INTRODUCTION

Top Abstract Introduction Methods Results Discussion References

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.

	METHODS

Top Abstract Introduction Methods Results Discussion References

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).

View larger version (54K): [in this window] [in a new window]   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.

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.

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.

	RESULTS

Top Abstract Introduction Methods Results Discussion References

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).

View larger version (17K): [in this window] [in a new window]   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.

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).

View larger version (21K): [in this window] [in a new window]   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.

View larger version (18K): [in this window] [in a new window]   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.

View larger version (20K): [in this window] [in a new window]   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.

View larger version (19K): [in this window] [in a new window]   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.

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).

View larger version (23K): [in this window] [in a new window]   Fig. 7.   Effect of transection of SLNs on PEIR. Note that transection of SLN bilaterally did not affect PEIR.

View larger version (19K): [in this window] [in a new window]   Fig. 8.   Effect of transection of GPNs on PEIR. Note that transection of GPNs bilaterally blocked PEIR.

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).

View larger version (23K): [in this window] [in a new window]   Fig. 9.   Effect of mucosal anesthesia using lidocaine on PEIR. Note that mucosal anesthesia blocked PEIR due to pharyngeal water injection or focal pressure.

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.

View larger version (21K): [in this window] [in a new window]   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.

View larger version (23K): [in this window] [in a new window]   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.

	DISCUSSION

Top Abstract Introduction Methods Results Discussion References

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.