To evaluate the mechanisms underlying orofacial motor dysfunction associated with trigeminal nerve injury, we studied the astroglial cell activation following chronic constriction injury (CCI) of the infraorbital nerve (ION) immunohistochemically, nocifensive behavior in ION-CCI rats, and the effect of the glutamine synthase (GS) blocker methionine sulfoximine (MSO) on the jaw-opening reflex (JOR), and also studied whether glutamate-glutamine shuttle mechanism is involved in orofacial motor dysfunction. GFAP-immunoreactive (IR) cells were observed in the trigeminal motor nucleus (motV) 3 and 14 days after ION-CCI, and the nocifensive behavior and JOR amplitude were also strongly enhanced at these times. The number of GS- and GFAP-IR cells was also significantly higher in ION-CCI rats on day 7. The amplitude and duration of the JOR were strongly suppressed after MSO microinjection (m.i.) into the motV compared with that before MSO administration in ION-CCI rats. After MSO administration, the JOR amplitude was strongly suppressed, and the duration of the JOR was shortened. Forty minutes after m.i. of glutamine, the JOR amplitude was gradually returned to the control level and the strongest attenuation of the suppressive effect of MSO was observed at 180 min after glutamine m.i. In addition, glutamine also attenuated the MSO effect on the JOR duration, and the JOR duration was extended and returned to the control level thereafter. The present findings suggest that astroglial glutamate-glutamine shuttle in the motV is involved in the modulation of excitability of the trigeminal motoneurons affecting the enhancement of various jaw reflexes associated with trigeminal nerve injury.
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.
We report a case of adenocarcinoma of the minor duodenal papilla, a rare type of duodenal neoplasm. A 76-year-old man with a history of surgery for rectal cancer and gastric cancer was referred to us after a follow-up upper gastrointestinal endoscopy revealed an abnormal elevation in the minor duodenal papilla. The pathological diagnosis of a biopsy specimen was adenocarcinoma. Preoperative examination of other organs revealed a tumor in the ascending colon, which was also identified as adenocarcinoma. We performed synchronous pancreatoduodenectomy and ileocecal resection with lymph node dissection. Histopathological examination of the resected specimen revealed that the papilla tumor arose from the duodenal mucosa and infiltrated the submucosa of the duodenal wall, but not the pancreatic parenchyma. Based on these findings, we diagnosed primary adenocarcinoma of the minor duodenal papilla. To our knowledge, this is only the sixth such case reported in the English-language literature, and we review all six cases after this case report.
The swallowing reflex is centrally programmed by the lower brain stem, the so-called swallowing central pattern generator (CPG), and once the reflex is initiated, many muscles in the oral, pharyngeal, laryngeal, and esophageal regions are systematically activated. The mylohyoid (MH) muscle has been considered to be a "leading muscle" according to previous studies, but the functional role of the digastric (DIG) muscle in the swallowing reflex remains unclear. In the present study, therefore, the activities of single units of MH and DIG neurons were recorded extracellularly, and the functional involvement of these neurons in the swallowing reflex was investigated. The experiments were carried out on eight adult male Japanese white rabbits anesthetized with urethane. To identify DIG and MH neurons, the peripheral nerve (either DIG or MH) was stimulated to evoke action potentials of single motoneurons. Motoneurons were identified as such if they either (1) responded to antidromic nerve stimulation of DIG or MH in an all-or-none manner at threshold intensities and (2) followed stimulation frequencies of up to 0.5 kHz. As a result, all 11 MH neurons recorded were synchronously activated during the swallowing reflex, while there was no activity in any of the 7 DIG neurons recorded during the swallowing reflex. All neurons were anatomically localized ventromedially at the level of the caudal portion of the trigeminal motor nucleus, and there were no differences between the MH and DIG neuron sites. The present results strongly suggest that at least in the rabbit, DIG motoneurons are not tightly controlled by the swallowing CPG and, hence, the DIG muscle is less involved in the swallowing reflex.
The present study aimed to examine whether the jaw-opening reflex (JOR) is modulated during swallowing, and if so, to compare the modulation between the low- and high-threshold afferent-evoked reflex responses. Experiments were carried out on 11 anesthetized rabbits. The inferior alveolar nerve was stimulated to evoke the JOR in the digastric muscle. The stimulus intensity was either 1.5 (low threshold) or 4.0 (high threshold) times the threshold for eliciting the JOR. As a conditioning stimulation, the superior laryngeal nerve (SLN) was repetitively stimulated to evoke the swallowing reflex. The stimulus intensity ranged from 0.6 to 8.0 times the threshold to evoke the swallowing reflex during SLN stimulation over 20s. Electromyographic (EMG) activities of the digastric and mylohyoid muscles were recorded, and the peak-to-peak EMG amplitude of the digastric muscle was measured and compared with and without SLN stimulation, as well as with and without swallowing. Comparisons were also made between low- and high-threshold afferent-evoked JORs. The JOR was strongly suppressed during SLN stimulation. The degree of suppression increased and the latency for the JOR was delayed when the stimulus current applied to the SLN was increased. Such modulation was apparent when the low-threshold afferent-evoked JOR was recorded. Effects of motor outputs of swallowing events and those of single-pulse stimulation of SLN on the inhibition of the JOR were not noted. These results suggest that the JOR evoked by both the low- and high-threshold afferents was inhibited during laryngeal sensory input and following swallowing, probably to prevent opposing jaw movements evoked by oral sensory input during swallowing.
Swallowing involves several motor processes such as bolus formation and intraoral transport of a food bolus (oral stage) and a series of visceral events that occur in a relatively fixed timed sequence but are to some degree modifiable (pharyngeal stage or swallow reflex). Reflecting the progressive aging of society, patients with swallowing disorders (i.e., dysphagia) are increasing. Therefore, there is expanding social demand for the development of better rehabilitation treatment of dysphagic patients. To date, many dysphagia diets have been developed and are available commercially to help bring back the pleasure of mealtimes to dysphagia patients. Texture modification of food to make the food bolus easier to swallow with less risk of aspiration is one of the important elements in dysphagia diets from the viewpoint of safety assurance. However, for the further development of dysphagia diets, new attempts based on new concepts are needed. One of the possible approaches is to develop dysphagia diets that facilitate swallow initiation. For this approach, an understanding of the mechanisms of swallow initiation and identification of factors that facilitate or suppress swallow initiation are important. In this review, we first summarize the neural mechanisms of swallowing and effects of taste and other inputs on swallow initiation based on data mainly obtained from experimental animals. Then we introduce a recently established technique for eliciting swallowing using electrical stimulation in humans and our ongoing studies using this technique.
The relationships between jaw-closing muscle spindle unit discharge and the hardness of foods were evaluated during chewing in awake rabbits. Spindle unit discharges recorded from the left mesencephalic trigeminal nucleus were correlated with the simultaneous recording of jaw movements and electromyographic (EMG) activities of the left masseter (jaw-closing) muscle during chewing soft and hard foods. A chewing cycle was divided into the fast-closing (FC), slow-closing (SC) and opening (OP) phases according to jaw movements. The chewing was classified as ipsilateral and contralateral chewing according to ipsilateral and contralateral to the recording side of the neuron, respectively. Spindle unit discharge was significantly higher during the FC and SC phases of the hard food than the soft food during both ipsilateral and contralateral chewing. The discharge was observed to be higher when the masseter muscle activity was higher. A comparison between the chewing sides reveals that the discharge was significantly higher during the slow-closing phase of ipsilateral chewing than contralateral chewing. From the above findings, the relationship of the spindle unit discharge with the hardness of foods was observed. Moreover, this relationship exists even when an animal chews food on the contralateral side suggesting the significance of the muscle spindle information for smooth chewing. In addition, the phase dependent difference of the spindle unit discharge between chewing sides suggests the distinct roles of the spindle information on the chewing and non-chewing sides.
The present study aimed to determine if sensory inputs from the intraoral mechanoreceptors similarly contributed to regulating the activity of the jaw-opening muscles throughout the masticatory sequence. We also aimed to determine if sensory inputs from the chewing and non-chewing sides equally regulated the activity of the jaw-opening muscles. Electromyographic (EMG) activities of jaw muscles (digastric and masseter) and jaw movements were recorded in awake rabbits. The entire masticatory sequence was divided into preparatory, rhythmic-chewing and preswallow periods, based on jaw muscles activity and jaw movements. The jaw-opening reflex (JOR) was evoked by unilateral low-intensity stimulation of the inferior alveolar nerve (IAN) on either the chewing or non-chewing side. Amplitude of the JOR was assessed by measuring peak-to-peak EMG activity in the digastric muscle, and was compared among the masticatory periods and between the chewing and non-chewing sides. The JOR was strongly suppressed during the jaw-closing phase in the rhythmic-chewing and preswallow periods, but this effect was transiently attenuated during the late part of the jaw-opening phase in these periods. However, modulation of the JOR varied from strong suppression to weak facilitation during the preparatory period. The patterns of JOR modulation were similar on the chewing and non-chewing sides in all masticatory periods. The results suggest that the sensory inputs from the intraoral mechanoreceptors regulate the activity of the jaw-opening muscles differently during the preparatory period compared with the other masticatory periods. Sensory inputs from both the chewing and non-chewing sides similarly regulate the activity of the jaw-opening muscles.
From the standpoint of dental medicine, denture wearing is considered to improve chewing ability, chewing comfort, and quality of life in elderly individuals. We attempted to clarify the effects of prosthodontic treatment on activation of the dorsal prefrontal cortex, which is involved in higher cognitive functions.
Cannabinoids have been reported to be involved in affecting various biological functions through binding with cannabinoid receptors type 1 (CB1) and 2 (CB2). The present study was designed to investigate whether swallowing, an essential component of feeding behavior, is modulated after the administration of cannabinoid. The swallowing reflex evoked by the repetitive electrical stimulation of the superior laryngeal nerve in rats was recorded before and after the administration of the cannabinoid receptor agonist, WIN 55-212-2 (WIN), with or without CB1 or CB2 antagonist. The onset latency of the first swallow and the time intervals between swallows were analyzed. The onset latency and the intervals between swallows were shorter after the intravenous administration of WIN, and the strength of effect of WIN was dose-dependent. Although the intravenous administration of CB1 antagonist prior to intravenous administration of WIN blocked the effect of WIN, the administration of CB2 antagonist did not block the effect of WIN. The microinjection of the CB1 receptor antagonist directly into the nucleus tractus solitarius (NTS) prior to intravenous administration of WIN also blocked the effect of WIN. Immunofluorescence histochemistry was conducted to assess the co-localization of CB1 receptor immunoreactivity to glutamic acid decarboxylase 67 (GAD67) or glutamate in the NTS. CB1 receptor was co-localized more with GAD67 than glutamate in the NTS. These findings suggest that cannabinoids facilitate the swallowing reflex via CB1 receptors. Cannabinoids may attenuate the tonic inhibitory effect of GABA (gamma-aminobuteric acid) neurons in the central pattern generator for swallowing.
Increased expression of the transient receptor potential vanilloid 1 (TRPV1) channels, following nerve injury, may facilitate the entry of QX-314 into nociceptive neurons in order to achieve effective and selective pain relief. In this study we hypothesized that the level of QX-314/capsaicin (QX-CAP)--induced blockade of nocifensive behavior could be used as an indirect in-vivo measurement of functional expression of TRPV1 channels. We used the QX-CAP combination to monitor the functional expression of TRPV1 in regenerated neurons after inferior alveolar nerve (IAN) transection in rats. We evaluated the effect of this combination on pain threshold at different time points after IAN transection by analyzing the escape thresholds to mechanical stimulation of lateral mental skin. At 2 weeks after IAN transection, there was no QX-CAP mediated block of mechanical hyperalgesia, implying that there was no functional expression of TRPV1 channels. These results were confirmed immunohistochemically by staining of regenerated trigeminal ganglion (TG) neurons. This suggests that TRPV1 channel expression is an essential necessity for the QX-CAP mediated blockade. Furthermore, we show that 3 and 4 weeks after IAN transection, application of QX-CAP produced a gradual increase in escape threshold, which paralleled the increased levels of TRPV1 channels that were detected in regenerated TG neurons. Immunohistochemical analysis also revealed that non-myelinated neurons regenerated slowly compared to myelinated neurons following IAN transection. We also show that TRPV1 expression shifted towards myelinated neurons. Our findings suggest that nerve injury modulates the TRPV1 expression pattern in regenerated neurons and that the effectiveness of QX-CAP induced blockade depends on the availability of functional TRPV1 receptors in regenerated neurons. The results of this study also suggest that the QX-CAP based approach can be used as a new behavioral tool to detect dynamic changes in TRPV1 expression, in various pathological conditions.
To determine the effects of inferior alveolar nerve transection (IAN-X) on masticatory movements in freely moving rats and to test if microglial cells in the trigeminal principal sensory nucleus (prV) or motor nucleus (motV) may be involved in modulation of mastication, the effects of microglial cell inhibitor minocycline (MC) on masticatory jaw movements, microglia (Iba1) immunohistochemistry and the masticatory jaw movements and related masticatory muscle EMG activities were studied in IAN-X rats.
We designed an electrical stimulation system to safely and reliably evoke the swallowing reflex in awake humans, and then examined the neural control of reflex swallowing initiated by oropharyngeal stimulation. A custom-made electrode connected to a flexible stainless-steel coil spring tube was introduced into the pharyngeal region through the nasal cavity and placed against the posterior wall of the oropharynx. Surface electrodes placed over the suprahyoid muscles recorded the electromyogram during swallowing. Swallowing reflexes were induced several times by 30 s of repetitive electrical pulse stimulation (intensity: 0.2-1.2 mA, frequency: 10-70 Hz, pulse duration: 1.0 ms). The onset latency of the swallowing reflex was measured over the 10-70 Hz frequency range. In addition, the two time intervals between the first three swallows were measured. The onset latency of the swallowing reflex became shorter as the stimulus frequency increased up to ?30 Hz. Once the frequency exceeded 30 Hz, there was no further reduction in the latency. This finding was consistent with those of previous studies in anesthetized animals. The time intervals between successive swallowing reflexes did not change with increased stimulus frequencies. Furthermore, prolonged stimulation often failed to elicit multiple swallowing reflexes. The frequency dependence of onset latency suggests that temporal summation of pharyngeal afferents is required to activate the medullary swallowing center. This reliable stimulation method may help in rehabilitation of dysphagic patients without causing aspiration.
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