title: Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation.
abstract: Psychological disorders are prevalent in patients with inflammatory bowel disease; the underlying mechanisms remain unknown. We tested the hypothesis that ulcerative colitis-like inflammation induced by dextran sodium sulfate (DSS) exacerbates the ongoing spontaneous activity in colon-projecting afferent neurons that induces abdominal discomfort and anxiety, and depressive-like behaviors in rats. In this study, we used the conditioned place preference and standard tests for anxiety- and depression-like behaviors. DSS rats developed anxiety- and depression-like behaviors 10 to 20 days after the start of inflammation. Single-fiber recordings showed an increase in the frequency of spontaneous activity in L6-S1 dorsal root ganglion (DRG) roots. Prolonged desensitization of transient receptor potential vanilloid 1 (TRPV1)-expressing colonic afferents by resiniferatoxin (RTX) suppressed the spontaneous activity, as well as the anxiety- and depressive-like behaviors. Reduction in spontaneous activity in colon afferents by intracolonic administration of lidocaine produced robust conditioned place preference (CPP) in DSS rats, but not in control rats. Patch-clamp studies demonstrated a significant decrease in the resting membrane potential, lower rheobase, and sensitization of colon-projecting L6-S1 DRG neurons to generate trains of action potentials in response to current injection in DSS rats. DSS inflammation upregulated the mRNA levels of transient receptor potential ankyrin 1 and TRPV1 channels and downregulated that of Kv1.1 and Kv1.4 channels. Ulcerative colitis-like inflammation in rats induces anxiety- and depression-like behaviors, as well as ongoing abdominal discomfort by exacerbating the spontaneous activity in the colon-projecting afferent neurons. Alterations in the expression of voltage- and ligand-gated channels are associated with the induction of mood disorders following colon inflammation.
authors.affiliation: Enteric Neuromuscular Disorders and Visceral Pain Center, Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Texas;
authors.forename: Jinghong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Enteric Neuromuscular Disorders and Visceral Pain Center, Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Texas;
authors.forename: John H
authors.initials: JH
authors.lastname: Winston
authors.affiliation: Enteric Neuromuscular Disorders and Visceral Pain Center, Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Texas;
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Enteric Neuromuscular Disorders and Visceral Pain Center, Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Texas;
authors.forename: Jutatip
authors.initials: J
authors.lastname: Guptarak
authors.affiliation: Enteric Neuromuscular Disorders and Visceral Pain Center, Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Texas;
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Jensen
authors.affiliation: Enteric Neuromuscular Disorders and Visceral Pain Center, Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Texas;
authors.forename: Xuan-Zheng
authors.initials: XZ
authors.lastname: Shi
authors.affiliation: Department of Pharmacology and Toxicology, Center for Addiction Research, The University of Texas Medical Branch at Galveston, Texas.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Green
authors.affiliation: Enteric Neuromuscular Disorders and Visceral Pain Center, Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Texas; Department of Neuroscience and Cell Biology, The University of Texas Medical Branch at Galveston, Texas; and sksarna@utmb.edu.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Sarna
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D000200:Action Potentials; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control / Q000523:psychology; D001522:Behavior, Animal; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D003106:Colon / Q000294:innervation*; D003213:Conditioning, Psychological; D003863:Depression / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control / Q000523:psychology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000378:metabolism; D051665:Kv1.4 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D004224:Diterpenes; C489293:Kcna1 protein, rat; C496979:Kcna4 protein, rat; D051665:Kv1.4 Potassium Channel; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D051662:Kv1.1 Potassium Channel; D016264:Dextran Sulfate; D008012:Lidocaine; C024353:resiniferatoxin
keywords: anxiety; depression; inflammatory bowel disease; spontaneous activity in visceral afferent neurons; visceral hypersensitivity