Abstract
Background: Sleep disturbance is common in patients with gastroesophageal reflux disease (GERD). Up-regulation of transient receptor potential vanilloid receptor-1 (TRPV-1) has been shown in esophageal mucosa of patients with GERD. We have shown that esophageal infusion of a TRPV-1 agonist, capsaicin-contained red pepper sauce, induced heartburn symptoms in healthy adults and patients with GERD (Gastroenterology 2014;146;S678). Aim: We aimed to test the hypothesis whether sleep dysfunction modulates capsaicin sensitization via the upregulation of the TRPV-1 receptor and whether there was any interaction between capsaicin sensitization and sleep dysfunction in GERD patients. Methods: We enrolled 22 patients with sleep disturbance and 18 patients without sleep disturbance based on the Pittsburg Sleep Quality Index (PSQI) with > 5 indicating sleep disturbance. All subjects had an infusion with capsaicin-contained red pepper sauce into the mid-esophagus. Esophageal sensation to capsaicin infusion was documented via measures of lag time to initial heartburn perception, heartburn intensity rating, and sensitivity score. Objective sleep measures were assessed by ambulatory actigraphy. Results: The patients with sleep disturbance had a shorter lag time to initial heartburn perception (p = 0.03) and a greater sensory intensity rating (p = 0.02). The sensitivity score for capsaicin infusion was greater in patients with sleep disturbance when compared with those without sleep disturbance (p = 0.04). Actigraphy measures revealed that patients with sleep disturbance also had poor sleep efficiency (p = 0.04) and longer awakening time (p = 0.03). The lag time for perceiving capsaicin infusion was positively correlated with total sleep time (r = 0.33, p = 0.03). Conclusions: We have shown that GERD patients with sleep dysfunction have significantly enhanced perception to capsaicin infusion as compared with those without sleep dysfunction. The positive correlation between capsaicin lag time and total sleep time suggests that poor sleep does create a visceral hyperalgesia most likely via an upregulation of the TRPV1 receptor. Our study supports the notion that there is a link between sleep disturbance and capsaicin sensitization in patients with GERD and identifying patients with sleep disturbance may optimize the treatment of GERD patients.
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