Medical College of Wisconsin Dysphagia Institute, Division of Gastroenterology and Hepatology, and Departments of Medicine, Radiology, and Otolaryngology and Communicative Disorders, Medical College of Wisconsin and Veterans Affairs Medical Center, Milwaukee, Wisconsin 53226
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Preliminary human studies suggest the presence of an upper esophageal sphincter (UES) contractile reflex triggered by pharyngeal water stimulation. The purposes of this study were to further characterize this reflex and determine the threshold volume for its activation. We studied 10 healthy young volunteers by manometric technique before and after topical pharyngeal anesthesia. UES pressure responses to various volumes and temperatures of water injected into the pharynx were elucidated. At a threshold volume, rapid-pulse and slow continuous pharyngeal water injection resulted in significant augmentation of UES pressure in all volunteers. Threshold volume for inducing UES contraction averaged 0.1 ± 0.01 ml for rapid-pulse injection and was significantly smaller than that for slow continuous injection (1.0 ± 0.2 ml). UES pressure increase duration averaged 16 ± 4 s. Augmentation of UES resting tone by injection of water with three different temperatures was similar. This augmentation was abolished after topical anesthesia. Conclusions were that stimulation of the human pharynx by injection of minute amounts of water results in a significant increase in resting UES pressure: the pharyngo-UES contractile reflex. The magnitude of pressure increase due to activation of this reflex is not volume or temperature dependent. Loss of pharyngeal sensation abolishes this reflex.
upper esophageal sphincter; airway protection
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
DURING EARLIER STUDIES aimed at determining the threshold volume for triggering a pharyngeal/reflexive swallow (6), it was noted that subthreshold volumes for triggering a pharyngeal swallow resulted in augmentation of upper esophageal sphincter (UES) resting pressure. Subsequent works in a feline model (3) confirmed the presence of a contractile reflex triggered by pharyngeal mechanical stimulation that resulted in contraction of the cricopharyngeus muscle. However, the presence of this contractile reflex in humans and the threshold volume for its triggering have not been systematically studied. For this reason, the present study was undertaken to further characterize this reflex in young healthy humans.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Ten healthy volunteers, aged 33 ± 2 yr (range: 22-39 yr; 3 women, 7 men) were studied. The study was approved by the Human Research Review Committee of the Medical College of Wisconsin, and subjects gave informed consent before the study began. Each subject was studied before as well as after application of 4% Aquase xylocaine (Roxane Laboratory, Columbus, OH) to the pharynx, applied by a spraying device. Topical anesthesia was confirmed by abolition of the gag reflex.
A UES sleeve catheter (Dentsleeve, Adelaide, Australia) that incorporated a sleeve device (6 × 0.5 × 0.3 cm) and side-hole manometric ports at its proximal and distal ends for manometric positioning was used to monitor the UES resting pressure and its response to pharyngeal water stimulation. The sleeve assembly also had additional recording sites 4.5 cm distal and 3 cm proximal to the sleeve. After application of 2% xylocaine to the more patent nostril, the manometric assembly was introduced through the nose and positioned within the UES such that the manometric port immediately proximal to the sleeve was positioned 2 cm above the UES high-pressure zone. After manometric positioning, this port was used only for water injection and, similar to the other pharyngeal ports, was otherwise not perfused.
The nonperfused injection port, the esophageal tips, and the sleeve sensor were connected to pressure transducers in line with a pneumohydraulic pump (Arndorfer Medical Specialties, Greendale, WI). With this arrangement, the onset and offset of water injection and UES pressure were recorded on chart paper run at a speed of 25 mm/s, providing an equivalent of 40 ms for each millimeter distance of pen movement.
For pharyngeal stimulation, two modes of fluid delivery into the pharynx were tested: rapid-pulse and slow continuous injection. For pulse injection, we started with 0.05 ml, followed by 0.1 ml of water, and then increased the volume by 0.1-ml increments until an irrepressible swallow occurred. Slow continuous infusion was performed at a rate of 5.5 ml/min by using a Harvard infusion pump (model N0975; Harvard Apparatus, Dover, MA) until an irrepressible swallow occurred. Each injection was started immediately after the UES pressure returned to baseline after a swallow, and subjects withheld swallowing as long as they could. For both rapid and slow injection, liquid temperatures of 0, 37, and 60°C were tested with subjects in the supine position. Swallowing was monitored by submental surface electromyograph and the distinctive UES relaxation response during swallowing.
After the sleeve was positioned, each subject was monitored for 10 min for adaptation, and we then determined in each subject the consistent change in UES pressure in response to various volumes of pharyngeal water injection (3 of 3 injections). For comparison of UES pressure before the injection with that after the injection, the average end-expiratory pressure for a 10-s period before the injection was used. We measured the maximum UES pressure after pharyngeal water injection, excluding the 3-s interval before deglutitive relaxation, if a swallow occurred. This was done to avoid the commonly seen pressure increase that is registered by the sleeve during the orad excursion of the UES immediately before its swallow-induced relaxation. Also determined in each subject was the smallest volume that consistently triggered a pharyngeal swallow on rapid-pulse injection as well as on slow continuous injection.
Statistical analysis was performed by using one-way or two-way analysis of variance as appropriate. Values are presented as means ± SE unless otherwise stated.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
At a threshold volume, rapid-pulse as well as slow continuous pharyngeal water injection resulted in augmentation of UES pressure in all volunteers (Fig. 1). The threshold volume for inducing UES pressure increase averaged 0.1 ± 0.01 ml. The threshold volume for 2 of 10 volunteers was 0.05 ml, in 7 volunteers it was 0.1 ml, and in 1 volunteer it was 0.2 ml. Further increase in the volume of injected water above the threshold volume did not result in any significant additional increase in the UES pressure (Fig. 2). Similarly, slow continuous injection of water into the pharynx resulted in augmentation of UES resting pressure. The threshold volume for slow continuous injection (1.0 ± 0.2 ml) was significantly larger than that of rapid-pulse injection (P < 0.05). The magnitude of this augmentation was comparable to that induced by rapid-pulse injection (Fig. 2). The magnitude of UES pressure following rapid-pulse injection of threshold volumes of water into the pharynx averaged 76 ± 5 mmHg compared with the baseline preinjection value of 45 ± 2 mmHg (61 ± 13% increase). For slow continuous injection, it was 81 ± 6 mmHg compared with the baseline of 46 ± 2 mmHg (63 ± 9.0%).
|
|
In all, 120 rapid water injections for 0.05-, 0.1-, 0.2-, 0.3-, and 0.4-ml volumes were performed. In 17 instances, and in 7 volunteers, the UES pressure increase induced by water injection returned to baseline preinjection value before a swallow occurred. The duration of UES augmentation in these instances averaged 9.0 ± 3.0 s (range 4-45 s). In the remaining 103 instances, the UES pressure increase persisted until a swallow occurred. In these instances, the duration for UES pressure increase averaged 16 ± 4 s (range 2-40 s). For slow continuous injection, there was no return of the pressure to baseline before the occurrence of a swallow.
The effect of temperature of injected volumes on the UES pressure is shown in Fig. 3. Augmentation of UES resting tone by injection of water with three different temperatures was similar.
|
An example of the effect of topical pharyngeal anesthesia on the UES pressure response to pharyngeal water injection is shown in Fig. 4. After pharyngeal anesthesia, injection of various volumes of water into the pharynx did not result in any change in the UES pressure. The time interval between the injection of threshold volume and the onset of UES pressure increase averaged 1.1 ± 0.3 s (range 0-7 s). This duration was similar for all volumes and temperatures.
|
In all subjects, rapid-pulse injection of 0.5 ± 0.1 ml of water into the pharynx resulted in an irrepressible swallow. This threshold volume was significantly larger than the threshold volume that induced UES pressure augmentation (P < 0.01).
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In this study we determined the effect of pharyngeal stimulation by water injection on the resting tone of the UES. The study findings confirm the presence of a pharyngo-UES contractile reflex in humans. The afferent arm of this reflex most probably includes the pharyngeal mechanoreceptors and the glossopharyngeal nerve, although the contribution of the superior laryngeal nerve cannot be excluded. The efferent arm is undoubtedly the vagus nerve. The central pathway for this reflex is not currently known, but is probably different from those of deglutition because the contractile response to the stimulation of this reflex is the opposite of the relaxation response of the UES to a volitional, subconscious, or reflexive/pharyngeal swallow.
Except for the UES, pharyngeal water stimulation induces an inhibitory effect on the deglutitive apparatus; on the lower esophageal sphincter, its effect is complete or partial inhibition of the basal tone (9), and these inhibitions may be associated with gastroesophageal reflux (4, 10). Pharyngeal water stimulation is also capable of inhibiting the crura of the diaphragm (4). On the esophageal body, pharyngeal water stimulation inhibits the progression of the primary peristalsis (8), resulting in a halt in bolus transport (1). On the contrary, we found in this study that the effect of pharyngeal water stimulation on the UES is stimulatory, resulting in a significant increase in the resting UES pressure. It is conceivable that this contractile response of the UES may counteract the inhibitory effect of pharyngeal water stimulation on the rest of the deglutitive apparatus, thus preventing pharyngeal reflux of gastric and/or esophageal content. In addition, it may be postulated that this reflex may be activated during gastroesophagopharyngeal and/or esophagopharyngeal reflux events by contact of regurgitated material with pharyngeal mucosa, thus inducing an augmentation of UES resting pressure and possibly preventing further entry of refluxate into the pharynx. In this regard, the pharyngo-UES contractile reflex may be considered one of the airway-protective mechanisms against aspiration of gastric content.
It is known that stimulation of the pharynx by various stimuli results in contraction of the diaphragm as well as of the intercostal muscles, resulting in inhalation: the aspiration reflex (5, 7). Increase or decease in ambient pressure of the pharynx results in stimulation of rapidly adapting receptors of pharyngeal mucosa. These discharges have been recorded by single-fiber recording from the glossopharyngeal as well as the superior laryngeal nerves (2). Although in this study the effect of pharyngeal stimulation on respiration was not determined, during previous studies on its effect on esophageal peristalsis (7, 8), which were done with similar methodology, respiration was monitored and showed only a reduction of respiratory rate without evidence for induction of apnea or inhalation reflex. The pharyngo-UES contractile reflex is an example of digestive tract reflexes originating from the pharynx in humans. This same reflex has been documented in felines (3).
In the feline model, the afferent arc of this reflex was found to be the glossopharyngeus nerve because severance of this nerve abolished the reflex (3). The efferent arc was the cricopharyngeal branch to the pharyngoesophageal nerve. Contraction of the cricopharyngeal muscle induced by pharyngeal mechanical stimulation was short lived, indicating that the reflex was being mediated through rapidly adjusting mechanoreceptors.
The duration of reflex contraction of UES after pharyngeal water injection in humans determined in this study is significantly longer than that found in the feline model. Commonly, it was long enough until a spontaneous swallow occurred. However, it needs to be considered that in feline studies we used pressure application and a light touch that had a distinct beginning and end. In the present study, although the onset and completion of water injection were distinct, the injected volume stayed in the pharynx until it was cleared by a swallow. This dwelling of the injected water and its continuous stimulation of the pharynx may account for the longer duration of UES contraction and indicate that responsible receptors in the pharynx stimulated by this technique are slowly adjusting. These slowly adapting receptors recruited for stimulation of the pharyngo-UES contractile reflex in humans seem to be different from those reported in the literature as responsible for the aspiration reflex (2, 5), which consists of rapidly adapting receptors.
In summary, stimulation of the pharynx in humans by injection of minute amounts of water results in a significant increase in resting UES pressure: the pharyngo-UES contractile reflex. Threshold volume for stimulation of the pharyngo-UES contractile reflex is significantly lower than that for a pharyngeal swallow. The degree of pressure increase due to activation of this reflex in normal young humans is not volume or temperature dependent. Loss of pharyngeal sensation abolishes this reflex.
![]() |
ACKNOWLEDGEMENTS |
---|
This work was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK-25731 and a Merit Review Grant from the Department of Veterans Affairs.
![]() |
FOOTNOTES |
---|
Address for reprint requests: R. Shaker, Div. of Gastroenterology and Hepatology, Froedtert Memorial Lutheran Hospital, 9200 W. Wisconsin Ave., Milwaukee, WI 53226.
Received 24 January 1997; accepted in final form 24 June 1997.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Bardan, E.,
P. Xie,
J. Ren,
K. Dua,
and
R. Shaker.
Effect of pharyngeal water stimulation on esophageal peristalsis and bolus transport.
Am. J. Physiol.
272 (Gastrointest. Liver Physiol. 35):
G265-G271,
1997
2.
Hwang, J. C.,
W. M. St. John,
and
D. Bartlett, Jr.
Receptors responding to changes in upper airway pressure.
Respir. Physiol.
55:
355-366,
1984[Medline].
3.
Medda, B. K.,
I. M. Lang,
R. Layman,
W. J. Hogan,
W. J. Dodds,
and
R. Shaker.
Characterization and quantification of a pharyngo-UES contractile reflex in cats.
Am. J. Physiol.
267 (Gastrointest. Liver Physiol. 30):
G972-G983,
1994
4.
Mittal, R. K.,
C. Chiareli,
J. Liu,
and
R. Shaker.
Characteristics of lower esophageal sphincter relaxation induced by pharyngeal stimulation with minute amounts of water.
Gastroenterology
111:
378-384,
1996[Medline].
5.
Nail, B. S.,
G. M. Sterling,
and
J. G. Widdicombe.
Epipharyngeal receptors responding to mechanical stimulation.
J. Physiol.
204:
91-98,
1967.
6.
Shaker, R.,
J. Ren,
Z. Zamir,
A. Sarna,
J. Liu,
and
Z. Sui.
Effect of aging, position, and temperature on the threshold volume triggering pharyngeal swallows.
Gastroenterology
107:
396-402,
1994[Medline].
7.
Tomori, Z.
Pleural, tracheal and abdominal pressure variations in defensive and pathologic reflexes of the respiratory tract.
Physiologia Bohemoslov
14:
84-94,
1965.
8.
Trifan, A.,
J. Ren,
R. Arndorfer,
C. Hofmann,
E. Bardan,
and
R. Shaker.
Inhibition of progressing primary esophageal peristalsis by pharyngeal water stimulation in humans.
Gastroenterology
110:
419-423,
1996[Medline].
9.
Trifan, A.,
R. Shaker,
J. Ren,
R. K. Mittal,
K. Saeian,
K. Dua,
and
M. Kusano.
Inhibition of resting lower esophageal sphincter pressure by pharyngeal water stimulation in humans.
Gastroenterology
108:
441-446,
1995[Medline].
10.
Xie, P.,
J. Ren,
E. Bardan,
R. K. Mittal,
Z. Sui,
and
R. Shaker.
Frequency of gastroesophageal reflux events induced by pharyngeal water stimulation in young and elderly subjects.
Am. J. Physiol.
272 (Gastrointest. Liver Physiol. 35):
G233-237,
1997