Morphological Features of the Glossopharyngeal Nerve in the Peripharyngeal Space, the Oropharynx, and the Tongue.

The glossopharyngeal nerve comprises sensory, motor and parasympathetic fibers, and its problem results in several disorders. This study investigated the glossopharyngeal nerve to elucidate the characteristics of its extracranial course and branching pattern. The nerve and adjacent structures were gross anatomically examined in 32 cadavers. The glossopharyngeal nerve descended from the jugular foramen in the peripharyngeal space. It dodged between the carotid arteries and the internal jugular vein and distributed the carotid and pharyngeal branches that formed the plexus with the branches of the vagus and sympathetic nerves. The glossopharyngeal nerve curved anteriorly around the stylopharyngeus and supplied it and the glossopharyngeus. However, it occasionally disappeared because it penetrated the stylopharyngeus. The nerve passed medially to the stylohyoid ligament to enter the oropharynx, with its entry located medially to the facial artery. It appeared anteriorly to the stylopharyngeus and the palatopharyngeus and inferiorly to the palatine tonsil in the oropharynx. Its appearance was obscured beneath the tonsil and, sometimes, beneath the longitudinal muscles. The nerve distributed the branches to the palatine tonsil, which formed a plexus with those that pierced the glossopharyngeus from the outside. At the root of the tongue, the nerve ramified into the posterior branches to the epiglottic vallecula, the medial ones the lingual tonsil and the vallate papillae and the anterior ones the vallate and foliate papillae. This study suggests that, occasionally, the detection of the glossopharyngeal nerve is challenging, and its association with the pharyngeal muscles and the facial artery can facilitate its localization. Anat Rec, 302:630-638, 2019. © 2018 Wiley Periodicals, Inc.

Characterization of sheep (Ovis aries) palatine tonsil innervation.

Palatine tonsils (PTs), together with ileal Peyer's patches, rank among the first colonization sites for infectious prions. After replicating in these lymphoid tissues, prions undertake the process of "neuroinvasion," which is likely mediated by the peripheral nerves connecting lymphoid tissues to the central nervous system (CNS). To study the connections between the tonsils and the CNS, we injected fluorescent tracers into the PTs of lambs; the highest number of Fast Blue (FB)-labeled neurons was found in cranial cervical ganglia (CCG), whereas a progressively decreasing number of cells were detected in proximal glossopharyngeal, proximal vagal, trigeminal, pterygopalatine, and cervicothoracic ganglia. Immunohistochemistry was carried out on tonsil and ganglia cryosections. Immunoreactivity (IR) for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP), substance P (SP), and calcium-binding protein S100 (S100), was observed in the fibers around and within PT lymphoid nodules. In the trigeminal, proximal glossopharyngeal and vagal ganglia the retrogradely-labeled neurons showed nNOS-, SP- and CGRP-IR. In all ganglia some retrogradely-labeled neurons showed nNOS-, SP- and CGRP-IR co-localization. It is worth noting that only 66+/-19% and 75+/-13% of retrogradely-labeled neurons in CCG showed TH- and DBH-IR, respectively. The present results allow us to attribute PT innervation mainly to the sympathetic component and to the glossopharyngeal, vagal and trigeminal cranial nerves. Furthermore, these data also provide a plausible anatomic route through which infectious agents, such as prions, may access the CNS, i.e. by traveling along several cranial and sympathetic nerves, as well as by migration via glial cells.

Modified infiltration technique in tonsillectomy: expanded case report of 25 children.

OBJECTIVE: To introduce a modified infiltration technique of anesthetic mixture in order to reduce post-tonsillectomy pain based on histo-anatomic observations and tonsil's innervation detection. DESIGN: Histo-anatomic, expanded case report. SETTING: Tertiary care facility in Beirut, Lebanon. PATIENTS: One hundred and seven patients who underwent tonsillectomy allocated in three groups. INTERVENTIONS: Histo-anatomic observations were studied in 62 patients (group I). Nerve-stimulator detection was performed in group II (20 children). An expanded case report of 25 children (group III) was conducted using a modified infiltration technique based on the findings of the histo-anatomic observations and nerve detection. OUTCOME MEASURES: Post-operative pain at 0, 6, 12h and once daily for the 10-day follow-up period, hemodynamic stability, hospital stay, patient satisfaction and analgesics consumption were assessed. RESULTS: The nerve-stimulator confirmed the histo-anatomic findings by strong contractions of the superior constrictor muscle, soft palate and uvula when the needle is mainly in the middle part of the peritonsillar area where the glossopharyngeal nerve branches predominate. No visual analogue scale median exceeded 1 for any child at any predetermined time interval, only three children (12%) required opoiods during the follow-up period. All children (100%) were discharged the same day, only 4% of parents were unsatisfied. Hemodynamic stability was maintained during pre- and post-operation. CONCLUSION: This modified technique with minimal volume of anesthetic mixture seems to reduce post-operative pain in tonsillectomy patients; a randomized double-blinded prospective study was designed based on the findings in this initial series of children.

Upper airway muscle inflammation and denervation changes in obstructive sleep apnea.

Inflammatory cell infiltration and afferent neuropathy have been shown in the upper airway (UA) mucosa of subjects with obstructive sleep apnea (OSA). We hypothesized that inflammatory and denervation changes also involve the muscular layer of the pharynx in OSA. Morphometric analysis was performed on UA tissue from nonsnoring control subjects (n = 7) and patients with OSA (n = 11) following palatal surgery. As compared with control subjects, inflammatory cells were increased in the muscular layer of patients with OSA, with CD4+ and activated CD25+ T cells (both increased approximately threefold) predominating. Inflammation was also present in UA mucosa, but with a different pattern consisting of CD8+ (2.8-fold increase) and activated CD25+ (3.2-fold increase) T cell predominance. As ascertained by immunoreactivity for the panneuronal marker PGP9.5, there was a dramatic (5.7-fold) increase in intramuscular nerve fibers in OSA patients compared with control subjects, as well as direct evidence of denervation based on positive immunostaining of the muscle fiber sarcolemmal membrane for the neural cell adhesion molecule in patients with OSA. These data suggest that inflammatory cell infiltration and denervation changes affect not only the mucosa, but also the UA muscle of patients with OSA. This may have important implications for the ability to generate adequate muscular dilating forces during sleep.

Adrenergic and acetylcholinesterase-positive innervation of palatine tonsils in mammals.

Innervation of human, feline and rabbit palatine tonsils was investigated. Adrenergic nerve components were visualized by formaldehyde-induced fluorescence of catecholamines and 5-HT, or by glyoxylic acid fluorescence, whereas acetylcholinesterase (AChE)-positive nerve structures were demonstrated by the direct thiocholine method. The largest density of adrenergic and AChE-positive nerve profiles was found in the adventitia of arterial branches in the fibrous capsula and septa, mainly in the form of periarterial nerve plexuses of different density. Fine nerve fibres lined the wall of small arteries which penetrated into extrafollicular lymphoid tissue and marginal layers of follicles. It is concluded that there are significant species-specific differences related to density, nature and topographic relations of adrenergic and AChE-positive nerve fibres in the various structural parts of palatine tonsils.

The trigeminal nerve. Part III: The maxillary division.

The maxillary nerve gives sensory innervation to all structures in and around the maxillary bone and the midfacial region including the skin of the midfacial regions, the lower eyelid, side of nose, and upper lip; the mucous membrane of the nasopharynx, maxillary sinus, soft palate, palatine tonsil, roof of the mouth, the maxillary gingivae, and maxillary teeth. This vast and complex division of the trigeminal nerve is intimately associated with many sources of orofacial pain, often mimicking maxillary sinus and/or temporomandibular joint involvement. For those who choose to treat patients suffering with orofacial pain and temporomandibular disorders, knowledge of this nerve must be second nature. Just providing the difficult services of a general dental practice should be stimulus enough to understand this trigeminal division, but if one hopes to correctly diagnose and treat orofacial pain disorders, dedication to understanding this nerve cannot be overstated. In this, the third of a four part series of articles concerning the trigeminal nerve, the second or maxillary division will be described and discussed in detail.

Tonsillar pain mimicking glossopharyngeal neuralgia as a complication of vagus nerve stimulation: case report.

An adolescent girl presented with severe, lancinating tonsillar pain exacerbated by swallowing 6 weeks after initiation of left vagus nerve stimulation for intractable epilepsy. Her symptoms mimicked those seen in glossopharyngeal neuralgia and were relieved by temporary cessation of stimulation. Gradual reinstitution of therapy with alteration in stimulus parameters resulted in improved seizure control as well as cessation of pain symptoms. Direct stimulation of the vagus nerve may result in vagoglossopharyngeal neuralgia, which, in this case, was amenable to stimulus modification.

Convergence of afferent inputs from the chorda tympani, lingual-tonsillar and pharyngeal branches of the glossopharyngeal nerve, and superior laryngeal nerve on the neurons in the insular cortex in rats.

The responses of single neurons in the insular cortex to electrical stimulation of the chorda tympani (CT), lingual-tonsillar branch of the glossopharyngeal (LT-IXth) nerve, pharyngeal branch of the glossopharyngeal (PH-IXth) nerve, and superior laryngeal (SL) nerve were recorded in anaesthetized and paralyzed rats. Ninety-four neurons responding to stimulation of at least one of the four nerves were identified from the insular cortex. Most of the neurons were located in the posterior portion of the insular cortex; the mean location was 0.8 mm anterior to the anterior edge of the joining of the anterior commissure (AC) and was 1.4 mm dorsal to the rhinal fissure (RF). Of the 94 neurons, 84 (89%) received convergent inputs from two or more nerves, and the remaining 10 (11%) received inputs from one nerve. The neurons responding to the CT stimulation were distributed more anteriorly than those responding to other three nerves in the anterior-posterior dimension. Our results indicate that the neurons recorded mainly from the posterior portion of the insular cortex receive convergent inputs from the oropharyngolaryngeal regions.

[Clinico-pathogenetic variants of neurocirculatory dystonia in patients with a chronic focal infection of the upper respiratory tract]. / Kliniko-patogeneticheskie varianty neirotsirkuliatornoi distonii u bol'nykh s khronicheskoi ochagovoi infektsiei verkhnikh dykhatel'nykh putei.

Particular features have been studied of clinical course of neurocirculatory dystonia (NCD) in 604 patients with chronic focal infection (ChFI) of upper respiratory tract. Comprehensive paraclinical examination of patients included the analysis of actual psychoemotional state and certain psychophysiological parameters such as time for simple and complex sensomotor reaction, memory, attention; status of vegetative regulation (tone, reactivity, vegetative security of activity) and its neurohumoral and metabolic provision; adaptive potentialities of vegetative, neuroendocrine and cardiorespiratory systems to mental, psychoemotional and physical demands; tonsillocardiac and palatocardiac reflexes according to an original methodology. Described for the first time are two clinico-pathogenetic variants ("peripheral" and "central") of NCD in patients with ChFI, which can be distinguished by severity of clinical manifestations, as well as by degree of disturbances in homeostasis and adaptation in vegetative, neurohumoral, somatic and psychoemotional spheres. Practical significance of the aforementioned variants consists in feasibility of employing pathogenetic approaches to the treatment of NCD and ChFI patients. Pathogenetic method of treatment of patients with NCD and ChFI is discussed.

[Neurocirculatory dystonia in patients with a chronic focal infection: the mechanisms of its formation and development]. / Neirotsirkuliatornaia distoniia u bol'nykh khronicheskoi ochagovoi infektsiei: mekhanizmy formirovaniia i razvitiia.

Clinical manifestations of neurocirculatory asthenia (NA) were analyzed in 604 patients with associated chronic focal infection. It is shown that the latter infection produces negative effects on clinical symptoms of NA, its course, temporary disability and effectiveness of treatment. Vegetative reactivity and vegetative activity in NA patients with the infection were affected to a greater degree than in NA patients without the focal infection. The role of afferent impulses from the nasopharynx reflexogenic zone in the genesis of clinical specificity and vegetative regulation defects in NA patients is discussed.

A histofluorescent study of sympathetic innervation of human palatine tonsils.

The glyoxylic catecholaminergic histofluorescence method was employed on human palatine tonsil specimens in order to study the sympathetic innervation present. One percent neutral red was used as a counterstain. Abundant sympathetic fibers were demonstrable around the blood vessels of the medulla and capsule. However, few sympathetic fibers were found around the vessels of the subepithelial connective tissue and interfollicular septa. In the areas of the follicle and extrafollicle where B and T lymphocytes were located, sympathetic fibers were not found. These findings indicate that if sympathetic innervation can affect T and B cells, it will do so indirectly. Results also show that there is a higher norepinephrine content in focally infected tonsils that is not due to hyperactivity of the sympathetic nerve, but may be due to other mechanisms. Finally surgical dissection at the capsule during tonsillectomy will reduce bleeding, perhaps because vessels there have an abundant sympathetic innervation that leads to good vessel contraction.

The effect of pre-incisional infiltration of tonsils with bupivacaine on the pain following tonsillectomy under general anesthesia.

The aim of the present study was to test the hypothesis that blockade of nociceptive input with bupivacaine during tonsillectomy can decrease pain beyond the immediate postoperative period. Fourteen patients between the ages of 6 and 18 years scheduled for tonsillectomy (with or without adenoidectomy) were randomly divided into two groups. The patients of both groups received 0.006 mg/kg atropine and anesthesia was induced by inhalation of halothane. Atracurium 0.5 mg/kg was used for myorelaxation. After oral intubation anesthesia was maintained with isoflurane plus nitrous oxide 67% in oxygen. In the bupivacaine group, 5 min before incision the tonsillar fossae were infiltrated with 0.25% bupivacaine with epinephrine (1 : 200,000). In the control group, the tonsillar fossae were infiltrated with normal saline with epinephrine (1 : 200,000). All patients received morphine 0.07 mg/kg (in the recovery room) and oral elixir with codeine 0.05 mg/kg plus acetaminophen 5 mg/kg every 4 h. Pain assessments were made using the visual analog (100 mm scale) self-rating method. Two types of pain were assessed: constant incisional pain and pain caused by drinking 100 ml of water. In the bupivacaine group, the constant pain score on the second day after surgery was 19 +/- 6 compared to 74 +/- 8 in the saline group (P less than 0.0002). By the 4-5th day after surgery almost no constant pain occurred in the bupivacaine group, but the pain score remained at the 40-60 level in the saline group. The difference in pain intensity on swallowing between the bupivacaine and saline groups was present even on the 10th postoperative day (1 +/- 1 vs. 14 +/- 5, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular anatomy of the neuro-immune connection.

Light microscopic immunohistochemistry was employed to elucidate and compare the presence, distribution, and coexistence of various peptides, neuroendocrine markers and enzymes of the catecholamine pathway in nerves supplying lymphoid tissues in a variety of mammalian species. All lymphoid organs and tissues receive innervation by fibers containing dopamine-beta-hydroxylase and/or tyrosine hydroxylase, neural markers like protein gene product 9.5, synaptophysin and neurofilament and a varied spectrum of peptides. The prominent peptides were tachykinins (substance P, neurokinin A), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide/peptide histidine isoleucine (VIP/PHI). Opioid innervation was variable. Double immunofluorescence revealed coexistence of tachykinins and CGRP and of tyrosine hydroxylase and NPY. A minor proportion of fibers showed coexistence of NPY and tachykinins and of VIP/PHI and tachykinins. The possible importance of the complex peptidergic innervation of lymphoid tissues in inflammation, allergy, inflammatory pain and psycho-neuro-immuno-endocrine network function is discussed. A special immunomodulatory role of the sensory neurons is suggested.

The neuroimmune connection in human tonsils.

The present light microscopic immunohistochemical study evaluates the distribution of peptidergic nerve fibers in human tonsil and describes their spatial relationship with specific cells of the immune system. Further, using a panneural marker protein gene product (PGP) 9.5, a qualitative evaluation of the density of specific peptidergic innervation of the human tonsil was performed. Nerve fibers staining for tachykinins, calcitonin gene-related peptide, neuropeptide Y, or vasoactive intestinal polypeptide/peptide histidine isoleucine showed characteristic distribution patterns, but constituted only a minor subfraction of the PGP 9.5-stained fiber population. Both peptide- and PGP 9.5-immunopositive fibers predominantly supplied the vasculature; nonvascular areas were less densely innervated. Double staining for surface antigens thought to be associated with subsets of lymphoid cells, i.e., T-cells, B-cells, granulocytes, and macrophages, and for peptides or PGP 9.5 revealed close proximity of characteristic subpopulations of neurochemically defined nerve fibers and the various immune cells. The presence of peptidergic nerve fibers among T-cells was more prevalent than peptidergic nerve fibers adjacent to macrophages. Few positively stained nerve fibers resided in B-cell compartments. Neuro-B-cell interrelations were extremely infrequent. Neuroimmune connections were restricted to paravascular, subepithelial, and interfollicular regions, while germinal centers were devoid of nerve supply. The results are compatible with the view that peptides, being present in small-diameter nerve fibers, could exert an indirect immunoregulatory role by influencing vascular tone and/or permeability. In quantitative terms, a direct neuroimmunomodulatory action of endogenous neurally derived peptides appears to be of minor importance, because nonvascular neuroimmune circuits were found infrequently and were regionally restricted. However, we cannot be sure that all fibers were stained. The functional state of the peptidergic and nonpeptidergic innervation of the human palatine tonsil may be of physiological and pathophysiological significance within the psycho-neuro-immuno-endocrine network. The peptide-coded neuroimmune link may play a role in tonsillar pain.

Immunolocalization of tyrosine hydroxylase and vasoactive intestinal polypeptide in nerve fibers innervating human palatine tonsil and paratonsillar glands.

The presence of tyrosine hydroxylase (TH) and vasoactive intestinal polypeptide (VIP) in the nerve fibers of the human palatine tonsil and paratonsillar secretory glands is reported. By immunohistochemistry TH-immunoreactive nerves and those immunoreactive to VIP were localized to the tonsil, in particular, the tonsillar vessel wall, extranodular lymphoid tissue and lymph nodule, and to the acinar basal surface of the paratonsillar glands. In the lymph nodule, immunoreactive varicose nerve profiles were observed inside the marginal zone. The germinal center was devoid of immunoreactive fibers.