Characterization and mechanisms of the pharyngoesophageal
inhibitory reflex
Ivan M.
Lang,
Bidyut K.
Medda,
Junlong
Ren, and
Reza
Shaker
Dysphagia Institute and Department of Medicine, Medical College of
Wisconsin, Milwaukee, Wisconsin 53226
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ABSTRACT |
The objectives
of this study were to identify and to characterize the
pharyngoesophageal inhibitory reflex (PEIR) in an animal model.
Thirty-one cats (2.4-5.0 kg) were anesthetized using
-chloralose (45 mg/kg ip), and esophageal peristalsis was recorded
manometrically. Secondary peristalsis was activated by rapid air
injection (8-20 ml) at midesophagus or slow infusion of water
through the manometric catheters. Neither stimulus activated primary
peristalsis. The PEIR was activated by rapid water injection or focal
mechanical stimulation of the pharynx. Rapid air injection activated
secondary peristalsis in 92% of the trials, and slow water infusion
activated 1 secondary peristalsis every 3.2 min. Pharyngeal stimulation by 0.3, 0.5, 0.8, or 1.0 ml of water inhibited or blocked ongoing secondary peristalsis in 67, 82, 97, or 93% of trials, respectively. Mechanical stimulation of the posterior wall of the pharynx with 11-20 g pressure attenuated secondary peristalsis in 96% of the trials or blocked secondary peristalsis in 41% of the trials. Centripetal electrical stimulation at 30 Hz, 0.2 ms, 2 V for 4 s of the
superior laryngeal (SLN) or glossopharyngeal (GPN) nerves blocked or
inhibited secondary peristalsis in 100% of the trials. Bilateral
transection of the GPN (n = 8), but
not the SLN (n = 6), blocked the PEIR.
Anesthetization of the pharyngeal mucosa using lidocaine (2%) blocked
the PEIR (n = 3). We
concluded that 1) the PEIR exists in
the cat, 2) mechanical stimulation
of the pharynx more strongly activates the PEIR than water,
3) activation of either SLN or GPN
afferents attenuates ongoing secondary peristalsis, 4) the receptors mediating the PEIR
are located in the pharyngeal mucosa, and
5) both SLN and GPN contribute to
the PEIR, but the GPN is the major afferent limb of this reflex.
pharynx; esophagus; glossopharyngeal nerve; superior laryngeal
nerve; esophageal peristalsis; secondary peristalsis
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INTRODUCTION |
IN PRIOR STUDIES WE FOUND that the injection of small
volumes (0.16 ± 0.01 ml threshold) of water into the pharynx
inhibited resting lower esophageal sphincter (LES) pressure (25),
increased the frequency of gastroesophageal reflux events (29),
inhibited the progressing primary esophageal peristalsis of dry (24)
and bolus (3) swallows, halted progression of barium boluses through the esophagus (3), and inhibited secondary peristalsis activated by
esophageal balloon inflation or air injection (2). Topical anesthesia
of the pharynx using 4% lidocaine blocked these effects (24),
indicating that the receptors for these responses were probably located
in the pharyngeal mucosa.
The effects of pharyngeal stimulation on the function of the esophagus
and LES have been studied in human subjects, and the limitations
imposed by these experiments have precluded investigation of the
mechanisms of these effects. Therefore, in these studies we have
developed an animal model of the pharyngeal inhibition of esophageal
function and have conducted experiments to
1) determine whether a reflex
mediates the inhibition of esophageal function by pharyngeal
stimulation, 2) characterize and
quantify the effects of this reflex on esophageal function,
3) identify and locate the receptors
mediating this reflex, and 4)
identify the afferent neural pathways mediating this reflex.
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METHODS |
Animal preparation.
We studied 31 cats weighing from 2.4 to 5.0 kg that were anesthetized
with
-chloralose (45 mg/kg ip). The cats were placed supine, and the
abdominal cavity was opened. A fistula of the gastric corpus was made
to allow evacuation of gastric contents during the experimental session
and introduction of a manometric catheter assembly for recording
esophageal peristalsis. The catheter was fixed in place by suturing the
catheter assembly to the abdominal skin. A second catheter was placed
in the oral cavity so that the tip of the catheter lay at the level of
the hypopharynx. This catheter was used to inject small amounts of
water into the pharynx. A ventral midline incision was made in the
cervical region and further surgical preparation varied with the
protocol. For those studies of neural control, the superior laryngeal
(SLN) and glossopharyngeal (GPN) nerves were isolated, and ligatures
were placed loosely around them for later section or stimulation. For
studies in which pressure was applied to the pharynx, the pharynx was
exposed by opening spaces between the thyroid and cricoid cartilages
through the cricothyroid ligament and between the hyoid bone and
thyroid cartilage through the thyrohyoid muscle. In some experiments
electromyography (EMG) electrodes were placed on the geniohyoideus,
mylohyoideus, or cricopharyngeus muscle to monitor EMG activity as an
index of swallowing. In all animals a cannula was placed in the femoral artery to monitor arterial pressure and one was placed in the femoral
vein for the infusion of lactated Ringer solution to maintain arterial
pressure above 75 mmHg.
Manometric recording of esophageal peristalsis.
The intraluminal pressures of the esophagus were recorded with use of
catheter assemblies with either five or eight sideholes. The middle
port of each catheter assembly was used for injection of air into the
esophagus for initiation of secondary peristalsis. The diameter of each
assembly was 3 and 5 mm, respectively. The most distal port was placed
2 cm above the LES. Each catheter of the assembly was perfused with
distilled water at 0.2 ml/min using an Arndorfer hydraulic pump. Side
pressures were recorded using Statham pressure transducers connected to
a Grass model 7 polygraph and recorded on Hewlett-Packard
Instrumentation tape recorder (no. 3968A).
EMG of pharyngeal muscles.
In 11 cats EMG activity was recorded from the geniohyoideus
(n = 4), mylohyoideus
(n = 4), or cricopharyngeus
(n = 3) to help distinguish between
primary (i.e., swallowing) and secondary peristalsis. Bipolar
Teflon-coated stainless steel wires (AS 632; Cooner Wire, Chatsworth,
CA) bared for 2-3 mm were placed in each muscle, and the wires
were attached to Grass P15 preamplifiers. The electrical activity was
filtered (0.1-3.0 kHz, 0.5 amplitude) and amplified (10 times)
before feeding into a Grass 7P3 preamplifier. The EMG activities of the
geniohyoideus and mylohyoideus are activated during primary peristalsis
and pharyngeal swallows but not secondary peristalsis, and therefore
were used as an index of the presence of primary peristalsis or
pharyngeal swallows. The EMG activity of the cricopharyngeus increases
during primary and secondary peristalsis but not pharyngeal swallows,
and the response during secondary peristalsis is delayed. Also, during
primary peristalsis the cricopharyngeus EMG is inhibited for a short
period of time corresponding to upper esophageal sphincter (UES)
relaxation, whereas no cricopharyngeus EMG inhibition occurs during
secondary peristalsis.
Initiation of secondary peristalsis.
In all cats we stimulated secondary peristalsis by two methods:
1) slow esophageal fluid infusion
from the recording catheters or 2)
rapid air injection (8 to 20 ml) into the mid [port 3 of the
5-lumen catheter or port 5 (from the LES) of the 8-lumen
catheter] esophagus. Both stimuli activated secondary peristalsis
in all cats, but rapid air injection was more reliable and predictable and did not fatigue as readily. At no time did these stimuli activate primary peristalsis as determined by EMG recordings of the pharyngeal musculature.
Stimulation of pharynx (activation of PEIR).
In all cats the pharynx was stimulated by rapid injection of water at
0.1-1.0 ml into the pharynx through a prepositioned and fixed
small bore catheter (0.02 × 0.06 in. S-54 HL, biocompatible Tygon
tubing). In six cats the pharynx was stimulated by direct pressure by
wooden probe of 3-mm diameter. In eight cats a stainless steel probe of
3-mm diameter connected to a pressure transducer was used to focally
activate the pharyngeal receptors at known pressures. This pressure
probe was constructed from a 250-µl Hamilton glass syringe, which was
connected to a Statham pressure transducer. The pressure probe was
calibrated by pressing on a digital scale (Sartorius Universal U4800P).
Different areas of the pharynx, i.e., soft palate, nasopharynx, and
hypopharynx, were probed at different pressures. In one cat the
pharyngeal mucosa was gently stroked using a wooden cotton-tipped
applicator of about 5-mm diameter.
Anesthesia of pharyngeal mucosa.
In three cats 1 ml of lidocaine (2%) was placed directly on the
hypopharynx through a syringe. The trachea of the cats was cannulated
before this procedure to prevent aspiration of lidocaine. Care was
taken to prevent activation of pharyngeal swallows, which would have
removed lidocaine from the region. Ten minutes after application of the
lidocaine, the pharynx and esophagus were suctioned and the effects of
pharyngeal stimulation by water or pressure on secondary peristalsis
were determined. The pharynx was then flushed and suctioned with
100-200 ml of 0.9% NaCl for 15 min, and the pharyngoesophageal
inhibitory reflex (PEIR) was tested again 30 min after washing
lidocaine from the pharynx.
Transection of GPN and SLN.
In 12 animals we investigated the role of the GPN
(n = 8) or SLN
(n = 6) in the mediation of the PEIRs.
In two animals both nerves were transected with the SLN transected
first. The SLN was identified by its branching from the caudal pole of
the nodose ganglion and its innervation of the junction of the
cricopharyngeus and thyropharyngeus muscles. The SLNs were severed
bilaterally at the level of their innervation of the pharyngeal muscles
about 2 cm cranial to the pharynx (Fig. 1).
The GPN was identified just medial to the tympanic bulla and identified
as the small nerve rostral to the internal jugular vein and converging
with the vagus, accessory, and the hypoglossal nerves toward the
jugular foramen, and which branched in the form of a "T" about 1 cm from the tympanic bulla. The GPNs were severed bilaterally just
cranial to their branching point (Fig. 1).

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Fig. 1.
Diagram of innervation of pharynx in cat. A, artery; M, muscle; N,
nerve. Jagged lines on cranial (superior) laryngeal (SLN) and
glossopharyngeal (GPN) nerves indicate where these nerves were
sectioned. SLN of humans is referred to as cranial laryngeal nerve in
animals.
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Electrical stimulation of nerves.
In seven animals we investigated the effects of unilateral centripetal
electrical stimulation of the SLN (n = 7) or GPN (n = 2) on esophageal
peristalsis. The central ends of the nerves were stimulated after
cutting at the same point they were severed in the experiments
previously described. The nerves were stimulated using square-wave
pulses (Grass S88 stimulator) at 2 V, 0.2 ms, and 30 Hz for 1-9 s.
Statistical methods.
Differences in mean values were tested using Student's
t-test, and differences in attribute
data were tested using
2.
P
0.05 or less was considered
statistically significant.
Identification and quantification of PEIR.
Three or four secondary peristalses were induced by slow fluid infusion
or by rapid injection of air (8-20 ml) into the esophagus. After
control responses of secondary peristalsis were obtained, the effects
of rapid injection of small volumes of water (0.1, 0.3, 0.5, 0.8, and
1.0 ml) on secondary peristalsis were determined. The incidence of PEIR
at each volume was determined. A positive response was defined as
1) blockade of the progressing
peristaltic wave or 2) inhibition of
the magnitude of the peristaltic pressure at one port or more by at
least 50% without blockade of the progressing peristaltic wave. The
secondary peristalsis activated by either method tended to fatigue
after a few hours of testing, and therefore it was not possible to
conduct all protocols in all animals.
The effect of activation of the PEIR by pharyngeal water injection was
tested at different times during the progression of the peristalsis to
determine the effect of PEIR at different levels of the esophagus. In
particular, we were interested in comparing the effects on the proximal
striated muscle portion to the distal smooth muscle portion of the
esophagus.
After characterizing the effects of pharyngeal injection of water, we
determined the location of the receptors for activating the PEIR by
directly applying pressure over small areas (3-mm diam circular area)
of the mucosa. We compared the effects of pressure on the dorsal wall
of the hypopharynx with the soft palate and the nasopharynx.
Role of various afferent nerves in initiation of PEIR.
After activating the PEIR two to four times by water injection or
direct pressure, we determined the effect of transecting the GPN or SLN
on initiation of the PEIR.
Role of pharyngeal mucosa in initiation of PEIR.
After activating the PEIR two to four times by water injection or
direct pressure, we determined the effect of applying 2% lidocaine on
the pharyngeal mucosa on initiation of the PEIR. The PEIR was tested 15 min after application of the lidocaine and 30 min after washing the
lidocaine from the mucosa using 0.9% NaCl.
Effect of centripetal electrical stimulation of GPN or SLN on
secondary peristalsis.
We activated the secondary peristalsis by slow fluid infusion of water
or the rapid injection of air into the esophagus three or four times.
After isolation of either the GPN (n = 2) or the SLN (n = 7) on one side, the
nerve was stimulated electrically, just after activation of secondary
peristalsis by either method to determine its effect on the PEIR.
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RESULTS |
Initiation of esophageal peristalsis.
Slow infusion of water into the esophagus activated secondary
peristalsis once every 3.2 ± 0.5 (n = 27) min for the first three or
four occurrences. Rapid injection of air (8-20 ml) into the
midesophagus activated secondary peristalsis in 92% of the trials
(Fig. 2). The incidences of peristalsis
induced by either method decreased over the duration of the experiment.
Neither stimulus activated primary peristalsis, but pharyngeal swallows were observed frequently. The amplitudes of secondary peristalsis of
the striated or smooth muscle portions of the esophagus activated by
slow infusion of water or rapid injection of air were not significantly (t
0.97, P > 0.05) different (Table
1). The velocity of these peristaltic
events was also not significantly different: 2.0 ± 0.1 cm/s for
rapid air-induced and 2.1 ± 0.1 cm/s for slow water-induced secondary peristalsis (t = 0.71, P > 0.05).

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Fig. 2.
Effect of pharyngeal stimulation by water on secondary peristalsis
activated by rapid air injection. Secondary peristalses were activated
by injection of 10 ml of air into midesophagus. LES, lower esophageal
sphincter; ESO, esophagus. Black boxes at bottom of figure indicate
time of administration of appropriate stimulus. Note blockade of
ongoing peristalsis by pharyngeal injection of 0.3 ml or more water and
postinhibitory peristalsis after pharyngeal injection of 0.8 ml of
water.
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Identification and quantification of PEIR.
Pharyngeal stimulation by injection of 0.3, 0.5, 0.8, or 1.0 ml of
water inhibited or blocked ongoing secondary peristalsis in 67, 82, 97, or 93% of trials, respectively. Focal pressure on dorsal wall of the
pharynx using a wooden probe or applying >20 g pressure using a
stainless steel probe blocked or inhibited esophageal peristalsis in
100% of the trials (Table 2). In some cases (41 of 182 attempts in 23 animals) shortly (<20 s) after the
ongoing peristalsis is blocked a second separate peristaltic wave,
i.e., postinhibitory peristalsis, was initiated (Fig. 2, last panel).
Pharyngeal stimulation blocked or attenuated secondary peristalsis
whether the secondary peristalsis was in the striated muscle or smooth
muscle portion of the esophagus (Fig. 3).
However, the incidence of blockade of secondary peristalsis by this
PEIR (at or above the threshold stimulus) was greater
(
2 = 83.2, P < 0.05) in the striated (91%)
muscle portion of the esophagus, and the incidence of peristaltic
attenuation was greater in the smooth (90.5%) muscle portion of the
esophagus (P < 0.05). Of
the blocked occurrences of peristalsis, a postinhibitory peristaltic wave occurred in 50% (40 of 81) of the trials after blockade of the
striated muscle peristalsis and in 25% (1 of 4) of the trials after
blockade of smooth muscle peristalsis, but this difference was not
significant (
2 = 0.373, P > 0.05).

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Fig. 3.
Effect of pharyngeal stimulation on secondary peristalsis: striated vs.
smooth muscle. Control secondary peristalsis was activated by slow
fluid injection into esophagus, whereas the other secondary peristalses
were activated by injection of 20 ml of air into midesophagus. Note
that ongoing peristalsis was blocked by pharyngeal stimulation whether
it was in smooth or striated muscle portions of esophagus. Smooth
muscle esophagus of cat extends to 6-8 cm above LES.
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Focal pressure of 3-mm diameter areas of the pharynx attenuated or
blocked the ongoing secondary peristalsis when applied to the
hypopharynx but not the soft palate or nasopharynx (Fig. 4). Esophageal peristalsis was inhibited in
80% (8 of 10 attempts, 3 of 3 animals) of trials by a force of
1-10 g and in 96% of trials (26 of 27 attempts, 8 of 8 animals)
by a force from 11 to 20 g. Esophageal peristalsis was blocked in 0%
of trials (0 of 10 attempts, 0 of 3 animals) by a force from 1 to 10 g,
in 41% of trials (11 of 27 atempts, 3 of 8 animals) by a force from 11 to 20 g, and in 80% of trials (16 of 20 attempts, 5 of 6 animals) by a
force from 21 to 40 g. The magnitude of applied pressure was related to
the magnitude of the esophageal inhibition (Fig.
5). In addition stroking the mucosa using a
cotton-tipped applicator with little pressure also activated the PEIR
(Fig. 6).

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Fig. 4.
Comparison of effects of focal pressure on pharynx, nasopharynx, or
soft palate on secondary peristalsis. PEIR, pharyngoesophageal
inhibitory reflex. Note that similar force applied to different areas
of oropharynx had different effects on ongoing secondary peristalsis.
No PEIR was activated by stimulation of nasopharynx or soft
palate.
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Fig. 5.
Stimulus-response relationship of PEIR activated by focal pressure. F,
dorsal wall of pharynx between vocal cords and soft palate (13). Note
that higher force on pharynx caused greater inhibition of ongoing
esophageal peristalsis.
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Fig. 6.
Activation of PEIR by pharyngeal mucosal stimulation without pressure.
Secondary peristalses were activated by injection of 12 ml air into
esophagus. Note that stroking mucosa with little pressure had similar
effect to focal pressure on inhibiting ongoing secondary peristalsis.
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Effects of transection of GPN or SLN on PEIR.
We found that bilateral transection of the SLN did not block the PEIR
activated by water injection (
2 = 0.403, P > 0.05) or focal pressure
(
2 = 1.783, P > 0.05) in any of the cats
(n = 6) examined (Fig. 7 and Table 3),
but did reduce (58 vs. 11%,
2 = 16.2, P < 0.05) the effectiveness
of water injection to block esophageal peristalsis (Table 3). Bilateral
transection of the GPN blocked or reduced the PEIR activated by water
injection (
2 = 114.9, P < 0.05) or focal pressure
(
2 = 34.1, P < 0.05) in all cats
(n = 8) examined (Fig.
8 and Table 3). In two of these cats the
SLNs had been transected previously. Although the effect of GPN
transection on focal pressure-induced PEIR (45%) was greater than on
water injection-induced PEIR (17%), this difference was not
statistically significant (
2 = 3.27, P = 0.07; Table 3).

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Fig. 7.
Effect of transection of SLNs on PEIR. Note that transection of SLN
bilaterally did not affect PEIR.
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Role of pharyngeal mucosa in initiation of PEIR.
Anesthesia of the pharyngeal mucosa with lidocaine blocked the
initiation of the PEIR by water injection in all animals
(n = 3) tested (Fig.
9 and Table 3) and greatly reduced (100 vs. 33%) the effectiveness of focal pressure
(
2 = 41.8, P < 0.05).

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Fig. 9.
Effect of mucosal anesthesia using lidocaine on PEIR. Note that mucosal
anesthesia blocked PEIR due to pharyngeal water injection or focal
pressure.
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Effect of centripetal electrical stimulation of SLN or GPN on
secondary peristalsis.
Centripetal electrical stimulation at 30 Hz, 0.2 ms, 2 V for 4.0 ± 0.2 s of the SLN or GPN inhibited or blocked secondary peristalsis in
100% of the trials (Fig. 10 and Table
4). The effects of electrical stimulation
of the SLN and GPN on secondary peristalsis were not significantly
different (
2 = 2.124, P = 0.145), but only SLN stimulation
resulted in postinhibitory secondary peristalsis (Table 4). We also
found that centripetal electrical stimulation of the SLN facilitated
the activation of secondary peristalsis by rapid air injection (Fig.
11); this effect was not tested with GPN
stimulation.

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Fig. 10.
Effects of centripetal electrical stimulation of right SLN or GPN (RSLN
or RGPN) on PEIR. Note that centripetal electrical stimulation of SLN
or GPN inhibited ongoing peristalsis.
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Fig. 11.
Facilitation of initiation of secondary peristalsis by centripetal
electrical stimulation of SLN. Note that 30 s after centripetal
electrical stimulation of SLN subthreshold esophageal stimulus (rapid
injection of 10 ml of air) initiated secondary peristalsis.
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DISCUSSION |
We found that stimulation of the pharynx blocked or attenuated the
progression of secondary esophageal peristalsis in cats as it does in
humans (2). This inhibition occurred whether the peristalsis was
initiated by slow water infusion into the esophagus or rapid air
injection. Experimental limitations prevented us from examining the
effects of pharyngeal stimulation on primary peristalsis, because these
chloralose-anesthetized cats did not exhibit primary peristalsis.
However, because pharyngeal stimulation in humans inhibits esophageal
peristalsis of primary (24) as well as secondary peristalsis (2) it is
probable that the same occurs in animals. The threshold volume (0.75 ml) for activation of the PEIR by pharyngeal water injection in humans
(3) was very similar to the volume (0.8 ml) of water needed to block
the PEIR in cats in 90% of the trials. Although the absolute volumes were similar the volume per surface area of pharynx is larger in the
cats. This difference may have been due to
1) a different position of the
stimulating catheter, 2) chloralose
anesthesia, or 3) a difference in
the sensitivity of these two species to this stimulus. We think the
major differences are the effects of anesthesia and location of the
catheter, because no sedation or anesthesia was used in the human
experiments and the amount of direct force (>10 g) and area (3-mm
diam) of mucosa needed to activate this reflex in cats was small.
The PEIR in cats, as in humans (3), occurred in both the striated and
smooth muscle portion of the esophagus, although the effect was
stronger in the striated than the smooth muscle portion. That is,
whereas 91% of stimuli applied when peristalsis was in the striated
muscle portion of the esophagus resulted in blockade, only 10% of
stimuli applied when peristalsis was in the smooth muscle portion
resulted in blockade. Similarly, in humans (3) the threshold for
activation of the PEIR was higher for blocking peristalsis in the
smooth muscle than the striated muscle portion of the esophagus. The
lesser effectiveness of pharyngeal stimulation on the smooth muscle
portion of the esophagus may be due to the more autonomous nature of
the smooth muscle esophagus. Peristalsis of the smooth muscle unlike
the striated muscle esophagus is controlled not only by the central
nervous system but also by myogenic and enteric neural mechanisms (6,
9, 17) and is capable of propagating peristalsis after extrinsic
denervation (4, 10, 18, 23). Our findings suggest that either
1) the PEIR is less effective in
inhibiting smooth muscle peristalsis at a central or peripheral site or
2) the PEIR acts at a central rather
than peripheral level to inhibit vagal control of peristalsis. We
concluded that the second possibility is more likely, and this issue is
discussed in greater detail below.
The effects of pharyngeal stimulation on ongoing esophageal peristalsis
are related not only to the location of the stimulus in the pharynx but
also to the strength of the stimulus. Larger injection volumes or
stronger focal pressures on the pharynx caused greater inhibition of
secondary peristalsis. However, whereas direct focal stimulation of the
hypopharynx inhibits esophageal peristalsis similar stimulation of the
nasopharynx or soft palate had no effect on secondary peristalsis. This
contrasts sharply with the pharyngo-UES contractile reflex which has
receptors in hypopharynx as well as the soft palate and nasopharynx
(13). Comparison of the distribution receptors of these two reflexes suggests that the PEIR probably has a role in digestive tract functions
only, whereas the pharyngo-UES contractile reflex may have both
respiratory and digestive tract functions.
Transection of the GPN greatly attenuated the effectiveness of the
PEIR. After GPN transection pharyngeal stimulation failed to block
esophageal peristalsis but was capable in some instances (<50% of
attempts) of reducing the magnitude of the peristaltic contractions. On
the other hand transection of the SLN only partially attenuated the
PEIR. After SLN transection the only change observed was a reduction in
the incidence of blocked peristalsis due to pharyngeal water injection.
We conclude that the PEIR is mediated through afferent fibers in both
the SLN and GPN but primarily in the GPN. This is in contrast to the
pharyngo-UES contractile reflex which is mediated by the GPN only (13).
Centripetal electrical stimulation of the GPN or SLN blocked or
inhibited secondary peristalsis. This finding corroborates prior
studies (5, 7, 11). Insufficient numbers of animals in which the GPNs
were stimulated were obtained to statistically determine differences
between GPN and SLN stimulation. It is striking, however, that although
SLN transection had minor effects on blocking the PEIR, centripetal
electrical stimulation of the SLN had profound inhibitory effects on
secondary peristalsis. These findings suggest that
1) the SLN may mediate esophageal
inhibition due to activation of an additional reflex or
2) the swallow pathways activated by SLN stimulation may also activate peristaltic inhibition (i.e., SLN
stimulation may cause peristaltic inhibition through deglutitive inhibition). We prefer the second suggestion because there is no known
additional esophageal inhibitory reflex mediated by the SLN, but
deglutitive inhibition is a well-known phenomenon.
Centripetal electrical stimulation of the SLN lowered the threshold for
subsequent activation of secondary peristalsis. A similar facilitative
effect on primary peristalsis activated by afferent nerve stimulation
was observed previously (5, 27). Prior studies indicate that SLN and
GPN afferents converge on medullary swallowing neurons of the nucleus
tractus solitarius (5, 16), which may explain facilitation of the
effects of centripetal electrical stimulation of the SLN and GPN on
primary peristalsis. Secondary peristalsis, however, is mediated by
vagal afferents, which may suggest additional convergence and
facilitation of vagal sensory nuclei by SLN afferents or convergence
and facilitation at a pattern generator for esophageal peristalsis.
Convergence of SLN and GPN afferents on NTS neurons (possibly vagal
sensory nuclei) have been identified (21), but the central control of secondary peristalsis has received little attention in the literature.
Local anesthesia of the pharyngeal mucosa using lidocaine blocked the
PEIR. These results confirm prior studies in humans (24). In addition,
we found that stroking the pharyngeal mucosa with little pressure
strongly activated the PEIR. These findings indicate that the receptors
mediating this reflex are probably located in the pharyngeal mucosa.
We have located the receptors and afferent pathways mediating the PEIR,
but the nature of the inhibition or identification of the efferent
pathway is unknown. The observed inhibition of the secondary
peristalsis may occur at the level of the central nervous system or at
the periphery. Considering that peristalsis of the striated portion of
the esophagus is controlled by the central nervous system and not the
enteric nervous system (4, 9, 10, 17, 23) and inhibitory nerves to
striated muscles have not been demonstrated
[NADPH-diaphorase-positive nerve fibers eminating from enteric
neurons (15) have been associated with endplates of rat esophagus
(which is striated muscle), but the function of these fibers is
unknown], it is likely that the inhibition observed in the
striated muscle portion of the esophagus occurred at the level of the
central nervous systen. Direct evidence for a central effect of
GPN-activated inhibition of esophageal peristalsis was demonstrated by
the finding that centripetal electrical stimulation of the GPN
inhibited or prevented initiation of swallow-related medullary
esophageal interneuron activity (5). Therefore, we conclude that the
inhibition of peristalsis of the striated muscle portion of the
esophagus during the PEIR is probably manifested in the central nervous
system rather than the periphery.
The mechanism of inhibition of the smooth muscle esophagus is more
complicated than the striated muscle esophagus, because evidence
suggests that smooth muscle esophageal peristalsis may also be
controlled by myogenic (28) and enteric neural mechanisms (6). We found
that the PEIR also blocked secondary peristalsis in the smooth muscle
portion of the esophagus, although the effect was more pronounced in
the striated muscle portion. Assuming that esophageal inhibition during
the PEIR does not differ for different parts of the esophagus, our
findings suggest that the effect of the PEIR on the smooth muscle
esophagus is also probably mediated at a central site. Although the
smooth muscle esophagus is capable of propagating a peristaltic
contraction after extrinsic denervation (4, 10, 18, 23), under
physiological conditions the smooth muscle esophagus receives central
vagal input in a sequential pattern corresponding to the propagating
esophageal peristaltic wave of contraction similar to (but weaker than)
that of the striated muscle portion during esophageal peristalsis (8,
19). Our findings and the literature are most consistent with the
concept that esophageal peristalsis of the smooth muscle portion of the esophagus is controlled at three levels:
1) muscle,
2) enteric nervous system, and
3) central nervous system but that
the central control is more significant under physiological conditions.
Therefore, we suggest that the PEIR blocks the central input to the
esophagus resulting in blockade or inhibition of peristalsis in the
smooth muscle as well as striated muscle esophagus. The extent of
inhibition of the smooth muscle esophagus during the PEIR may depend on
the relative contribution of peripheral mechanisms to the propagation of the peristaltic wave. Definitive conclusions regarding the specific
roles of the central and peripheral mechanisms controlling smooth
muscle esophageal peristalsis awaits further investigation.
Esophageal peristalsis is inhibited during a series of repetitive
swallows until the last swallow (1, 11, 14, 26). This inhibitory
phenomenon, i.e., deglutitive inhibition, is important because without
this inhibition an ongoing peristaltic wave would be obstructive to the
subsequent swallowed bolus. A similar inhibitory phenomenon was
observed in these studies and in prior studies (5, 7) during
centripetal electrical stimulation of the GPN or SLN. A pertinent
consideration here is whether the PEIR we observed plays a role in or
perhaps is the mechanism by which repetitive swallowing inhibits the
esophageal peristalsis. Although our studies do not resolve this issue
there are many similarities between the PEIR and deglutitive
inhibition: 1) both inhibitions affect the striated muscle more than the smooth muscle esophagus (3, 9, 26 ), 2) swallowing and the PEIR are
mediated by the GPN and SLN (7, 22, 27), and
3) both effects can result in postinhibitory esophageal peristalsis (1, 9, 20). Two explanations seem
possible: 1) the PEIR and
deglutitive inhibition may have different afferent pathways but similar
physiological effects and functions or
2) the PEIR is part of and comprises the afferent limb of the reflex inhibition observed during deglutitive inhibition. Further studies are needed to resolve these issues.
In conclusion, the PEIR occurs in cats and the receptors for this
reflex are located in the mucosa of hypopharynx but not the soft palate
or nasopharynx. The afferent pathways for this reflex include the GPN
and SLN but primarily the GPN. The peristaltic inhibition by this
reflex is probably manifested at a central site, and the PEIR may be
related to deglutitive inhibition.
 |
ACKNOWLEDGEMENTS |
These studies were funded in part by the National Institutes of
Health Grants RO1-DC-00669 and RO1-DK-25731.
 |
FOOTNOTES |
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests: I. M. Lang, Dysphagia Research
Laboratory, Medical College of Wisconsin, 8701 Watertown Plank Rd.,
Milwaukee, WI 53226.
Received 4 May 1998; accepted in final form 2 July 1998.
 |
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