Characterization of a reproducible gastric pain model using oral capsaicin titration in healthy volunteers

Background Sensory sensitization is one of the main pathophysiological hypotheses in functional gastrointestinal disorders (FGIDs). As sensitization may affect various sensory modalities, we aimed to develop a reproducible gastric pain model utilizing polymodal pathways for use in functional and other pain disorders. Methods In this double-blind, cross-over study 42 healthy subjects swallowed one capsule containing either capsaicin 0.5 mg or nocebo every 15 min until moderate pain (intensity > 30 on 100 mm visual analogue scale) was attained for at least 5 min. Pain was rated every minute. Capsaicin titration was repeated thrice for reliability calculation. Key Results Moderate pain in the upper abdomen was successfully achieved in 38 of 42 subjects (90%) with capsaicin titration and in one of 42 (2%) with nocebo. The median dosage required to induce moderate pain for at least 5 min was two capsules (interquartile range 1-3) and the median gastric pain intensity was 47 (41-53). The median duration of moderate pain was 8 min (5-12). Moderate pain was successfully reproduced with capsaicin in all subjects on study days 2 and 3, with an excellent Cronbach reliability coefficient of > 0.8. Conclusions & Inferences Standardized gastric pain can be conveniently achieved in a majority of healthy subjects using a simple oral capsaicin titration, with minimal adverse events. The between-test reproducibility is high and nocebo responses are negligible. This technique stimulating a multimodal physiological pathway will be useful in the investigation of sensory changes in FGIDs, including functional dyspepsia.