Effects of esophageal acidification on esophageal reflexes controlling the upper esophageal sphincter

Esophageal acid exposure can alter upper esophageal sphincter (UES) function, but the mechanism is unknown. The aim of this study was to determine the effects of esophageal acid exposure on esophago-UES relaxation (EURR) and contractile (EUCR) reflexes. Cats, decrebrate ( n = 27) or chronic ( n = 4), were implanted with electromyographic electrodes on pharynx, larynx, and esophagus. The esophagus was infused with either NaCl (0.9%) or HCl (0.1 N). The EUCR was activated by balloon distension in acute cats and slow air injection in chronic cats, and the EURR was activated by rapid air injection in both sets of cats. We found that NaCl infused for 15 or 30 min had no effect on EUCR or EURR in acute cats. HCl infused for 15, 30, or 45 min significantly ( P < 0.05) decreased the sensitivity to activate EUCR. HCl infused for 15 min significantly ( P < 0.05) increased and for 45 min significantly ( P < 0.05) decreased sensitivity to activate EURR. In chronic cats, HCl infused for 15 min/day increased sensitivity to activate EURR and decreased ( P < 0.05) sensitivity to activate EUCR after 4 days of infusion. EURR occurred spontaneously during HCl infusions on the 3rd and 4th ( P < 0.05) days of HCl infusion. We conclude that esophageal acid exposure initially sensitizes the esophagus to activation of EURR and desensitizes to activation of EUCR, but with longer exposure desensitizes to both. The alteration in sensitivity to activate EURR and EUCR caused by gastroesophageal reflux may play a role in the generation of supraesophageal reflux. NEW & NOTEWORTHY In acute studies, short-term esophageal acid exposure sensitizes esophagus to activation of esophago-upper esophageal sphincter relaxation response (EURR), whereas longer-term exposure inhibits EURR. Short- or long-term esophageal acid exposure decreases sensitivity to activation of esophago-upper esophageal sphincter contractile response (EUCR). In chronic studies, short-term esophageal acid exposure has the same effects on EURR and EUCR as occur acutely, but these effects take days to develop. Alteration in EURR and EUCR caused by gastroesophageal reflux may play a role in reflux disease.

Characterization and mechanisms of the pharyngeal swallow activated by stimulation of the esophagus

Stimulation of the esophagus activates the pharyngeal swallow response (EPSR) in human infants and animals. The aims of this study were to characterize the stimulus and response of the EPSR and to determine the function and mechanisms generating the EPSR. Studies were conducted in 46 decerebrate cats in which pharyngeal, laryngeal, and esophageal motility was monitored using EMG, strain gauges, or manometry. The esophagus was stimulated by balloon distension or luminal fluid infusion. We found that esophageal distension increased the chance of occurrence of the EPSR, but the delay was variable. The chance of occurrence of the EPSR was related to the position, magnitude, and length of the stimulus in the esophagus. The most effective stimulus was long, strong, and situated in the cervical esophagus. Acidification of the esophagus activated pharyngeal swallows and sensitized the receptors that activate the EPSR. The EPSR was blocked by local anesthesia applied to the esophageal lumen, and electrical stimulation of the recurrent laryngeal nerve caudal to the cricoid cartilage (RLNc) activated the pharyngeal swallow response. We conclude that the EPSR is activated in a probabilistic manner. The receptors mediating the EPSR are probably mucosal slowly adapting tension receptors. The sensory neural pathway includes the RLNc and superior laryngeal nerve. We hypothesize that, because the EPSR is observed in human infants and animals, but not human adults, activation of EPSR is related to the elevated position of the larynx. In this situation, the EPSR occurs rather than secondary peristalsis to prevent supraesophageal reflux when the esophageal bolus is in the proximal esophagus.

Translational aspects of rectal evoked potentials: A comparative study in rats and humans

BackgroundIn recent years only few novel drugs targeting visceral pain have been developed. This lack of success may be explained by animal models having poor predictive value. To increase the success of translating results from animals to humans there is a demand for comparable test models. The aim was to establish a comparable and reliable translational model to evoke mechanical rectal pain in rats and humans.MethodsMechanical rectal rapid balloon distension was done on two different days in 12 rats (separated by 24.3 ± 7.1 days) and 18 humans (separated by 9.3 ± 1.3 days). Evoked potentials were recorded from permanently implanted skull-electrodes in rats, at stimulation pressure of 80 mmHg and duration of 100 ms. In human surface electrodes and individualized pressure, corresponding to the pain detection threshold, lasting 150 ms, were used. Within- and between days reproducibility were assessed in terms of latencies, amplitudes and frequency content.ResultsIn both rats and humans evoked potentials with tri-phasic morphology were recorded. No differences in latencies, amplitudes and power distribution were seen within or between days (all F ≤ 2.0; all P ≥ 0.2). The analyses of the EPs revealed peak-to-peak amplitude as the most reproducible parameter within (ICC ≥ 0.84) and between (ICC ≥ 0.70) days, seen across both species. The spectral analyses showed that the EEG power was distributed mainly in the delta and theta bands. The main power in rats was contained in the theta band (45%), whereas humans had the predominant power in the delta band (46%).ConclusionA unique visceral translational platform was established to reliably assess neurophysiologic response to rapid balloon distension in rats and humans. The model provides an approach to study basic and clinical pain as well as pharmacological intervention.