Effect of Psycho-Pharmacological Modulation of the Autonomic Nervous System on Human Oesophageal Pain Hypersensitivity

Abstract

Background: Altered autonomic nervous system (ANS) function has been proposed as a mechanism in the development of central sensitisation (CS) and visceral pain hypersensitivity (VPH). The contribution of the parasympathetic nervous system (PNS) and the factors that mediate differences in sensitisation to acid are unclear and their study will clarify risk factors for oesophageal pain hypersensitivity (OPH) in gastrooesophageal reflux disease. Aims: To investigate psychophysiological and pharmacological manipulation of PNS tone in the development of OPH, and to determine factors which predict the development of OPH to acid infusion in healthy volunteers in a validated model of acid induced OPH. Methods: Pain thresholds to electrical stimulation in the proximal oesophagus were determined before and after a 30-minute distal oesophageal infusion of 0.15 mol/L hydrochloric acid in subjects. Sympathetic (SNS) and PNS parameters were measured at baseline and continuously thereafter. Subjects underwent psychological profiling for anxiety, depression, attachment vulnerability and personality type. Using this model, five studies were undertaken: Study 1 a pilot study to trail modulation suitability for further study used. In Study 2, subjects who demonstrated secondary hyperalgesia in the proximal non-acid-exposed oesophagus performed deep or sham breathing. Study 3 subjects, who did not sensitise to acid, underwent a validated stress test to induce OPH. With Study 4, deep breathing with IV saline (placebo) or atropine (PNS antagonist) was used to evaluate deep breathing’s induced PNS tone in OPH reduction. Study 5, a genetic pilot study, exploring the role of the GCH-1 haplotype in VPH. Results: ANS control’s key role in CS was clarified. Deep breathing increased PNS tone and prevented acid-induced OPH in comparison to sham breathing and confirmed increased PNS tone’s reversal of OPH. Psychological factors of anxiety, alexithymia and attachment status influence ANS modulation of CS. Individuals’ predisposition to VPH due to psychogenetic profiles were clarified and their biopsychosocial role illustrated. Conclusions and Inferences: A mechanistic explanation for the analgesic effect of deep breathing is provided with potential therapeutic implications in the treatment of VPH syndromes. Further clinical study is warranted to develop cost-effective treatments for chronic VPH syndromes.