Mo1853 Prostaglandin E2 Mediates Acid-Induced Esophageal Sensation in Healthy Volunteers

Abstract

BACKGROUND Visceral hypersensitivity is frequent in IBS. Vandenberghe et al (Gut 2005) hypothesized that isolated sensitization of pain-specific (nociceptive) pathways would only increase the intensity of perceived painful sensations in hypersensitive patients, whereas sensitization of multimodal pathways would increase the perceived intensities of both painful and non-painful sensations. In hypersensitive patients with functional dyspepsia and IBS indirect evidence has been found favouring the latter mechanism. However, potentially important confounding factors such as somatization, anxiety and depression were not considered in previous studies. AIM To explore the impact of anxiety, depression and somatization in the analysis of sensitization of multimodal versus nociceptive afferent pathways in IBS patients with hypersensitivity. METHOD An ascending method of limits rectal distension protocol was performed in 138 patients with IBS according to Rome II criteria. After each distension the intensity of unpleasantness was reported on a visual analogue scale (VAS). Sensory thresholds for first sensation, urge to defecate, discomfort and pain were determined. The mean pain threshold -2 SD in healthy controls defined hypersensitivity in IBS. The anxiety, depression and somatization subscales of the SCL-90R were completed by all patients. RESULTS Sixty IBS patients (43.5%) were hypersensitive to rectal distension. There were no significant differences in sex, anxiety or depression between hyperand normosensitive patients, but hypersensitive patients were younger and reported higher levels of somatization (Table 1). The hypersensitive patients had lower sensory thresholds (first sensation 7±1 vs. 10±4 mmHg, urge to defecate 11±4 vs. 16±7 mmHg, discomfort 16±5 vs. 27±10 mmHg and pain 23±5 vs. 43±10 mmHg, all p<0.0001). The unpleasantness ratings at each distention step were higher in hypersensitive vs. normosensitive patients (Table 2). Somatization, depression and anxiety scores were then entered as covariates in separate repeated measures ANCOVAs, and the difference between hypersensitive and normosensitive patients in VAS ratings remained significant in all three models (partial eta squared (ηp2) 0.25-0.27; p<0.0001). Small independent effects on the unpleasantness ratings were noted for anxiety (ηp2 0.086; p=0.001) and depression (ηp2 0.068; p=0.004), but not for somatization (ηp2 0.025; p=0.09). CONCLUSIONS This study supports previous findings that multimodal afferent pathways and not only pain-specific pathways are implicated in the generation of visceral hypersensitivity in IBS. Somatization, anxiety or depression do not seem to explain the observed differences in perceived unpleasantness to non-painful rectal distensions in hypersensitive versus normosensitive IBS patients; the effect of anxiety and depression was independent of sensitivity. Descriptives