Facilitation of the swallowing reflex with bilateral afferent input from the superior laryngeal nerve.

To determine the cooperative effect of laryngeal afferent signals on the swallowing reflex, we examined whether afferent signals originating from the left and right superior laryngeal nerve (SLN) modulates elicitation of the swallowing reflex in urethane-anesthetized rats. Mylohyoid electromyographic activity was recorded to quantify the swallowing reflex. The onset latency of the swallowing reflex and the time intervals between successive swallows were used to quantify and compare the effects of unilateral and bilateral electrical stimulations of the SLN. The mean latency of the first swallow and the mean time interval between swallows evoked with low frequency stimulation were both significantly different between unilateral and bilateral stimulations of the SLN. These findings suggest that facilitatory effect of afferent signals originating from the SLN bilaterally increase the motoneuronal activity in the medullary swallowing center and enhance the swallowing reflex.

Facilitation of reflex swallowing from the pharynx and larynx.

To evaluate the cooperative effect of afferent signals from the pharynx and larynx on reflex swallowing, the interactive effect of afferent signals from the pharyngeal branch of the glossopharyngeal nerve (GPN-ph) and superior laryngeal nerve (SLN) was analyzed in detail in urethane-anesthetized rats. The electromyographic activity of the mylohyoid muscle was recorded as an indicator of swallowing activity. The onset latency of reflex swallowing was measured to evaluate the effects of electrical stimulation of these nerves, and found to become shorter following an increase in the GPN-ph and/or SLN stimulus frequency. During simultaneous electrical stimulation of the GPN-ph and SLN (frequency: 5-10 Hz, intensity: 30 muA, duration: 1.0 ms for each), the onset latency of reflex swallowing became shorter than that for stimulation of each nerve independently. The present findings suggest that spatiotemporal summation of afferent signals from the GPN-ph and SLN results in an increase of motoneuronal activity in the medullary swallowing center, thus enhancing reflex swallowing.

Effects of taste solutions, carbonation, and cold stimulus on the power frequency content of swallowing submental surface electromyography.

This study explored the effects of 5 taste solutions (citric acid, sucrose, sodium chloride, caffeine, and sodium glutamate) versus water on the power frequency content of swallowing submental surface electromyography (sEMG). Healthy subjects were presented with 5 ml of each of 5 tastants and water. Data were collected in 3 trials of the 5 tastants and water by using submental sEMG, which was then subjected to spectral analysis. Sour and salt taste solutions increased the spectrum-integrated values of the total power components. The spectrum-integrated values of low-frequency power (below 10 Hz) in the salt taste trial significantly increased, whereas those of high-frequency power (above 10 Hz) in the sour taste trial tended to increase. Neither pleasantness nor intensity of taste was related to these changes. This study also explored the effects of carbonation and cold stimulus on the power frequency content of continuous swallowing sEMG for 60-ml solutions. Carbonation significantly increased the spectrum-integrated value of the total power components by significantly increasing the high-frequency content. Cold stimulus significantly decreased the low-frequency content. In summary, this study reveals that taste, carbonation, and cold stimulus have qualitatively different influences on the power frequency content of swallowing sEMG.

Leptin modulates the response to oleic acid in the pharynx.

Leptin released from the adipose tissues is known to inhibit obesity by regulating food intake. In this study, we investigated the effect of leptin on afferent nerve responses to fats and fatty acid in the pharyngolaryngeal region. The afferent nerve activities were recorded from the whole nerve bundle or pauci-fiber bundles of the pharyngeal branch of the glossopharyngeal nerve (GPN-ph) in Wistar normal and fatty rats. Oleic acid (long-chain fatty acid), mineral oil (nonfat oil) and safflower oil (vegetable oil; middle-chain fatty acid) were applied to the surface of pharyngolaryngeal mucous membrane. Oleic acid elicited vigorous stimulation of the GPN-ph activity in both normal and fatty rats but other oils had no significant effect on the activity. After intravenous administration of leptin (30 ng/kg, 1 ml), the response to oleic acid was significantly decreased in normal rats, whereas such a decrease was not found in fatty rats. These results are the first findings to indicate the existence of a suppressive mechanism of leptin on the response of the GPN-ph to fatty acid in normal rats, but that such a mechanism is lacking in fatty rats.

Response properties of the pharyngeal branch of the glossopharyngeal nerve for umami taste in mice and rats.

Many studies have reported the mechanism underlying umami taste. However, there are no investigations of responses to umami stimuli taste originating from chemoreceptors in the pharyngeal region. The pharyngeal branch of the glossopharyngeal nerve (GPN-ph) innervating the pharynx has unique responses to taste stimulation that differs from responses of the chorda tympani nerve and lingual branch of the glossopharyngeal nerve. Water evokes robust response, but NaCl solutions at physiological concentrations do not elicit responses. The present study was designed to examine umami taste (chemosensory) responses in the GPN-ph. Response characteristics to umami taste were compared between mice and rats. In mice, stimulation with compounds eliciting umami taste (0.1M monosodium L-glutamate (MSG), 0.01M inosine monophosphate (IMP) and the mixture of 0.1M MSG+0.01M IMP) evoked higher responses than application of distilled water (DW). However, synergistic response of a mixture of 0.1M MSG+0.01M IMP was not observed. In rats, there is no significant difference between the responses to umami taste (0.1M MSG, 0.01M IMP and the mixture of 0.1M MSG+0.01M IMP) and DW. Monopotassium glutamate (MPG) was used in rats to examine the contribution of the sodium component of MSG on the response. Stimulation with 0.1M MPG evoked a higher response when compared with responses to DW. The present results suggest that umami taste compounds are effective stimuli of the chemoreceptors in the pharynx of both mice and rats.

Nitric oxide modulates elicitation of reflex swallowing from the pharynx in rats.

The pharynx is very important for elicitation of reflex swallowing. The region of the pharynx is innervated by the pharyngeal branch of the glossopharyngeal nerve (GPN-ph). Nitric oxide (NO) plays an important role in various physiological functions. The purpose of this study is to investigate the contribution of NO to reflex swallowing evoked by electrical stimulation of the GPN-ph. Swallowing was evoked in urethane-anesthetized rats by application of repetitive electrical stimulation (10- to 20-microA amplitude, 10- to 20-Hz frequency, 1.0-ms duration) to the central cut end of the GPN-ph or superior laryngeal nerve. Swallowing was identified by electromyographic activity of the mylohyoid muscle. Latency to the first swallow and the interval between swallows were measured. Intravenous administration of N(G)-nitro-L-arginine (L-NNA, 0.6 mg/kg), a nonselective inhibitor of NO synthase (NOS), extremely prolonged latency to the first swallow and the interval between swallows evoked by the GPN-ph. Intraperitoneal administration of 7-nitroindazole (5.0 mg/kg), a selective inhibitor of neuronal NOS, significantly prolonged latency to the first swallow and the interval between swallows evoked by the GPN-ph. Administration of L-arginine (an NO donor, 500 mg/kg) and sodium nitroprusside (an NO releaser, 0.6 mg/kg) restored the suppression of swallowing induced by the NOS inhibitor. Superior laryngeal nerve-evoked swallowing was suppressed by administration of a higher dose of L-NNA (6.0 mg/kg). Swallowing evoked by water stimulation of the pharynx was also suppressed by L-NNA (0.6 mg/kg). These results suggest that NO plays an important role in signal processing for initiation of reflex swallowing from the pharynx.

Genesis of the decrement of intraluminal pressure in the UES during swallowing in rabbits.

The intraluminal pressure in the upper esophageal sphincter (UES) briefly decreases during swallowing. This decrement in pressure plays an important role in smooth transport of the ingested bolus from the pharynx to the esophagus. It is known that the decrement is caused by cessation of tonic activity of the cricopharyngeus (CP) muscle and also by elevation of the larynx. On the other hand, it is suspected that the recurrent laryngeal nerve (RLN) also contributes to the decrement, since our preliminary study showed for the first time that the decrement in UES pressure was much reduced after the RLN was sectioned. In the present study, we examined the genesis of the decrement of the UES pressure in anesthetized rabbits. When swallowing was elicited by repetitive electrical stimulation of the superior laryngeal nerve, the UES pressure briefly decreased and then abruptly increased. After bilateral sectioning of the RLN, the decrement of the pressure was significantly reduced, whereas the increment was little altered. Sectioning of the pharyngeal branch of the vagus nerve (X-ph) and the RLN mostly eliminated both the decrement and increment of the pressure, and abolished tonic and burst activities of the CP muscle. Electrical stimulation of peripheral end of the RLN decreased the pressure. These results indicate that the RLN and X-ph are involved in the decrement of the UES pressure during swallowing. The RLN generates the decrement by adducting the arytenoid cartilage and closing the glottis. The X-ph contributes to the decrement both by suppressing the tonic activity of the CP muscle and by regulating the laryngeal elevation.

A comparison of voluntary salt-intake behavior in Nax-gene deficient and wild-type mice with reference to peripheral taste inputs.

The Na(x) channel, a subfamily of voltage-gated sodium channels, is thought to be a specific sodium receptor in the central nervous system. Our previous study revealed that Na(x)-gene-deficient mice consumed excessive amounts of NaCl even under water-deprived conditions. In the present study, to investigate whether the peripheral taste inputs are involved in the abnormal intake of salt in Na(x)-deficient mice (homo), voluntary intake of various taste solutions in homo and wild-type mice (wild) was examined under non-deprived conditions. Homo showed a higher preference for 0.15 M NaCl solution than wild. Preference ratios for other basic tastants were identical between groups. Transection of the chorda tympani (CT) or the glossopharyngeal (GP) nerve had little effect on salt-intake behavior in homo and wild. Although combined transection of the superior laryngeal (SL) and GP nerves decreased NaCl intake in homo but not in wild, there were no differences in preference ratios for NaCl in homo before and after SL+GP transection. On the other hand, preference ratios for NaCl in wild tended to increase after combined SL and GP transection. Consequently, preference ratios for NaCl after SL+GP transection were no different between homo and wild. While electrophysiological responses of the CT and the GP to various taste solutions were indistinguishable between homo and wild, those of the SL to NaCl in homo were smaller than those in wild only at lower concentrations (0.01 and 0.03 M). Thus, chemosensory inputs from the oro-pharyngeal regions had little effect on abnormal salt intake in homo, if any. From these results, it is suggested that the higher preference for NaCl in homo is mainly due to the lack of Na(x) channels in the central nervous system.

Role of the pharyngeal branch of the vagus nerve in laryngeal elevation and UES pressure during swallowing in rabbits.

Elevation of the larynx during swallowing plays an important role in protecting the laryngeal inlet and in the opening of the upper esophageal sphincter (UES). The thyrohyoid (TH) muscle is the most important muscle for laryngeal elevation, and it is thought to be innervated by the thyrohyoid branch. However, in preliminary studies we found that laryngeal elevation was severely disturbed after sectioning of the pharyngeal branch of the vagus nerve (X-ph). In the present study, we examined the role of the X-ph in laryngeal elevation and the contribution of this nerve to UES pressure. Ten male rabbits under anesthesia were used. Sectioning of the X-ph not only abolished the electromyographic activities of the TH and cricopharyngeus (CP) muscles, it also greatly reduced the maximal value of laryngeal elevation during swallowing. On the other hand, sectioning of the hypoglossal nerve, which contains the thyrohyoid branch, produced no appreciable change in the electromyographic activity of either muscle and it reduced the maximal value of the elevation only slightly. These results indicate that the X-ph innervates the TH and CP muscles and suggest that the X-ph plays an important role in elevating the larynx and in regulating the UES pressure in rabbits.

Sour taste stimulation facilitates reflex swallowing from the pharynx and larynx in the rat.

Chemical stimulation of the pharynx and larynx is effective in eliciting reflex swallowing. A sour taste bolus facilitates the onset of swallowing in patients with neurogenic dysphagia, but the mechanism of the facilitation has not been clarified. We investigated the effect of sour solutions on the elicitation of reflex swallowing in anesthetized rats. The main ducts of salivary glands were ligated to avoid the effect of saliva. A small amount of water, sour solutions, and other taste solutions were applied to the mucosa of the pharyngolaryngeal region. Acetic acid and citric acid, which provide a sour taste, had a stronger effect on evoking reflex swallowing as compared with other taste solutions. The effectiveness of these acids increased with increasing concentrations. We also examined the contribution of the superior laryngeal nerve (SLN) and the pharyngeal branch of the glossopharyngeal nerve (GPNph) to reflex swallowing. Acetic acid was greatly effective in evoking swallowing in both the region innervated by the SLN and the GPNph. On the other hand, water was effective in the SLN region but only slightly effective in the GPNph region. The results indicate that stimulation of the pharyngolaryngeal region with sour solutions facilitates reflex swallowing, suggesting that the facilitation may be due to increases of sensory inputs via the SLN and GPNph.

Pharyngeal branch of the glossopharyngeal nerve plays a major role in reflex swallowing from the pharynx.

Mechanical stimulation of the pharyngeal areas readily elicits reflex swallowing. However, it is much more difficult for electrical stimulation of the glossopharyngeal nerve (GPN) to evoke reflex swallowing than it is for stimulation of the superior laryngeal nerve (SLN) to do so. These paradoxical findings remain unexplained; hence, the main purpose of this study was to explain this contradiction by using a urethane-anesthetized rat. Mechanical stimulation easily elicited reflex swallowing from the pharynx. The posterior pillars, posterior pharyngeal wall, and the soft palate of the rat were extremely reflexogenic areas for swallowing. Sectioning the pharyngeal branch of the GPN (GPN-ph), however, eliminated the swallowing reflex from these areas. In contrast, sectioning the lingual branch of the GPN had no effect on the elicitation of swallowing. Electrical stimulation of the GPN-ph and SLN elicited sequentially occurring swallows. The relationship between stimulus frequency and the latency of swallowing for the GPN-ph was approximately the same as that for the SLN. These results indicate that the GPN-ph plays a major role in the initiation of reflex swallowing from the pharynx in rats.