Differential relaxation and contractile responses of the human upper esophageal sphincter mediated by interplay of mucosal and deep mechanoreceptor activation

Abstract

Szczesniak MM, Fuentealba SE, Burnett A, Cook IJ. Differential relaxation and contractile responses of the human upper esophageal sphincter mediated by interplay of mucosal and deep mechanoreceptor activation. Am J Physiol Gastrointest Liver Physiol 294: G982-G988, 2008. First published February 7, 2008 doi:10.1152/ajpgi.00496.2007.-Background and aims: the neural mechanisms of distension-induced esophagoupper esophageal sphincter (UES) reflexes have not been explored in humans. We investigated the modulation of these reflexes by mucosal anesthesia, acid exposure, and GABAB receptor activation. In 55 healthy human subjects, UES responses to rapid esophageal air insufflation and slow balloon distension were examined before and after pretreatment with 15 ml of topical esophageal lidocaine, esophageal HCl infusion, and baclofen 40 mg given orally. In response to rapid esophageal distension, UES can variably relax or contract. Following a mucosal blockade by topical lidocaine, the likelihood of a UES relaxation response was reduced by 11% (P Ͻ 0.01) and the likelihood of a UES contractile response was increased by 14% (P Ͻ 0.001) without alteration in the overall UES response rate. The UES contractile response to rapid esophageal air insufflation was also increased by 8% (P Ͻ 0.05) following sensitization by prior mucosal acid exposure. The UES contractile response, elicited by balloon distension, was regionally dependent (P Ͻ 0.05) (more frequent and of higher amplitude with proximal esophageal distension), and the response was attenuated by topical lidocaine (P Ͻ 0.05). Baclofen (40 mg po) had no effect on these UES reflexes. Abrupt gaseous esophageal distension activates simultaneously both excitatory and inhibitory pathways to the UES. Partial blockade of the mucosal mechanosensitive receptors permits an enhanced UES contractile response mediated by deeper esophageal mechanoreceptors. Activation of acid-sensitive esophageal mucosal chemoreceptors upregulates the UES contractile response, suggestive of a protective mechanism. esophagus; lidocaine; HCl IMPROVED KNOWLEDGE of the neuropharmacology of reflexive responses of the upper esophageal sphincter (UES) and esophagoesophageal reflexes (secondary peristalsis) is relevant to the understanding of the pathophysiology of conditions characterized by impaired esophageal clearance, an abnormal belch reflex, and excessive esophagopharyngeal regurgitation. These conditions are potentially important in the pathogenesis of extraesophageal disorders such as reflux laryngitis, cough, and asthma.Several reflexive UES responses triggered by stimulation of sensory afferents proximally from the pharynx (14) and distally from the esophagus (1, 5) have been demonstrated. The esophago-UES reflexes are mediated via the brain stem by vagal afferents arising from esophageal mucosa and from muscle layers (11). The efferent targets of these reflexes are the component muscles of the UES and selected muscle groups that exert a distracting force on the hyoid bones (22). Physiological stu...

Response of the Upper Esophageal Sphincter to Esophageal Distension Is Affected by Posture, Velocity, Volume, and Composition of the Infusate

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