also decreased the visceral pain hypersensitivity of IBS-like rats in a dose-dependent manner. In addition, the expression of phosphorylated NR2B subunit was decreased after spinal administration of Ro 25-6981 or genistein in IBS-like rats. In conclusion, tyrosine kinase activation-induced phosphorylation of NR2B subunit may play a crucial role in central sensitization of chronic visceral pain.
authors.affiliation: School of Foundational Medical sciences, Fujian Medical University, Fuzhou City, Fujian Province 350108, PR China; Department of Physiology and Pathophysiology, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Zhen, Minhou County, Fuzhou City, Fujian Province 350108, PR China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Luo
authors.affiliation: School of Foundational Medical sciences, Fujian Medical University, Fuzhou City, Fujian Province 350108, PR China; Department of Physiology and Pathophysiology, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Zhen, Minhou County, Fuzhou City, Fujian Province 350108, PR China.
authors.forename: Qin-Yan
authors.initials: QY
authors.lastname: Cai
authors.affiliation: School of Foundational Medical sciences, Fujian Medical University, Fuzhou City, Fujian Province 350108, PR China; Department of Physiology and Pathophysiology, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Zhen, Minhou County, Fuzhou City, Fujian Province 350108, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Foundational Medical sciences, Fujian Medical University, Fuzhou City, Fujian Province 350108, PR China; Department of Physiology and Pathophysiology, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Zhen, Minhou County, Fuzhou City, Fujian Province 350108, PR China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Guo
authors.affiliation: School of Foundational Medical sciences, Fujian Medical University, Fuzhou City, Fujian Province 350108, PR China; Department of Physiology and Pathophysiology, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Zhen, Minhou County, Fuzhou City, Fujian Province 350108, PR China.
authors.forename: Ai-Qin
authors.initials: AQ
authors.lastname: Chen
authors.affiliation: School of Foundational Medical sciences, Fujian Medical University, Fuzhou City, Fujian Province 350108, PR China.
authors.forename: Zhen-Quan
authors.initials: ZQ
authors.lastname: Wu
authors.affiliation: School of Foundational Medical sciences, Fujian Medical University, Fuzhou City, Fujian Province 350108, PR China; Department of Physiology and Pathophysiology, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Zhen, Minhou County, Fuzhou City, Fujian Province 350108, PR China. Electronic address: chunlin77550@126.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Lin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D019833:Genistein / Q000494:pharmacology; D043183:Irritable Bowel Syndrome / Q000150:complications; D008297:Male; D010147:Pain Measurement; D010636:Phenols / Q000627:therapeutic use; D010766:Phosphorylation / Q000502:physiology; D010880:Piperidines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism*; D059265:Visceral Pain / Q000209:etiology / Q000473:pathology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D014443:Tyrosine; D019833:Genistein
keywords: Chronic visceral pain; Genistein; N-methyl-d-aspartic acid receptor 2B subunit; Ro 25-6981; Spinal cord; Tyrosine kinase