Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2015-01, Vol.308 (1), p.R18-R27
• Main Authors: Chen, Jinghong, Winston, John H, Fu, Yu, Guptarak, Jutatip, Jensen, Kathryn L, Shi, Xuan-Zheng, Green, Thomas A, Sarna, Sushil K
• Format: Article
• Language: English
• Subjects: Abdominal Pain - drug therapy; Abdominal Pain - etiology; Abdominal Pain - metabolism; Abdominal Pain - physiopathology; Abdominal Pain - psychology; Action Potentials; Anesthetics, Local - pharmacology; Animals; Anxiety; Anxiety - etiology; Anxiety - metabolism; Anxiety - physiopathology; Anxiety - prevention & control; Anxiety - psychology; Behavior, Animal; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - complications; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - physiopathology; Colitis, Ulcerative - psychology; Colon - innervation; Conditioning (Psychology); Depression - etiology; Depression - metabolism; Depression - physiopathology; Depression - prevention & control; Depression - psychology; Dextran Sulfate; Disease Models, Animal; Diterpenes - pharmacology; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; Ganglia, Spinal - physiopathology; Inflammatory bowel disease; Kv1.1 Potassium Channel - genetics; Kv1.1 Potassium Channel - metabolism; Kv1.4 Potassium Channel - genetics; Kv1.4 Potassium Channel - metabolism; Lidocaine - pharmacology; Mental disorders; Neural Control; Neurons; Rats; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Rodents; Time Factors; TRPV Cation Channels - agonists; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00298.2014

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.