Chronic colitis-induced visceral pain is associated with increased anxiety during quiescent phase

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2019-06, Vol.316 (6), p.G692-G700
• Main Authors: Salameh, Emmeline, Meleine, Mathieu, Gourcerol, Guillaume, do Rego, Jean-Claude, do Rego, Jean-Luc, Legrand, Romain, Breton, Jonathan, Aziz, Moutaz, Guérin, Charlène, Coëffier, Moïse, Savoye, Guillaume, Marion-Letellier, Rachel
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Anxiety; Anxiety - etiology; Anxiety - physiopathology; Behavior, Animal - physiology; Capsaicin receptors; Colitis; Colitis - immunology; Colitis - physiopathology; Colitis - psychology; Colon; Colon - innervation; Colon - metabolism; Colon - physiopathology; Complications; Cytokines - analysis; Disease Models, Animal; Distension; Dorsal root ganglia; Fibrosis; Gastrointestinal Motility; Hypersensitivity; Inflammation - immunology; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - physiopathology; Inflammatory Bowel Diseases - psychology; Injection; Interleukin 10; Interleukin 6; Intestine; Life Sciences; Male; Neurons and Cognition; Open-field behavior; Pain; Permeability; Peroxidase; Peroxidase - analysis; Rats; Remission; Rodents; Sulfonic acid; Tight Junction Proteins - analysis; Transient receptor potential proteins; Tumor necrosis factor-α; Visceral Pain - etiology; Visceral Pain - immunology; Visceral Pain - physiopathology; Visceral Pain - psychology
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00248.2018

Inflammatory bowel diseases (IBD) are characterized by repetition of flares and remission periods leading to chronic postinflammatory sequelae. Among postinflammatory sequelae, one-third of patients with IBD are suffering from functional symptoms or psychological comorbidities that persist during remission. The aim of our study was to assess functional and behavioral sequelae of chronic colitis in rats with quiescent intestinal inflammation. Chronic colitis was induced by a weekly intrarectal injection of increasing concentrations of trinitrobenzene sulfonic acid (TNBS) for 3 wk (15-45 mg of TNBS) in 30 rats, whereas the control rats ( = 24) received the vehicle. At 50 days post-TNBS, visceral sensitivity was assessed by visceromotor response to colorectal distension, and transient receptor potential vanilloid type 1 (TRPV1) expression was also quantified in the colon and dorsal root ganglia. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein, myeloperoxidase activity, histological score, and cytokine production (IL-6, IL-10, and TNF-α). Anxiety behavioral tests were performed from 50 to 64 days after the last TNBS injection. Chronic TNBS induced ) a visceral hypersensitivity ( = 0.03), ) an increased colon weight-to-length ratio ( = 0.01), ) higher inflammatory and fibrosis scores ( = 0.0390 and = 0.0016, respectively), and ) a higher colonic IL-6 and IL-10 production ( = 0.008 and = 0.005, respectively) compared with control rats. Intestinal permeability, colonic production of TNF-α, myeloperoxidase activity, and TRPV1 expression did not differ among groups. Chronic TNBS increased anxiety-related behavior in the open-field test and in the acoustic stress test. In conclusion, chronic colitis induced functional sequelae such as visceral hypersensitivity and increased anxiety with a low-grade intestinal inflammation. Development of a representative animal model will allow defining novel therapeutic approaches to achieve a better management of IBD-related sequelae. Patients with inflammatory bowel diseases have impaired quality of life. Therapeutic progress to control mucosal inflammation provides us an opportunity to develop novel approaches to understand mechanisms behind postinflammatory sequelae. We used a chronic colitis model to study long-term sequelae on visceral pain, gut barrier function, and psychological impact. Chronic colitis induced functional symptoms and increased anxiety in t