Differential relaxation and contractile responses of the human upper esophageal sphincter mediated by interplay of mucosal and deep mechanoreceptor activation.
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 GABA(B) 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 < 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 lidocaine (P < 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.
Szczesniak
Michal M
MM
Dept. of Gastroenterology, St. George Hospital, Gray St., Kogarah, NSW, 2217 Australia.
Fuentealba
Sergio E
SE
Burnett
Anthea
A
Cook
Ian J
IJ
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage; D001418:Baclofen / Q000008:administration & dosage; D002404:Catheterization; D002628:Chemoreceptor Cells / Q000378:metabolism; D049631:Esophageal Sphincter, Upper / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage; D006801:Humans; D006851:Hydrochloric Acid / Q000008:administration & dosage; D007263:Infusions, Parenteral; D007327:Insufflation; D008012:Lidocaine / Q000008:administration & dosage; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010528:Peristalsis; D011312:Pressure; D012018:Reflex / Q000187:drug effects
D000779:Anesthetics, Local; D018755:GABA Agonists; D008012:Lidocaine; D001418:Baclofen; D006851:Hydrochloric Acid