Anxiety Increases Acid-Induced Esophageal Hyperalgesia

Objective: Anxiety at the time of gastrointestinal injury or inflammation increases the risk of developing visceral hyperalgesia. Distal esophageal acidification induces hyperalgesia in the non-acid exposed proximal esophagus, due to the sensitization of spinal dorsal horn neurones. The objective was to determine whether anxiety influences acid-induced hyperalgesia. Methods: A total of 19 healthy volunteers (n = 12 females; age, 22-57 years; mean, 35.7 years) completed a 10-minute mood induction paradigm (anxiety or neutral) with autonomic monitoring (visit 1). On visits 2 and 3, pain thresholds to electrical stimulation, in milliamperes (mA), were determined in the proximal esophagus and foot (control) before and after a 30-minute infusion of 0.15 M of hydrochloric acid. During esophageal acid infusion, the subjects randomly received anxiety or neutral mood induction with autonomic monitoring, in a crossover design. Anxiety and pain ratings were recorded pre and post infusion. Results: Visit 1: Anxiety induction increased anxiety scores (p < .001), mean arterial pressure (p < .001), and cardiac sympathetic index (p = .007), and reduced parasympathetic measures (cardiac vagal tone [p = .05] and cardiac sensitivity to baroreflex [p = .006)]). Visit 2: Anxiety induction conferred greater acid-induced hyperalgesia compared with neutral (-4.9 mA versus 2.7 mA, p = .009, analysis of covariance). No differences in autonomic measures were found during acid infusion with anxiety or neutral mood induction. Conclusions: Anxiety induction increases acid-induced esophageal hyperalgesia; anxiety, thus, facilitates central sensitization in the esophagus. Our studies provide a new model for studying the effects of anxiety on esophageal hyperalgesia and may allow testing of therapeutic strategies to reduce this effect.