Trigeminal Root Entry Zone Research Articles

A pontine-specific axonal niche supports de novo gliomagenesis.

The trigeminal root entry zone underlies pontine-specific gliomagenesis driven by H3.1K27M and its co-occurring mutations.

Trigeminal Neuralgia and Associated Hydrocephalus: Not a Mere Incidental Finding? A Case Report and Literature Review

BACKGROUND: Trigeminal neuralgia (TN) is most commonly related to vascular compression of the trigeminal root entry zone into the brainstem. Secondary causes of compression are much less common. TN as a sole manifestation of hydrocephalus has rarely been reported in the literature. CASE REPORT: We describe a young woman with medically resistant TN, who was discovered to have a tectal plate glioma causing secondary obstructive hydrocephalus. In addition, she had an incidental finding of ecchordosis physaliphora. Cerebrospinal fluid diversion by an endoscopic third ventriculostomy resulted in TN resolution. CONCLUSION: Hydrocephalus is a rare diagnosis to consider as a secondary cause for TN. Since the literature on this is sparse, it can be only suggested that in very select cases, treating the hydrocephalus may also treat the TN. Additional studies and reports are required. KEY WORDS: Trigeminal neuralgia, hydrocephalus, ecchordosis physaliphora, tectal plate glioma

Endoscopic Retrolabyrinthine Craniotomy for Exposure of the Trigeminal Nerve Root Entry Zone: Volumetric Analysis of Anatomic Exposure in the Cadaver.

Exposure of the root entry zone (REZ) of the trigeminal nerve (TN) for microvascular decompression is commonly obtained with a retrosigmoid approach, with or without endoscopic assistance. We hypothesized that adequate exposure of the TN REZ could be obtained through an endoscopic retrolabyrinthine (RL) approach. We aim to quantify exposure of the REZ of the TN using endoscopic RL approach, with and without drilling of the suprameatal tubercle of the internal auditory canal. Surgical dissection was performed bilaterally on 3 embalmed cadaveric human heads at the anatomy laboratory of the House Institute. Heads were scanned for volumetric analysis using 3D Slicer software both before and after dissection. Extent of exposure was quantified in 2 ways: first, by assessment of the surgeon's ability to visualize 16 predetermined anatomic landmarks with the endoscope and second, we estimated the "working" area by placing fiducials under the fully endoscopic view and calculating the resultant 3D volume. Using the standard endoscopic RL approach, an average of 13.8 landmarks (range 12-16) was visualized. The estimated working volume exposed by the RL on each side of each head varied from 189.28 to 527.85 mm3. Drilling of the suprameatal tubercle provided both increases in landmark visualization and, on average, an additional 55 mm3 of working volume. The endoscopic RL approach is a viable alternative to the standard retrosigmoid approach. Potential advantages of the RL include a more lateral trajectory that minimizes the need for cerebellar retraction and a shorter working distance and shallower angle to the cerebellopontine angle. Potential disadvantages include longer surgery time, increased technical difficulty of exposure, and potential for cerebrospinal fluid leak and or hearing loss.

Progress in study on animal models of trigeminal neuralgia.

Trigeminal neuralgia is a manifestation of orofacial neuropathic pain disorder, always deemed to be an insurmountable peak in the field of pain research and treatment. The pain is recurrent, abrupt in onset and termination similar to an electric shock or described as shooting. A poor quality of life has been attributed to trigeminal neuralgia, as the paroxysms of pain may be triggered by innocuous stimuli on the face or inside the oral cavity, such as talking, washing face, chewing and brushing teeth in daily life. The pathogenesis of trigeminal neuralgia has not been fully elucidated, although the microvascular compression in the trigeminal root entry zone is generally considered to be involved in the emergence and progression of the pain disorder. In addition, orofacial neuropathic pain restricted to one or more divisions of the trigeminal nerve might be secondary to peripheral nerve injury. Based on current hypotheses regarding the potential causes, a variety of animal models have been designed to simulate the pathogenesis of trigeminal neuralgia, including models of compression applied to the trigeminal nerve root or trigeminal ganglion, chronic peripheral nerve injury, peripheral inflammatory pain and center-induced pain. However, it has not yet been possible to determine which model can be perfectly employed to explain the mechanisms. The selection of appropriate animal models is of great significance for the study of trigeminal neuralgia. Therefore, it is necessary to discuss the characteristics of the animal models in terms of animal strains, materials, operation methods and behavior observation, in order to gain insight into the research progress in animal models of trigeminal neuralgia. In the future, animal models that closely resemble the features of human trigeminal neuralgia pathogenesis need to be developed, with the aim of making valuable contributions to the relevant basic and translational medical research.

Microvascular Decompression for Trigeminal Neuralgia Caused by Trigeminocerebellar Artery

The trigeminocerebellar artery(TCA)is a unique branch of the basilar artery. The TCA was first described in detail by Markovic et al. in 1996. The incidence of TCA was 6.9%-13.3% in previous cadaveric studies. The TCA branches from the distal part of the basilar artery, courses very close to the trigeminal nerve root entry zone, and occasionally twists or encircles the nerve root. A close relationship between the TCA and trigeminal nerve can cause trigeminal neuralgia(TN). This characteristic course of TCA requires adjuvant decompression techniques performed by the operators. In the microvascular decompression for TN caused by the TCA, operators should pay attention to the following: 1)sufficient arachnoid dissection around the TCA, 2)combined transposition and interposition technique, 3)decompression of perforators and vessels penetrating the nerve, and 4)recognition of the existence of the TCA.

A Rare Occurrence of Demyelinating Lesions of Bilateral Trigeminal Nerves: An Atypical Presentation of Pediatric Multiple Sclerosis

AbstractPontine trigeminal root entry zone is a typical, although uncommon, location for multiple sclerosis (MS) lesions to occur. Here, we present a 17-year-old girl with nausea, vomiting, and vertigo. Neurological examination was consistent with central nystagmus, positive Romberg's test, and left-sided hyperreflexia. Baseline magnetic resonance imaging fulfilled McDonald 2017 criteria for MS and showed T2-hyperintense and T1-hypointense bilateral demyelinating lesions at the intramedullary portion of the trigeminal root of the fifth nerve, with no contrast enhancement or restricted diffusion. Bilateral intrapontine trigeminal involvement is a rare finding in MS, as well as the combined central and peripheral demyelination. Furthermore, very limited information and cases have been described in pediatric patients.

Meckel’s cave compression with Teflon for the treatment of idiopathic trigeminal neuralgia: its possibility as a modified surgical technique

Objective: We analyzed the clinical outcomes of Meckel’s cave compression with Teflon (Rhee’s method) as a new modified and additional surgical technique for trigeminal neuralgia (TN).Methods: Between March 1996 and December 2014, out of 78 patients who were treated with microvascular decompression (MVD) or partial sensory root rhizotomy, 28 patients additionally underwent Meckel’s cave compression with Teflon. The mean age at initial treatment was 54.3 years (range: 40–69 years). The mean duration from onset to operation was 70.5 months (range: 5–360 months) and the mean follow-up period was 26 months (range: 1–77 months). Results: Fifteen patients (53.6%) had facial pain in the V2/V3 distribution. The offending or associating vessel was the superior cerebellar artery in four patients (14.3%), the superior petrosal vein in six (21.4%), the anterior inferior cerebellar artery in two (7.1%), multiple vessels in nine (32.1%), and miscellaneous arteries or veins in six (21.4%). One patient (3.6%) had no offending vessel, and seven patients were had no definite offending vessels that contacted the trigeminal root entry zone. Meckel’s cave compression with Teflon was applied to all patients: 10 (35.7%) in combination with MVD, one (3.6%) with partial rhizotomy, and 17 (60.7%) with both MVD and partial rhizotomy. TN was relieved in 26 patients (92.9%) and symptoms recurred in three patients (pain-free rate: 82.1%). The complication rate of this method appeared to be similar to other treatment procedures. Conclusion: Meckel’s cave compression with Teflon may be a safe and useful additional treatment procedure for TN.

Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor regulate the interaction between astrocytes and Schwann cells at the trigeminal root entry zone.

The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes. Its special anatomical and physiological structure renders it susceptible to nerve injury. The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone. This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions. Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. In monoculture, glial cell line-derived neurotrophic factor promoted the migration of Schwann cells, but it did not have effects on the migration of astrocytes. In the co-culture system, glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells. Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes. However, in the co-culture system, brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree. These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone. This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions.

Primary Glioblastoma of Trigeminal Root Entry Zone and Internal Auditory Canal: Case Report

Glioblastoma developed from cranial nerves are extremely rare. We report the case of a 71-year-old woman with glioblastoma arising from both trigeminal root entry zones and Internal Auditory Canal (IAC) nerves.

Blood-nerve barrier disruption and coagulation system activation induced by mechanical compression injury participate in the peripheral sensitization of trigeminal neuralgia.

The aim of this study was to investigate the effect and possible mechanisms of the blood-nerve barrier (BNB) and the coagulation-anticoagulation system in modulating the mechanical allodynia in a trigeminal neuralgia (TN) rat model induced by chronic compression of the trigeminal root entry zone (TREZ). Von Frey filaments were applied to determine the orofacial mechanical allodynia threshold. The BNB permeability was evaluated by Evans blue extravasation test. Immunohistochemical staining and laser confocal microscopy were used to measure the length of the depletion zones of the nodes of Ranvier in the TREZ, the diameter of nerve fibers and the length of the nodal gap. The transcriptional levels of prothrombin and endogenous thrombin inhibitor protease nexin-1 (PN-1) in the TREZ of TN rats were assessed by RT-qPCR. A Western blotting assay was performed to detect the expression of paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) in the TREZ. The spatiotemporal expression pattern of thrombin activated receptor (i.e. protease activated receptor 1, PAR1) in TREZ were defined by immunostaining and immunoblotting assays. PAR1 receptor inhibitors SCH79797 were administrated to TN rats to analyze the effect of thrombin-PAR1 on orofacial hyperalgesia. A compression injury of a rat's TREZ successfully induced TN-like behavior and was accompanied by the destruction of the permeability of the BNB and the promotion of prothrombin and thrombin inhibitor protease nexin-1 (PN-1) expression. The expression of the paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) was increased, while the nodal gap length of the nodes of Ranvier was widened and the length of node-depleted zones was shortened. Moreover, the expression of PAR1 within the TREZ was upregulated at an early stage of TN, and administration of the PAR1 antagonist SCH79797 effectively ameliorated orofacial mechanical allodynia. A compression injury of the TREZ increased the permeability of the BNB and induced disturbances in the local coagulation-anticoagulation system, concomitant with the structural changes in the nodes of Ranvier, thrombin-PAR1 may play a critical role in modulating orofacial mechanical hyperalgesia in a TN rat model.

Dosimetric Comparison between a Frameless Robotic Radiosurgery System and HyperArc Treatment Plans for Trigeminal Neuralgia: Cone-Based Robotic System vs. High-Definition MLC Based Linac System

<h3>Purpose/Objective(s)</h3> SRS is an effective and safe treatment option for trigeminal neuralgia (TN). Good dosimetric distribution has made HyperArc (HA) an attractive SRS/FRST technique for treating benign brain lesions. This study aims to evaluate the feasibility of HA for TN by comparing it with the dose distribution of frameless robotic radiosurgery systems. <h3>Materials/Methods</h3> Twenty patients with TN treated by cone-based CK were enrolled. The treatment location was targeted on the whole trigeminal nerve root entry zone (REZ) segment, leaving a 2-mm sparing from the brainstem. The prescription dose was 65 Gy in a single fraction, prescribing to the 80% isodose line with the highest dose of 81.25 Gy in the REZ. The segment of the trigeminal nerve encompassed by the 80% isodose line averaged 7.2 mm in length. Dose to brainstem surface was constrained with a maximum dose of 40 Gy. The corresponding HA plans were generated for the 20 patients to meet the same CK treatment plan criteria, using the high-definition MLC (2.5mm at the center) and SRS NTO optimization algorithm. The CK and HA treatment plans were compared with target coverage, sparing of organs at risk (OARs), and dose distribution metrics. <h3>Results</h3> All the OAR constraints were met in the HA treatment plans. The HA plans exhibited higher coverage of the PTVs than the CK plans, with statistically significant differences (HA vs. CK, 97.2% vs. 92.2%, P = 0.008). The HA plans consistently demonstrate better sparing of the OARs than the CK plans. The mean brain doses were 0.83 Gy and 1.15 Gy for HA and CK (P < 0.001), respectively. The brain V12 was significantly smaller with HA plans than with CK plans (5.9 c.c. in HA vs. 6.9 c.c. in CK, P = 0.019). Significant differences in the maximal and mean doses of the ipsilateral/contralateral CN VII/VIII were observed between the HA and CK plans. The HA plans exhibited a significantly greater conformity index than the CK plans (HA vs. CK, 1.59 vs. 1.71, P = 0.001). The dose gradient radius was similar in the CK and HA plans (HA, 0.28 vs. CK, 0.29). <h3>Conclusion</h3> Excellent sparing of OARs and good dosimetric distribution demonstrated HA is a feasible SRS technique for the treatment of TN. Further clinical studies using HA for TN would be necessary to confirm the therapeutic benefits and toxicity profiles.

A Preliminary Study of the Efficacy of Transcranial Direct Current Stimulation in Trigeminal Neuralgia.

The purpose of this study is to assess the efficacy of transcranial direct current stimulation (tDCS) in patients with treatment-refractory trigeminal neuralgia (TN) and examine the utility of neuroimaging methods in identifying markers of such efficacy. Six patients with classical TN refractory to maximal medical treatment, underwent tDCS (three cases inhibitory/cathodic and three cases excitatory/anodic stimulation). All patients underwent pre- and posttreatment functional magnetic resonance imaging (fMRI) during block-design tasks (i.e., Pain, Pain + tDCS, tDCS) as well as single-shell diffusion MRI (dMRI) acquisition. The precise locations of tDCS electrodes were identified by neuronavigation. Five therapeutic tDCS sessions were carried out for each patient with either anodic or cathodic applications. The Numeric Rating Scale of pain (NRS) and the Headache Disability Index (HDI) were used to score the subjective efficacy of treatment. Altered activity of regional sites was identified by fMRI and associated changes in the spinothalamocortical sensory tract (STCT) were measured by the dMRI indices of fractional anisotropy (FA) and mean diffusivity (MD). Fiber counts of the bilateral trigeminal root entry zone (REZ) were performed as an added measure of fiber loss or recovery. All patients experienced a significant reduction in pain scores with a substantial decline in HDI (P value < 0.01). Following a course of anodic tDCS, the ipsilateral caudate, globus pallidus, somatosensory cortex, and the contralateral globus pallidus showed a significantly attenuated activation whereas cathodic tDCS treatment resulted in attenuation of the thalamus and globus pallidus bilaterally, and the somatosensory cortex and anterior cingulate gyrus contralaterally. dMRI analysis identified a substantial increase (>50%) in the number of contralateral sensory fibers in the STCT with either anodic or cathodic tDCS treatment in four of the six patients. A significant reduction in FA (>40%) was observed in the ipsilateral REZ in the posttreatment phase in five of the six patients. Preliminary evidence suggests that navigated tDCS presents a promising method for alleviating the pain of TN. Different patterns of activation manifested by anodic and cathodic stimulation require further elaboration to understand their implication. Activation and attenuation of responses at various sites may provide further avenues for condition treatment.

Treatment of redo-microvascular decompression or internal neurolysis plus microvascular decompression for recurrent trigeminal neuralgia: a review of long-term effectiveness and safety.

ObjectiveWe examined the clinical characteristics and outcomes of patients with recurrent trigeminal neuralgia (TN) and assessed the long-term efficacy and safety of microvascular decompression (MVD) to treat typical recurrent TN.MethodsWe identified 3024 patients who underwent MVD for treatment of TN at the China-Japan Friendship Hospital from March 2009 to December 2020. We retrospectively analyzed the data and outcomes of 137 patients who underwent redo-MVD and 74 patients who did not undergo redo-MVD as the control group. These outcomes were evaluated using the Barrow Neurological Institute scoring system.ResultsRecurrence in 68 of the 137 patients was due to incomplete or absent decompression or new responsible vessels. To ensure thorough pain relief, redo-MVD should include decompression of both the trigeminal root entry zone and the peripheral nerve segments, where blood vessels can cause symptoms. Factors associated with reduced effectiveness of redo-MVD were no period of initial pain relief after the first MVD and a longer duration of symptoms before the first MVD.ConclusionsRedo-MVD should not be excluded as a treatment option for patients with refractory TN who develop recurrent pain after a first MVD procedure.

White matter volume loss drives cortical reshaping after thalamic infarcts

ObjectiveThe integration of somatosensory, ocular motor and vestibular signals is necessary for self-location in space and goal-directed action. We aimed to detect remote changes in the cerebral cortex after thalamic infarcts to reveal the thalamo-cortical connections necessary for multisensory processing and ocular motor control. MethodsThirteen patients with unilateral ischemic thalamic infarcts presenting with vestibular, somatosensory, and ocular motor symptoms were examined longitudinally in the acute phase and after six months. Voxel- and surface-based morphometry were used to detect changes in vestibular and multisensory cortical areas and known hubs of central ocular motor processing. The results were compared with functional connectivity data in 50 healthy volunteers. ResultsPatients with paramedian infarcts showed impaired saccades and vestibular perception, i.e., tilts of the subjective visual vertical (SVV). The most common complaint in these patients was double vision or vertigo / dizziness. Posterolateral thalamic infarcts led to tilts of the SVV and somatosensory deficits without vertigo. Tilts of the SVV were higher in paramedian compared to posterolateral infarcts (median 11.2° vs 3.8°). Vestibular and ocular motor symptoms recovered within six months. Somatosensory deficits persisted. Structural longitudinal imaging showed significant volume reduction in subcortical structures connected to the infarcted thalamic nuclei (vestibular nuclei region, dentate nucleus region, trigeminal root entry zone, medial lemniscus, superior colliculi). Volume loss was evident in connections to the frontal, parietal and cingulate lobes. Changes were larger in the ipsilesional hemisphere but were also detected in homotopical regions contralesionally. The white matter volume reduction led to deformation of the cortical projection zones of the infarcted nuclei. ConclusionsWhite matter volume loss after thalamic infarcts reflects sensory input from the brainstem as well the cortical projections of the main affected nuclei for sensory and ocular motor processing. Changes in the cortical geometry seem not to reflect gray matter atrophy but rather reshaping of the cortical surface due to the underlying white matter atrophy.

Automated Segmentation of Trigeminal Nerve and Cerebrovasculature in MR-Angiography Images by Deep Learning.

Trigeminal neuralgia caused by paroxysmal and severe pain in the distribution of the trigeminal nerve is a rare chronic pain disorder. It is generally accepted that compression of the trigeminal root entry zone by vascular structures is the major cause of primary trigeminal neuralgia, and vascular decompression is the prior choice in neurosurgical treatment. Therefore, accurate preoperative modeling/segmentation/visualization of trigeminal nerve and its surrounding cerebrovascular is important to surgical planning. In this paper, we propose an automated method to segment trigeminal nerve and its surrounding cerebrovascular in the root entry zone, and to further reconstruct and visual these anatomical structures in three-dimensional (3D) Magnetic Resonance Angiography (MRA). The proposed method contains a two-stage neural network. Firstly, a preliminary confidence map of different anatomical structures is produced by a coarse segmentation stage. Secondly, a refinement segmentation stage is proposed to refine and optimize the coarse segmentation map. To model the spatial and morphological relationship between trigeminal nerve and cerebrovascular structures, the proposed network detects the trigeminal nerve, cerebrovasculature, and brainstem simultaneously. The method has been evaluated on a dataset including 50 MRA volumes, and the experimental results show the state-of-the-art performance of the proposed method with an average Dice similarity coefficient, Hausdorff distance, and average surface distance error of 0.8645, 0.2414, and 0.4296 on multi-tissue segmentation, respectively.

Flow cytometry analysis of immune and glial cells in a trigeminal neuralgia rat model

Microvascular compression of the trigeminal root entry zone (TREZ) is the main cause of most primary trigeminal neuralgia (TN), change of glial plasticity was previously studied in the TREZ of TN rat model induced by chronic compression. To better understand the role of astrocytes and immune cells in the TREZ, different cell markers including glial fibrillary acidic protein (GFAP), complement C3, S100A10, CD45, CD11b, glutamate-aspartate transporter (GLAST), Iba-1 and TMEM119 were used in the TN rat model by immunohistochemistry and flow cytometry. On the post operation day 28, GFAP/C3-positive A1 astrocytes and GFAP/S100A10-positive A2 astrocytes were activated in the TREZ after compression injury, there were no statistical differences in the ratios of A1/A2 astrocytes between the sham and TN groups. There was no significant difference in Iba-1-positive cells between the two groups. The ratios of infiltrating lymphocytes (CD45+CD11b−) (p = 0.0075) and infiltrating macrophages (CD45highCD11b+) (p = 0.0388) were significantly higher than those of the sham group. In conclusion, different subtypes A1/A2 astrocytes in the TREZ were activated after compression injury, infiltrating macrophages and lymphocytes increased, these neuroimmune cells in the TREZ may participate in the pathogenesis of TN rat model.

Technical note: A spiral fluid-attenuated inversion recovery magnetic resonance imaging technique for stereotactic radiosurgery treatment planning for trigeminal neuralgia.

Magnetic resonance imaging (MRI) is commonly used in treatment planning for stereotactic radiosurgery (SRS) of trigeminal neuralgia (TN). With current MRI techniques, the delineation of the trigeminal nerve root entry zone (REZ) may be degraded due to poor contrast and artifacts. The purpose of this work is to develop an MRI technique with better delineation of the trigeminal nerve REZ to improve SRS treatment planning for TN. A spiral fluid-attenuated inversion recovery (FLAIR) MRI technique was developed to improve image quality by improving tissue contrast, fluid suppression, artifact reduction, and signal-to-noise ratio (SNR). A concomitant-phase compensation method based on spiral gradient waveforms was implemented to minimize artifacts due to magnetic field change induced by the metal frame used in Gamma Knife treatment planning. The image quality of spiral FLAIR was assessed in four healthy volunteers. The geometric accuracy was quantitatively evaluated by registering spiral FLAIR to computed tomography (CT) images and comparing it with existing MRI techniques. The spiral FLAIR technique demonstrated better delineation of the trigeminal nerve REZ, improved tissue contrast of the brain stem, and minimized flow artifacts, compared to steady-state free precession (SSFP) MRI. Spiral FLAIR also improved fluid suppression, SNR, and artifacts, which contributed to better delineation of the trigeminal nerve REZ compared to conventional Cartesian FLAIR. The measured mean (± standard deviation) distance between spiral FLAIR and CT images is 0.98 ± 0.56mm, comparable to 0.40 ± 0.26mm in 3T T1 spoiled gradient echo (T1-SPGR), 0.59 ± 0.25mm in 3T SSFP, 0.66 ± 0.38mm in 1.5T T1-SPGR, and 0.61 ± 0.25mm in 1.5T Cartesian FLAIR. A spiral FLAIR technique with improved image quality and good geometric accuracy provides a potential alternative for treatment planning in SRS for TN patients.

Right medium-sized vestibular schwannoma with trigeminal neuralgia post-fractionated radiotherapy.

A patient with trigeminal neuralgia secondary to a vestibular schwannoma underwent fractionated radiotherapy without relief of her pain. She was then effectively treated with microsurgical resection of her tumor. Early identification of the lower cranial nerves and the origin of the facial and vestibulocochlear nerves is key to determining the operative corridors for vestibular schwannoma resection. To effectively treat trigeminal neuralgia, the trigeminal nerve root entry zone and motor branch are clearly identified and decompressed. Fractioned radiotherapy does not effectively treat trigeminal neuralgia secondary to vestibular schwannoma compression.The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID21112

Using RNA-Seq to Explore the Hub Genes in the Trigeminal Root Entry Zone of Rats by Compression Injury

Mechanical compression on the trigeminal root entry zone (TREZ) by microvascular is the main etiology of primary trigeminal neuralgia (TN). To study the pathogenesis of TN, hub genes screening in the TREZ of TN in an animal model was performed. A double blind, randomized study was designed in a controlled animal trial. The research took place in the Laboratory of Clinical Applied Anatomy at the School of Basic Medical Science of Fujian Medical University. Twelve male rats were randomly divided into a sham operation group and a TN animal model group. TN animal model was induced by chronic compression of trigeminal nerve root (CCT) operation. Gene expression in the TREZ were analyzed by RNA sequencing (RNA-Seq) technique. KEGG analysis, GO analysis, and PPI analysis were performed in the DEGs. Key signaling pathways analyzing by GSEA and the hub genes in the DEGs were also studied. Reverse transcription real-time polymerase chain reaction (RT-qPCR) was used to verify the RNA-Seq results. Transcriptome data showed that 352 genes up-regulated and 59 genes down-regulated in DEGs on post-operation day 21, after CCT operation in the TN group. KEGG analysis revealed that, "neuroactive ligand receptor interaction" and "cytokine cytokine receptor interaction" may be related to the pathogenesis of TN. GO analysis showed "regulation of signing receptor activity", "chemokine activity", and "carbohydrate binging" may be related to TN. The RT-qPCR results were consistent with the test results, indicating that the transcriptome sequencing results were reliable. Although the incidence of TN in female rats was higher than in male rats, we only used male SD rats to establish the TN animal model, to avoid the effect of estrogen on experimental results. This study only presents some respects of RNA-Seq technique and, therefore, did not identify the DEGs at the protein level. The relationship between the DEGs at different levels shoud be done in the future. Based on the results of RNA-seq, this study discovered 6 hub genes in the TREZ that are closely related to the TN animal model, which provide a potential breakthrough point to explore the pathogenesis of TN.

Potential Molecular Targets for Treating Neuropathic Orofacial Pain Based on Current Findings in Animal Models.

This review highlights potential molecular targets for treating neuropathic orofacial pain based on current findings in animal models. Preclinical research is currently elucidating the pathophysiology of the disease and identifying the molecular targets for better therapies using animal models that mimic this category of orofacial pain, especially post-traumatic trigeminal neuropathic pain (PTNP) and primary trigeminal neuralgia (PTN). Animal models of PTNP and PTN simulate their etiologies, that is, trauma to the trigeminal nerve branch and compression of the trigeminal root entry zone, respectively. Investigations in these animal models have suggested that biological processes, including inflammation, enhanced neuropeptide-mediated pain signal transmission, axonal ectopic discharges, and enhancement of interactions between neurons and glial cells in the trigeminal pathway, are underlying orofacial pain phenotypes. The molecules associated with biological processes, whose expressions are substantially altered following trigeminal nerve damage or compression of the trigeminal nerve root, are potentially involved in the generation and/or exacerbation of neuropathic orofacial pain and can be potential molecular targets for the discovery of better therapies. Application of therapeutic candidates, which act on the molecular targets and modulate biological processes, attenuates pain-associated behaviors in animal models. Such therapeutic candidates including calcitonin gene-related peptide receptor antagonists that have a reasonable mechanism for ameliorating neuropathic orofacial pain and meet the requirements for safe administration to humans seem worth to be evaluated in clinical trials. Such prospective translation of the efficacy of therapeutic candidates from animal models to human patients would help develop better therapies for neuropathic orofacial pain.