title: Colon distention induces persistent visceral hypersensitivity by mechanotranscription of pain mediators in colonic smooth muscle cells.
abstract: Abdominal pain and distention are major complaints in irritable bowel syndrome. Abdominal distention is mainly attributed to intraluminal retention of gas or solid contents, which may cause mechanical stress to the gut wall. Visceral hypersensitivity (VHS) may account for abdominal pain. We sought to determine whether tonic colon distention causes persistent VHS and if so whether mechanical stress-induced expression (mechanotranscription) of pain mediators in colonic smooth muscle cells (SMCs) plays a role in VHS. Human colonic SMCs were isolated and stretched in vitro to investigate whether mechanical stress upregulates expression of the pain mediator cyclooxygenase-2 (COX-2). Rat colon was distended with a 5-cm-long balloon, and gene expression of COX-2, visceromotor response (VMR), and sensory neuron excitability were determined. Static stretch of colonic SMCs induced marked expression of COX-2 mRNA and protein in a force- and time-dependent manner. Subnoxious tonic distention of the distal colon at ∼30-40 mmHg for 20 or 40 min induced COX-2 expression and PGE2 production in colonic smooth muscle, but not in the mucosa layer. Lumen distention also increased VMR in a force- and time-dependent manner. The increase of VMR persisted for at least 3 days. Patch-clamp experiments showed that the excitability of colon projecting sensory neurons in the dorsal root ganglia was markedly augmented, 24 h after lumen distention. Administration of COX-2 inhibitor NS-398 partially but significantly attenuated distention-induced VHS. In conclusion, tonic lumen distention upregulates expression of COX-2 in colonic SMC, and COX-2 contributes to persistent VHS.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; and.
authors.forename: You-Min
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; and.
authors.forename: Chester C
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; and.
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Xu
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Li-Yen
authors.initials: LY
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; and xushi@utmb.edu.
authors.forename: Xuan-Zheng
authors.initials: XZ
authors.lastname: Shi
mesh_terms: D000200:Action Potentials; D000818:Animals; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000294:innervation / Q000378:metabolism / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006801:Humans; D008297:Male; D009119:Muscle Contraction; D009129:Muscle Tonus; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009578:Nitrobenzenes / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology; D013314:Stress, Mechanical; D013449:Sulfonamides / Q000494:pharmacology; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2
keywords: COX-2; irritable bowel syndrome; mechanical stress; visceral sensitivity