Long‐lasting visceral hypersensitivity in a model of DSS ‐induced colitis in rats

Background: Persistent visceral hypersensitivity is a key component of functional and inflammatory gastrointestinal diseases. Current animal models fail to fully reproduce the characteristics of visceral pain in humans, particularly as it relates to persistent hypersensitivity. This work explores the validity of DSS-induced colitis in rats as a model to mimic chronic intestinal hypersensitivity. Methods: Exposure to DSS (5% for 7 days) was used to induce colitis in rats. Thereafter, changes in viscerosensitivity (visceromotor responses to colorectal distension—CRD), the presence of somatic referred pain (mechanosensitivity of the hind paws, von Frey test) and the expression (qRT-PCR) of sensory-related markers (colon, lumbosacral DRGs, and lumbosacral spinal cord) were assessed at different times during the 35 days period after colitis induction. Results: Following colitis, a sustained increase in visceromotor responses to CRD were observed, indicative of the presence of visceral hypersensitivity. Responses in animals without colitis remained stable over time. In colitic animals, somatic referred hypersensitivity was also detected. DSS-induced colitis was associated to a differential expression of sensory-related markers (with both pro- and anti-nociceptive action) in the colon, lumbosacral DRGs and lumbosacral spinal cord; indicating the presence of peripheral and central sensitization. Conclusions and Inferences: DSS-induced colitis in rats is associated to the generation of a long-lasting state of visceral (colonic) hypersensitivity, despite clinical colitis resolution. This model reproduces the changes in intestinal sensitivity characteristics of inflammatory and functional gastrointestinal disorders in humans and can be used in the characterization of new pharmacological treatments against visceral pain.