Submitted on October 29, 2007
Accepted on February 5, 2008
Differential relaxation and contractile responses of the human upper esophageal sphincter mediated by interplay of mucosal and deep mechanoreceptor activation
Michal Marcin Szczesniak1, Sergio Enrique Fuentealba2, Anthea Burnett2, and Ian J. Cook3*
1 Department of Gastroenterology, St George Hospital, Kogarah, New South Wales, Australia; University of New South Wales, Sydney, New South Wales, Australia
2 Department of Gastroenterology, St George Hospital, Sydney, New South Wales, Australia
3 St. George Hospital, Australia; Department of Gastroenterology, St George Hospital, Sydney, New South Wales, Australia; University of New South Wales, Sydney, New South Wales, Australia
* To whom correspondence should be addressed. E-mail: i.cook{at}unsw.edu.au.
Background and aims: The neural mechanisms of distension induced esophago-UES reflexes have not been explored in humans. We investigated the modulation of these reflexes by mucosal anesthesia, acid exposure, and GABA-B receptor activation.
Methods: In 55 healthy human subjects, UES responses to rapid esophageal air insufflation and slow balloon distension were examined before and after pre-treatment with: 15ml of topical esophageal lignocaine; esophageal HCl infusion; baclofen 40mg p.o.
Results: In response to rapid esophageal distension, UES can variably relax or contract. Following mucosal blockade by topical lignocaine likelihood of a UES relaxation response was reduced by 11 % (p<0.01) and the likelihood of a UES contractile response was increased by 14% (p<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<0.05) following sensitization by prior mucosal acid exposure. The UES contractile response, elicited by balloon distension, was regionally dependent (p<0.05) (more frequent and of higher amplitude with proximal esophageal distension) and the response was attenuated by topical lignocaine (p<0.05). Baclofen (40mg.po.) had no effect on these UES reflexes.
Conclusion: Abrupt gaseous esophageal distension activates simultaneously both excitatory and inhibitory pathways to the UES. Partial blockade of the mucosal mechanosensistive 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.
