Intracolonic trinitrobenzene sulfonic acid (TNBS) post-inflammatory model of colonic hypersensitivity was worthy of being considered as the primary model for screening novel therapeutics for visceral pain of GI origin. • The model is relatively simple and can be used for high throughput studies. • The model has been characterized in rats and mice of both sexes. • The model has shown reliability and reproducibility in multiple laboratories. • The model has high construct validity and translational relevance (i.e., it has been used to predict outcomes in human clinical trials).

Other post-inflammatory models of colonic hypersensitivity can be produced with enemas of compounds such as acetic acid, capsaicin, mustard oil, or zymosan. Post-infective models using Trichinella spiralis or Campylobacter species have also been described. • Enemas are relatively simple to administer and can be used for high throughput studies. • There is only limited characterization (by sex or strain) for each source of inflammation. • The time-course to resolution of inflammation is variable for each model. • Less reproducibility across laboratories than the TNBS post-inflammatory model.

Stress-induced models of colonic hypersensitivity are most commonly produced through acute or chronic restraint stress, chronic variable stress, or water avoidance stress. • Stressor range from simple (restraint) to complex (variable stressors), which inversely correlates with overall throughput for drug screening. • The strain of the rodent will affect whether it habituates to homotypic stressors; may require the use of heterotypic stressors to produce colonic hypersensitivity. • Water avoidance stress (of different durations) is the most reproduced model.

Early life stress-induced models of colonic hypersensitivity include limited nesting, maternal separation, neonatal colonic irritation, and odor attachment learning. • Each model recapitulates different aspects of early life trauma but requires specific training to ensure reproducibility across laboratories. • Throughput is limited by litter size and the need to wait 70–90 days for rats to reach adulthood before testing compounds. • In most models, colonic hypersensitivity has only been demonstrated in male animals. • Some models require an additional stressor in adulthood to demonstrate colonic hypersensitivity.