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Craniofacial pain is prevalent and a debilitating condition. Managing craniofacial pain is particularly challenging due to its multifaceted nature. Among the most severe forms of craniofacial pain is trigeminal neuralgia, often described as one of the most excruciating pain syndromes encountered in clinical practice. Utilizing a mouse model of trigeminal neuropathic pain, we found severe mitochondrial impairment in the injured trigeminal ganglion (TG), spanning transcription and translation to functionality. Our findings demonstrated that rejuvenating mitochondria by boosting NAD +  levels enhanced mitochondrial fitness and significantly ameliorated trigeminal neuropathic pain. Additionally, we showed that the analgesic effects of nicotinamide riboside (NR) supplementation mainly depend on Sirt1. Importantly, our multi-omics studies revealed that activated Sirt1 by NR suppresses a broad range of key pain genes and exerts anti-inflammatory effects in the TG. Together, we present a comprehensive view of how mitochondrial dysfunction is involved in trigeminal neuropathic pain. Therefore, targeting mitochondrial dysfunction offers a novel and promising approach to craniofacial pain management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Structural covariance networks and causal effects within can provide critical information on gray matter reorganization and disease-related hierarchical changes. Based on the T1WI data of 43 classical trigeminal neuralgia patients and 45 controls, we constructed morphological similarity networks of cortical thickness, sulcal depth, fractal dimension, and gyrification index. Moreover, causal structural covariance network analyses were conducted in regions with morphological abnormalities or altered nodal properties, respectively. We found that patients showed reduced sulcal depth, gyrification index, and fractal dimension, especially in the salience network and the default mode network. Additionally, the integration of the fractal dimension and sulcal depth networks was significantly reduced, accompanied by decreased nodal efficiency of the bilateral temporal poles, and right pericalcarine cortex within the sulcal depth network. Negative causal effects existed from the left insula to the right caudal anterior cingulate cortex in the gyrification index map, also from bilateral temporal poles to right pericalcarine cortex within the sulcal depth network. Collectively, patients exhibited impaired integrity of the covariance networks in addition to the abnormal gray matter morphology in the salience network and default mode network. Furthermore, the patients may experience progressive impairment in the salience network and from the limbic system to the sensory system in network topology, respectively., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Idiopathic trigeminal neuralgia (TN) cases encountered frequently in daily practice indicate significant gaps that still need to be illuminated in the etiopathogenesis. In this study, a novel TN animal model was developed by compressing the dorsal horn (DH) of the upper cervical spinal cord., Methods: Eighteen rabbits were equally divided into three groups, namely control (CG), sham (SG), and spinal cord compression (SCC) groups. External pressure was applied to the left side at the C3 level in the SCC group. Dorsal hemilaminectomy was performed in the SG, and the operative side was closed without compression. No procedure was implemented in the control group. Samples from the SC, TG, and ION were taken after seven days. For the histochemical staining, damage and axons with myelin were scored using Hematoxylin and Eosin and Toluidine Blue, respectively. Immunohistochemistry, nuclei, apoptotic index, astrocyte activity, microglial labeling, and CD11b were evaluated., Results: Mechanical allodynia was observed on the ipsilateral side in the SCC group. In addition, both the TG and ION were partially damaged from SC compression, which resulted in significant histopathological changes and increased the expression of all markers in both the SG and SCC groups compared to that in the CG. There was a notable increase in tissue damage, an increase in the number of apoptotic nuclei, an increase in the apoptotic index, an indication of astrocytic gliosis, and an upsurge in microglial cells. Significant increases were noted in the SG group, whereas more pronounced significant increases were observed in the SCC group. Transmission electron microscopy revealed myelin damage, mitochondrial disruption, and increased anchoring particles. Similar changes were observed to a lesser extent in the contralateral spinal cord., Conclusion: Ipsilateral trigeminal neuropathic pain was developed due to upper cervical SCC. The clinical finding is supported by immunohistochemical and ultrastructural changes. Thus, alterations in the DH due to compression of the upper cervical region should be considered as a potential cause of idiopathic TN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The cellular distribution and changes in CX3CL1/fractalkine and its receptor CX3CR1 protein levels in the trigeminal subnucleus caudalis (TSC) of rats with unilateral infraorbital nerve ligation (IONL) were investigated on postoperation days 1, 3, 7, and 14 (POD1, POD3, POD7, and POD14, respectively) and compared with those of sham-operated and naïve controls. Behavioral tests revealed a significant increase in tactile hypersensitivity bilaterally in the vibrissal pads of both sham- and IONL-operated animals from POD1 to POD7, with a trend towards normalization in sham controls at POD14. Image analysis revealed increased CX3CL1 immunofluorescence (IF) intensities bilaterally in the TSC neurons of both sham- and IONL-operated rats at all survival periods. Reactive astrocytes in the ipsilateral TSC also displayed CX3CL1-IF from POD3 to POD14. At POD1 and POD3, microglial cells showed high levels of CX3CR1-IF, which decreased by POD7 and POD14. Conversely, CX3CR1 was increased in TSC neurons and reactive astrocytes at POD7 and POD14, which coincided with high levels of CX3CL1-IF and ADAM17-IF. This indicates that CX3CL1/CX3CR1 may be involved in reciprocal signaling between TSC neurons and reactive astrocytes. The level of CatS-IF in microglial cells suggests that soluble CX3CL1 may be involved in neuron-microglial cell signaling at POD3 and POD7, while ADAM17 allows this release at all studied time points. These results indicate an extended CX3CL1/CX3CR1 signaling axis and its role in the crosstalk between TSC neurons and glial cells during the development of trigeminal neuropathic pain.

Background: Trigeminal neuralgia (TN) is the most severe type of neuropathic pain. The trigeminal ganglion (TG) is a crucial target for the pathogenesis and treatment of TN. The colony-stimulating factor 1 (CSF1) - colony-stimulating factor 1 receptor (CSF1R) pathway regulates lower limb pain development. However, the effect and mechanism of the CSF1-CSF1R pathway in TG on TN are unclear., Methods: Partial transection of the infraorbital nerve (pT-ION) model was used to generate a mouse TN model. Mechanical and cold allodynia were used to measure pain behaviors. Pro-inflammatory factors (IL-6, TNF-a) were used to measure inflammatory responses in TG. PLX3397, an inhibitor of CSF1R, was applied to inhibit the CSF1-CSF1R pathway in TG. This pathway was activated in naïve mice by stereotactic injection of CSF1 into the TG., Results: The TN model activated the CSF1-CSF1R pathway in the TG, leading to exacerbated mechanical and cold allodynia. TN activated inflammatory responses in the TG manifested as a significant increase in IL-6 and TNF-a levels. After using PLX3397 to inhibit CSF1R, CSF1R expression in the TG declined significantly. Inhibiting the CSF1-CSF1R pathway in the TG downregulated the expression of IL-6 and TNF-α to reduce allodynia-related behaviors. Finally, mechanical allodynia behaviors were exacerbated in naïve mice after activating the CSF1-CSF1R pathway in the TG., Conclusions: The CSF1-CSF1R pathway in the TG modulates TN by regulating neuroimmune responses. Our findings provide a theoretical basis for the development of treatments for TN in the TG., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Various neuropathies of the cranil nerves can accompany trigeminal neuropathic pain attributed to space-occupying lesions. In this case report, the patient presented with persistent intraoral pain and numbness on the right side of the face. Cranial nerve examination revealed dysfunctional eye movements, diplopia, and mechanical hyposensitivity in the mandibular region. The patient was diagnosed with neuropathy due to intracranial lesions and referred to the Department of Neurosurgery and Otorhinolaryngology. The patient was suspected of having malignant lymphoma and is currently undergoing neurosurgical intervention. This article discusses the importance of the examination of the cranial nerve for patients with persistent pain in the trigeminal nerve distribution.

Objective: High-resolution magnetic resonance imaging (MRI) of the trigeminal nerve is indispensable for workup of trigeminal neuralgia (TN) before microvascular decompression; however, the evaluation is often subjective and prone to variability. We aim to develop and assess sequential thresholding-based automated reconstruction of the trigeminal nerve (STAR-TN) as an algorithm for segmenting the trigeminal nerve and contacting structures that will allow for a structured method for assessing neurovascular conflict., Methods: A total of 42 patients with TN who underwent high-resolution MRI before microvascular decompression in 2022 were included in our study. Segmentation of the trigeminal nerve and contacting structures was performed on preoperative MRI scans using STAR-TN. The segmentations were then evaluated for neurovascular conflict and compared to the preoperative radiology and operative notes. Geometric features, including the area of contact and distance to conflict, were extracted., Results: Of the 42 patients, 32 (76.2%) were found to show neurovascular conflict based solely on their STAR-TN segmentations and 10 (23.8%) were found to not show neurovascular conflict. Compared with the intraoperative findings, this resulted in a sensitivity of 78.0% and specificity of 100%. In contrast, assessments of neurovascular conflict by radiologists using only 2-dimensional MRI views had a sensitivity of 68.3% and specificity of 100%. Of the 32 patients with neurovascular conflict, 29 (90.9%) had conflict within the root entry zone. Overall, the patients had a median area of contact of 10.66 mm 2 ., Conclusions: STAR-TN allows for 3-dimensional visualization and identification of neurovascular conflict with improved sensitivity compared with neuroradiologist assessments from MRI slices., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This review aims to systematically summarize the methods of establishing various models of trigeminal neuralgia (TN), the scope of application, and current animals used in TN research and the corresponding pain measurements, hoping to provide valuable reference for researchers to select appropriate TN animal models and make contributions to the research of pathophysiology and management of the disease., Design: The related literatures of TN were searched through PubMed database using different combinations of the following terms and keywords including but not limited: animal models, trigeminal neuralgia, orofacial neuropathic pain. To find the maximum number of eligible articles, no filters were used in the search. The references of eligible studies were analyzed and reviewed comprehensively., Results: This study summarized the current animal models of TN, categorized them into the following groups: chemical induction, photochemical induction, surgery and genetic engineering, and introduced various measurement methods to evaluate animal pain behaviors., Conclusions: Although a variety of methods are used to establish disease models, there is no ideal TN model that can reflect all the characteristics of the disease. Therefore, there is still a need to develop more novel animal models in order to further study the etiology, pathological mechanism and potential treatment of TN., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The association between trigeminal neuralgia (TN) and multiple sclerosis (MS) is well established. Many MS patients with TN have magnetic resonance imaging (MRI) evidence of a symptomatic demyelinating lesion. Although infratentorial presentations are included in the diagnostic criteria for MS, there remains confusion in clinical practice as to whether TN should be considered a clinically isolated syndrome for the application of McDonald criteria. In this case series, we discuss this diagnostic quandary in patients presenting with TN and additional MRI findings suggestive of MS and highlight the unmet need for data in such patients to optimally guide their care.

Background and Purpose: Patients suffering from trigeminal neuralgia are often accompanied by anxiety and depression. Microglia-mediated neuroinflammation is involved in the development of neuropathic pain and anxiodepression pathogenesis. Whether and how microglia are involved in trigeminal neuralgia-induced anxiodepression remains unclear., Experimental Approach: Unilateral constriction of the infraorbital nerve (CION) was performed to establish trigeminal neuralgia in rat and mouse models. Mechanical allodynia and anxiodepressive-like behaviours were measured. Optogenetic and pharmacological manipulations were employed to investigate the role of hippocampal microglia in anxiety and depression caused by trigeminal neuralgia., Key Results: Trigeminal neuralgia activated ipsilateral but not contralateral hippocampal microglia, up-regulated ipsilateral hippocampal ATP and interleukin-1β (IL-1β) levels, impaired ipsilateral hippocampal long-term potentiation (LTP) and induced anxiodepressive-like behaviours in a time-dependent manner in rodents. Pharmacological or optogenetic inhibition of ipsilateral hippocampal microglia completely blocked trigeminal neuralgia-induced anxiodepressive-like behaviours. Activation of unilateral hippocampal microglia directly elicited an anxiodepressive state and impaired hippocampal LTP. Knockdown of ipsilateral hippocampal P2X7 receptors prevented trigeminal neuralgia-induced microglial activation and anxiodepressive-like behaviours. Furthermore, we demonstrated that microglia-derived IL-1β mediated microglial activation-induced anxiodepressive-like behaviours and LTP impairment., Conclusion and Implications: These findings suggest that priming of microglia with ATP/P2X7 receptors in the ipsilateral hippocampus drives pain-related anxiodepressive-like behaviours via IL-1β. An asymmetric role of the bilateral hippocampus in trigeminal neuralgia-induced anxiety and depression was uncovered. The approaches targeting microglia and P2X7 signalling might offer novel therapies for trigeminal neuralgia-related anxiety and depressive disorder., (© 2022 British Pharmacological Society.)

Introduction: The aim is to establish a rat model of infraorbital neuroinflammation with less trauma, stable pain, and a long duration of pain. The pathogenesis of TN is not fully clear. There are various models of TN in rats with different disadvantages, such as damaging the surrounding structures and inaccuracy of location for infraorbital nerve (ION). We aim to establish a rat model of infraorbital neuroinflammation with minimal trauma, a simple operation, and accurate positioning under CT guidance to help us study the pathogenesis of trigeminal neuralgia., Methods: Thirty-six adult male Sprague Dawley rats (180-220 g) were randomly divided into 2 groups and injected with talc suspension or saline through the infraorbital foramen (IOF) under CT guidance. Mechanical thresholds were measured in the right ION innervation region of 24 rats over 12 postoperative weeks. At 4 weeks, 8 weeks, and 12 weeks after the operation, the inflammatory involvement of the surgical area was evaluated by MRI, and neuropathy was observed using a transmission electron microscope (TEM)., Results: The talc group had a significant decrease in the mechanical threshold at 3 days after surgery that continued until 12 weeks post-operation, and the talc group had a significantly lower mechanical threshold than the saline group 10 weeks post-operation. The talc group had significantly impaired trigeminal nerve (TGN) myelin after 8 weeks post-operation., Conclusion: The rat model of infraorbital neuroinflammation established by CT-guided injection of talc into the IOF is a simple operation that results in less trauma, stable pain, and a long duration of pain. Moreover, infraorbital neuroinflammation in peripheral branches of the TGN can cause demyelination of the TGN in the intracranial segment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Preoperative magnetic resonance imaging (MRI) is a standard component of the preoperative clinical workup for patients before microvascular decompression (MVD). However, its ability to accurately exclude neurovascular compression of the trigeminal nerve is not well understood., Methods: We retrospectively reviewed 1020 patients with available preoperative MRI data before microvascular decompression. General patient demographics and clinical characteristics were collected for each case. We recorded both evidence of neurovascular conflict on preoperative MRI radiology notes and intraoperative compression from operative notes. Sensitivity, specificity, positive predictive value, and negative predictive value were determined for general MRI, high-resolution MRI, and non-high resolution., Results: Overall, preoperative MRI before MVD showed a sensitivity of 75.8%, specificity of 65.8%, positive predictive value of 92.4%, and negative predictive value of 33.3% in predicting neurovascular compression of the trigeminal nerve. In particular, MRI was unable to identify 21.0% cases of sole arterial compression, 42.5% cases of sole venous compression, and combined arterial and venous compression in 18.5% of cases. A total of 958 patients (93.9%) underwent high-resolution preoperative MRI with skull base sequences. This imaging showed a sensitivity of 75.6%, specificity of 66.9%, positive predictive value of 92.5% and a negative predictive value of 33.4% in predicting trigeminal nerve neurovascular compression. Non-high-resolution MRI showed a sensitivity of 78.8%, specificity of 50.0%, positive predictive value of 89.1%, and negative predictive value of 31.3%. The negative predictive values of general, high-resolution, and non-high-resolution MRIs were all <50%., Conclusions: Preoperative MRI may offer a high predictive value for neurovascular conflict and should be part of the standard preoperative care workup for patients with trigeminal neuralgia. However, lack of neurovascular conflict on preoperative imaging is not sufficient to exclude patients from undergoing MVD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Primary trigeminal neuralgia (PTN) is characterized by chronic neuropathic pain. There are few studies exploring masticatory muscle changes in patients with PTN. This study evaluated the changes in the masticatory muscles using magnetic resonance imaging (MRI) and the predictive factors of masticatory muscle changes in patients with PTN. The radiologic outcomes of 52 patients with PTN and 58 healthy adults were evaluated. The temporalis, lateral pterygoid, medial pterygoid, and masseter muscles were assessed using MRI. Atrophy and edema of the masticatory muscles were noted. Multivariate analyses were conducted to identify factors associated with masticatory muscle atrophy. Among the PTN group, the right side (61.5%) and mandibular branch (53.9%) were the most affected. Muscle atrophy of the temporalis (P < .001), medial pterygoid (P = .016), lateral pterygoid (P = .031), and masseter (P = .001) were significantly higher in the PTN group than in the control group. Lateral pterygoid edema was significantly higher in the PTN group (P < .001). However, no significant difference was found in the temporalis and masseter edema between the two groups. Logistic regression analysis demonstrated that neurovascular conflict (NVC) significantly predicted mastication muscle atrophy (P = .037). Patients with PTN had higher rates of masticatory muscle atrophy and edema. The assessment of NVC may be a preoperative imaging biomarker to predict atrophy in PTN., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Trigeminal neuralgia occurs in the orofacial region, characteristically causing pain that feels like a transient electric shock. Some histopathological studies have reported that trigeminal neuralgia is caused by mechanical compression of the demyelinated trigeminal nerve; the pathophysiological mechanism behind this phenomenon remains to be clarified, however. Cell-cell interactions have also been reported to be involved in the development and modulation of some types of neuropathic pain. The purpose of this study was to investigate the potential contribution of cell-cell interactions to trigeminal neuralgia by measuring intracellular free Ca 2+ concentrations ([Ca 2+ ] i ) in primary cultured trigeminal ganglion (TG) cells. Direct mechanical stimulation of TG cells induced an increase in [Ca 2+ ] i in both neuronal and non-neuronal cells, such as glial cells. Moreover, this increase was stimulus intensity-dependent and non-desensitizing. Direct mechanical stimulation increased [Ca 2+ ] i in neighboring cells as well, and this increase was inhibited by application of carbamazepine. These results indicate that direct mechanical stimulation affects Ca 2+ signaling. Trigeminal ganglion cells establish intercellular networks between themselves, suggesting that this is involved in the development and generation of trigeminal neuralgia.

Background: The Gasserian ganglion (GG) is the primary neuronal aggregation area of the trigeminal nervous system and the epidural structure outside the central nervous system, thus, it has become the most commonly used target for minimally invasive treatment of trigeminal neuralgia (TN). Whether it is the classic trigeminal radiofrequency treatment or GG balloon compression therapy, the intervention target is the GG. The anatomy and imaging anatomy of the GG of the trigeminal nerve is of great importance in the minimally invasive treatment of TN., Objective: To study the anatomy of the trigeminal nerve and multimodal image fusion, and to provide a basis for a clinical minimally invasive interventional treatment forTN., Study Design: Review, clinical research study., Setting: Department of Anesthesiology and Pain Medical Center, Jiaxing, China., Methods: Dissect the general structure of the trigeminal nerve and its positional relationship with adjacent structures, and use computed tomography (CT) and magnetic resonance imaging (MRI) to observe the trigeminal nerve, and then, perform a fusion of the CT/MR images., Results: The GG of the trigeminal nerve is located in Meckel's cave of the middle cranial fossa, and the 3 branches of the nerve fibers are intertwined. CT could only clearly show the bony structures adjacent to the GG, rather than the GG in the body, which was inconsistent with MR images. The bony structure was blurred, while the Meckel's cave and nerve roots, where the trigeminal nerve is located, could be clearly distinguished. Fusing the CT/MR images could provide 2 complementary advantages., Limitations: It does not prove the the balloon position thought to be a "dumbbell" shape is adequate for the successful treatment., Conclusion: Based on the anatomical structure and position of the trigeminal nerve, it is difficult to achieve highly selective branch treatment of TN with radiofrequency in the GG. For the treatment of TN with percutaneous microballoon compression on the GG, the balloon catheter should be placed in Meckel's cave. While it is not easy to insert into Meckel's cave, the depth of the balloon catheter should be that the distal end is flush with the top of the temporal bone petrous cone.

Background: Trigeminal neuralgia (TN) is the most common type of chronic neuropathic facial pain, but the etiology and pathophysiological mechanisms after treatment are still not well understood. The purpose of this study was to investigate the longitudinal changes of the cisternal segment of the trigeminal nerve and brain pain-related regions in patients with TN before and after treatment using readout segmentation of long variable echo-train (RESOLVE) diffusion tensor imaging (DTI) and transverse relaxation (T2)-weighted sampling perfection with application-optimized contrast at different flip angle evolutions (T2-SPACE)., Methods: Twelve patients with TN and four healthy controls were enrolled in this study. All patients underwent assessment of the visual analog scale (VAS), and acquisition of RESOLVE DTI and T2-SPACE images before and at 1, 6, and 12 months after treatments. Regions-of-interest were placed on the bilateral anterior, middle, and posterior parts of the cisternal segment of the trigeminal nerve, the bilateral root entry zone (REZ), bilateral nuclear zone, and the center of pontocerebellar tracts, respectively. Voxel-based morphometry (VBM) analysis was conducted with T2-SPACE images, and gray matter volumes (GMV) were measured from brain pain-matrix regions., Results: The results demonstrated that the VAS scores, the axial diffusivity of the middle part of the affected cisternal trigeminal nerve, the fractional anisotropy of the bilateral nuclear zones, and the mean diffusivity of the center of pontocerebellar tract significantly changed over time before and after treatment. The changes of GMV in the pain-matrix regions exhibited similar trends to the VAS before and after treatment., Conclusion: We conclude that magnetic resonance imaging with RESOLVE DTI and VBM with T2-SPACE images were helpful in the understanding of the pathophysiological mechanisms in patients with TN before and after treatment., (© 2021. The Author(s).)

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., (© 2021. The Author(s).)

Trigeminal neuralgia (TN) is a disease of unclear pathogenesis. It has a low incidence and is not fatal, but it can cause afflicted patients' depression or suicide. In the past, neurovascular compression was considered to be the main cause of TN, but recent studies have found that neurovascular contact is also common in asymptomatic patients and the asymptomatic side in symptomatic patients. This indicates that the neurovascular contact is not, or is only to a lesser extent, a factor in the development of TN. Thus, the study of the peripheral branches of the trigeminal nerve is necessary to understand the etiology of TN. With the development of imaging technology and the emergence of various imaging modalities, it is possible to study the etiology of TN and the pathological changes of related structures by magnetic resonance neuroimaging. This article reviews the recent advances in magnetic resonance neuroimaging of the trigeminal nerve.

Our previous study showed that silencing of lncRNA Gm14461 alleviated pain in a murine model of trigeminal neuralgia (TN), but the molecular mechanism remains not fully understood. Evidence indicates that astrocyte activation and autophagy are involved in the development of TN. Herein, this study aimed to elucidate whether the pain-relief effect of Gm14461 silencing in TN involved regulation of astrocyte activation and autophagy. A murine model of TN was induced by chronic constriction injury of the infraorbital nerve surgery. The mechanical withdrawal threshold (MWT) was measured to assess the analgesic effect of Gm14461 silencing. Mouse astrocytes were treated with lipopolysaccharide (LPS) as a cell model. Astrocyte activation was evaluated by glial fibrillary acidic protein (GFAP) immunofluorescence and western blot analysis of GFAP. Autophagy was evaluated by LC3 immunofluorescence and western blot analysis of autophagy-related proteins. The results showed that Gm14461 silencing increased MWT value in TN model mice. Meanwhile, Gm14461 silencing inhibited astrocyte activation and enhanced autophagy in both TN mice and LPS-treated astrocytes. The enhancement of autophagy by Gm14461 silencing involved the activation of the AMPK signaling and the suppression of the Akt/mTOR signaling. Collectively, the analgesic effect of Gm14461 silencing in TN was related to attenuation of astrocyte activation via enhancement of autophagy., (© 2020 International Union of Biochemistry and Molecular Biology.)

The superior cerebellar artery (SCA) is the most frequent offending vessel in trigeminal neuralgia. This study aims to elucidate the patterns of the SCA running in 34 patients with typical trigeminal neuralgia using three-dimensional computer graphics. The SCA which runs in the medial aspect of the trigeminal nerve compressed predominantly the root entry zone at the distal segment of the caudal loop. Meanwhile, the SCA which runs in the cranial or lateral aspect of the trigeminal nerve compressed predominantly the mid-third portion at the proximal segment of the caudal loop. The site of neurovascular compression differed depending on the shape of the initial segment of SCA. Transposition methods could not be performed in several patients with arch-shaped SCA. Three-dimensional computer graphics revealed different characteristics of the SCA running in trigeminal neuralgia depending on the site of neurovascular compression and shape of the SCA. These differences might affect procedures for microvascular decompression., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Trigeminal neuralgia is an exemplary neuropathic pain condition characterized by paroxysmal electric-shock-like pain. However, up to 50% of patients also experiences concomitant continuous pain. In this neuroimaging study, we aimed to identify the specific anatomical features of trigeminal nerve root in patients with concomitant continuous pain., Methods: We enrolled 73 patients with a definitive diagnosis of classical and idiopathic trigeminal neuralgia and 40 healthy participants. The diagnosis of trigeminal neuralgia was independently confirmed by two clinicians. Patients were grouped as patients with purely paroxysmal pain (45 patients) and patients also with concomitant continuous pain (28 patients). All participants underwent a structured clinical examination and a 3T MRI with sequences dedicated to the anatomical study of the trigeminal nerve root, including volumetric study. Images analysis was independently performed by two investigators, blinded to any clinical data., Results: In most patients with concomitant continuous pain, this type of pain, described as burning, throbbing or aching, manifested at the disease onset. Demographic and clinical variables did not differ between the two groups of patients; the frequency of neurovascular compression and nerve dislocation were similar. Conversely, trigeminal nerve root atrophy was more severe in patients with concomitant continuous pain than in those with purely paroxysmal pain ( p  = 0.006)., Conclusions: Our clinical and neuroimaging study found that in patients with trigeminal neuralgia, concomitant continuous pain was associated with trigeminal nerve root atrophy, therefore suggesting that this type of pain is likely related to axonal loss and abnormal activity in denervated trigeminal second-order neurons.

Background: Trigeminal neuralgia (TN) is a disease accompanied by severe facial pain, which seriously affects the daily life of patients. Acupuncture is widely used by Traditional Chinese Medicine doctors to treat various painful diseases. Acupuncture combined with the treatment of trigeminal neuralgia can increase the analgesic effect and reduce side effects. However, there is still a lack of more quality multi-center clinical controlled trials and comprehensive meta-analysis, and a lack of more comprehensive and stronger evidence-based medical evidence., Methods: The 2 reviewers used the same search strategy to search CNKI, PubMed, Web of Science, Cochrane Library, Scopus, EBSCO, and the search date is until July 19, 2020. Two people read the retrieved literatures independently, and then delete duplications. Then, use the "risk of bias" tool in Cochrane Handbook 5.2 to score. Only documents with a score greater than 5 can be included. Make a table of literature characteristics, extract baseline patient data, research methods and possible risks of bias in the literature, interventions in treatment and control groups, outcome evaluation indicators (BNI, VAS, ER and AE), and research funding support. Use Review Manager 5.3.5 for meta-analysis, use Stata 15 for regression analysis to find the source of heterogeneity, and then perform subgroup analysis to resolve the heterogeneity based on the corresponding source., Results: The analysis of BNI, VAS, ER and AE data can provide high-quality evidence for high-quality synthesis and/or descriptive analysis of the effectiveness and safety of acupuncture treatment of various causes of urinary retention., Conclusion: This study can provide more comprehensive and strong evidence to prove whether acupuncture is effective and safe in the treatment of TN patients., Registration: The research has been registered and approved on the PROSPERO website. The registration number is CRD42019119606.

Venous malformation (VM) in the posterior cranial fossa occasionally cause trigeminal neuralgia (TN), which were treated with microvascular decompression of its drainer, whereas it was effective only in the limited cases, and its pathological mechanism causing TN is controversial. A 72-year-old man had a 20-year history of typical but severe TN in his left face. Without radiographic evidence of vascular compression on the root entry zone (REZ) of the trigeminal nerve, he underwent stereotactic radiosurgery in previous hospital, resulting in only temporary improvement. On T1-wighted magnetic resonance image with enhancement, the left trigeminal nerve was focally enhanced, which was typical finding after high dose irradiation for TN. Simultaneously, it disclosed small "caput medusa" within the pontine tegmentum, indicated existence of VM in brachium pontis. A 3-dimensional computer graphics model created by fusion of magnetic resonance angiography, diffusion tensor tractography, and fast imaging employing steady-state acquisition elucidated VM was located in the trigeminal nucleus of brachium pontis, which will be very useful for understanding the anatomic correlation of VM and pontine trigeminal nucleus. Since there was no vascular compression at the REZ of the trigeminal nerve, microvascular decompression was not indicated. With minimum dose of gabapentine and carbamazepin, his facial pain completely disappeared and controlled for more than 5 years., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Many medically-refractory trigeminal neuralgia patients are non-responders to surgical treatment. Few studies have explored how trigeminal nerve characteristics relate to surgical outcome, and none have investigated the relationship between subcortical brain structure and treatment outcomes., Methods: We retrospectively studied trigeminal neuralgia patients undergoing surgical treatment with microvascular decompression. Preoperative magnetic resonance imaging was used for manual tracing of trigeminal nerves and automated segmentation of hippocampus, amygdala, and thalamus. Nerve and subcortical structure volumes were compared between responders and non-responders and assessed for ability to predict postoperative pain outcome., Results: In all, 359 trigeminal neuralgia patients treated surgically from 2005-2018 were identified. A total of 34 patients met the inclusion criteria (32 with classic and two with idiopathic trigeminal neuralgia). Across all patients, thalamus volume was reduced ipsilateral compared to contralateral to the side of pain. Between responders and non-responders, non-responders exhibited larger contralateral trigeminal nerve volume, and larger ipsilateral and contralateral hippocampus volume. Through receiver-operator characteristic curve analyses, contralateral hippocampus volume correctly classified treatment outcome in 82% of cases (91% sensitive, 78% specific, p  = 0.008), and contralateral nerve volume correctly classified 81% of cases (91% sensitive, 75% specific, p  < 0.001). Binomial logistic regression analysis showed that contralateral hippocampus and contralateral nerve volumes together classified outcome with 84% accuracy (Nagelkerke R 2  = 65.1)., Conclusion: Preoperative hippocampal and trigeminal nerve volume, measured on standard clinical magnetic resonance images, may predict early non-response to surgical treatment for trigeminal neuralgia. Treatment resistance in medically refractory trigeminal neuralgia may depend on the structural features of both the trigeminal nerve and structures involved in limbic components of chronic pain.

In recent decades, a growing number of structural neuroimaging studies of grey matter (GM) in trigeminal neuralgia (TN) have reported inconsistent alterations. We carried out a systematic review and meta-analysis to identify consistent and replicable GM volume abnormalities using effect-size signed differential mapping (ES-SDM). Furthermore, we conducted a meta-regression to explore the potential effects of clinical characteristics on GM volume alterations in patients with TN. A total of 13 studies with 15 datasets, representing 407 TN patients and 376 healthy individuals, were included in the present study. The results revealed that TN patients had GM volume abnormalities mainly in the basal ganglia, including the putamen, nucleus accumbens (NAc), caudate nucleus and amygdala, as well as the cingulate cortex (CC), thalamus, insula and superior temporal gyrus (STG). The meta-regression analysis showed that verbal rating scale (VRS) scores were negatively correlated with decreased GM volume in the left striatum and that illness duration was negatively correlated with decreased GM volume in the left STG and left insula. These results provide a thorough profile of GM volume alterations in TN patients and constitute robust evidence that aberrant GM volumes in the brain regions regulating and moderating sensory-motor and affective processing may play an important role in the pathophysiology of TN., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Trigeminal neuralgia is a common neuropathic pain in the head and face. The pathogenesis of trigeminal neuralgia is complex, and so far, the pathogenesis of trigeminal neuralgia involving peripheral and central nervous inflammation theory has not been explained clearly. The loss of dopamine neurons in striatum may play an important role in the development of trigeminal nerve, but the reason is not clear. C-Abl is a nonreceptor tyrosine kinase, which can be activated abnormally in the environment of neuroinflammation and cause neuron death. We found that in the rat model of infraorbital nerve ligation trigeminal neuralgia, the pain threshold decreased, the expression of c-Abl increased significantly, the downstream activation product p38 was also activated abnormally and the loss of dopamine neurons in striatum increased. When treated with imatinib mesylate (STI571), a specific c-Abl family kinase inhibitor, the p38 expression was decreased and the loss of dopaminergic neurons was reduced. The mechanical pain threshold of rats was also improved. In conclusion, c-abl-p38 signaling pathway may play an important role in the pathogenesis of trigeminal neuralgia, and it is one of the potential targets for the treatment of trigeminal neuralgia.

Schwann cells are components of the peripheral nerve myelin sheath, which supports and nourishes axons. Upon injury of the trigeminal nerve, Schwann cells are activated and cause trigeminal neuralgia by engulfing the myelin sheath and secreting various neurotrophic factors. Further, Schwann cells can repair the damaged nerve and thus alleviate trigeminal neuralgia. Here, we briefly describe the development and activation of Schwann cells after nerve injury. Moreover, we expound on the occurrence, regulation, and treatment of trigeminal neuralgia; further, we point out the current research deficiencies and future research directions.

Aim: To evaluate the relationship between trigeminal neuralgia (TN) and potential magnetic resonance imaging (MRI)-related measurements in patients with TN., Material and Methods: Retrospective analysis of 104 patients with TN was performed. MRI studies of 98 healthy controls were included in the study to compare the parameters with TN patients’ measurements. MRI measurements of cerebellopontine cistern (CPC) cross-sectional area, trigeminal-pontine angle (TPA) width, and trigeminal nerve cisternal segment length and thickness were assessed on both symptomatic and asymptomatic sides using 1.5T MRI with constructive interference in steady-state sequences. The images were interpreted by two radiologists blinded to the affected sides of the patients., Results: There were significant differences between the symptomatic and asymptomatic sides in terms of mean trigeminal nerve length (8.8 ± 2.34 mm vs. 9.39 ± 2.29 mm; respectively, p=0.001) and thickness (20.9 ± 9.6 mm2 vs. 25 ± 9.98 mm2, respectively; p < 0.001). The median cerebellopontine cistern cross-sectional area was considerably lower on the symptomatic side compared with the asymptomatic side [201 mm2 (interquartile range=93) vs. 224.5 mm2 (interquartile range=77), respectively; p < 0.001]. There were no significant differences between the trigeminal-pontine angle width on either side (38.32 ± 10.38 vs. 38.78 ± 10.9, respectively; p=0.679). There were no statistically significant differences between the right and left sides regarding these parameters in the control group., Conclusion: Smaller CPC cross-sectional area, trigeminal nerve length, and trigeminal nerve thickness on MRI were demonstrated to commonly exist on the symptomatic side in patients with TN. We suggest that this narrow space may increase the risk of vascular compression on the nerve.

Background: Trigeminal neuralgia caused by superior cerebellar artery aneurysms (TGN-SCAAs) is a rare event without previous analysis., Objective: To describe the features of TGN-SCAA based on 8 cases (7 from literature +1 illustrative case)., Methods: All cases were thoroughly studied with gathering of their epidemiological, radiological, clinical, therapeutic, and outcome data., Results: The mean age at diagnosis was 61 yr. Gender distribution showed a female predominance (M: F = 2:6). Side distribution had a left dominance (75%). The aneurysms mean size was 15.4 mm (range: 5-27). All 5 proximal SCAAs (SCA-Basilar junction) presented a lateral-posterior projection, while all 3 distal SCAAs (s2 segment) had variable projections but constant direct trigeminal nerve (TN) contact. No hemorrhage occurred. TGN was the clinical onset in all 8 cases. The most frequent pain distribution was V1-2-3 (n = 3), followed by V1-2 (n = 1) and V1 alone (n = 1). Proximal SCAAs caused TGN through direct TN compression (n = 1), third nerve compression (n = 1), cavernous sinus compression (n = 1), or a combination thereof (n = 2). However, all distal SCAAs caused TGN by direct TN compression (n = 3). Two different treatment options were used: clipping (n = 4) and coiling (n = 4). The post-treatment Barrow Neurological Institute score for pain control was I in all cases (100%). The mRS score was 0 in 75% of cases., Conclusion: TGN-SCAAs are infrequent lesions, characterized by large size, variable TGN mechanisms depending on their anatomic location, and mostly affecting the first and second trigeminal divisions. Both SCAA clipping and coiling were used equally, providing good neurological and pain relief results., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background: Morphological and microstructural changes of the trigeminal nerve due to neurovascular compression (NVC) have been reported in primary trigeminal neuralgia (PTN) patients. This investigation was to examine the relationship between the trigeminal-pontine angle and nerve microstructural changes., Methods: Twenty-five patients underwent microvascular decompression (MVD) for trigeminal neuralgia, and 25 age- and sex-matched controls were studied. The two groups underwent high-resolution three-dimensional MRI and diffusion tensor imaging (DTI). Bilateral trigeminal-pontine angle, cross-sectional area of cerebellopontine angle (CPA) cistern, and the length of trigeminal nerve were evaluated. The mean values of fractional anisotropy and apparent diffusion coefficient at the site of NVC were also measured. Correlation analyses were performed for the trigeminal-pontine angle and the diffusion metrics (FA and ADC) in PTN patients., Results: The mean trigeminal-pontine angle and FA value on the affected side was significantly smaller than the unaffected side and the control group (p < 0.001), while the mean ADC value was significantly increased (p < 0.01). When taking the conflicting vessel types into consideration, the angle affected by the superior cerebellar artery (SCA) was statistically sharper than when affected by other vessels (p < 0.01). However, there were no significant changes in the area of the CPA cistern or the length of the trigeminal nerve between the groups. Correlation analyses showed that the trigeminal-pontine angle was positively correlated with FA and negatively correlated with ADC., Conclusions: A sharp trigeminal-pontine angle may increase the chance of NVC and exacerbate nerve degeneration, which may be one of the supplementary factors that contribute to the pathogenesis of trigeminal neuralgia.

Background: Thalamic pain is a neuropathic pain syndrome that occurs as a result of thalamic damage. It is difficult to develop therapeutic interventions for thalamic pain because its mechanism is unclear. To better understand the pathophysiological basis of thalamic pain, we developed and characterized a new rat model of thalamic pain using a technique of microinjecting cobra venom into the ventral posterolateral nucleus (VPL) of the thalamus., Objectives: This study will establish a new thalamic pain rat model produced by administration of cobra venom to the unilateral ventral posterolateral nucleus., Study Design: This study used an experimental design in rats., Setting: The research took place in the laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine., Methods: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the left VPL. The development of mechanical hyperalgesia and changes in pain-related behaviors and motor function were measured after intrathalamic cobra venom microinjection using the von Frey test, video recording, and cylinder test, respectively. On postoperative days 7 to 35, both electroacupuncture and pregabalin (PGB) were administered to verify that the model reproduced the findings in humans. Moreover, the organizational and structural alterations of the thalamus were examined via transmission electron microscopy (TEM)., Results: The threshold for mechanical stimuli in the left facial skin was significantly decreased on day 3 after thalamic pain modeling as compared with pre-venom treatment. Furthermore, the ultrastructural alterations of neurons such as indented neuronal nuclei, damaged mitochondria and endoplasmic reticulum, and dissolved surrounding tissues were observed under TEM. Moreover, electroacupuncture treatment ameliorated mechanical hyperalgesia, pain-like behaviors, and motor dysfunction, as well as restore normal structures of neurons in the thalamic pain rat model. However, no such beneficial effects were noted when PGB was administered., Limitations: The pathophysiological features were different from the present model and the patients in clinical practice (in most cases strokes, either ischemic or hemorrhagic)., Conclusion: The cobra venom model may provide a reasonable model for investigating the mechanism of thalamic pain and for testing therapies targeting recovery and pain after thalamic lesions., Key Words: Thalamic pain, cobra venom, electroacupuncture, pregabalin, indented neuronal nuclei, damaged mitochondria, dissolved endoplasmic reticulum, golgi body.

Purpose: To describe the anatomical measurements of the trigeminal nerve in patients with trigeminal neuralgia (TN) during Linac (linear accelerator)-based stereotactic radiosurgery (SRS) simulation, targeting the root entry zone (REZ), with a 30% isodose line tangential to the pons, using 4-mm and 6-mm collimators., Methods: In this retrospective study, 53 TN patients, who underwent Fiesta sequence scanning prior to any treatment modality, were assessed. Bilateral measurements were obtained from the cisternal segment of the trigeminal nerve, the trigeminal-pontine angle, and the lateral width of the pontine cistern on the Fiesta MRI sequence. Linac-based SRS simulations were estimated with a radiation dosage of 90Gy to 30% isodose line tangential to the pons, with both 4- and 6-mm collimators. Distances from the calculated targets to the pons and the Gasserian ganglion were measured for later analysis. The statistical analysis was performed comparing the affected side against the unaffected side., Results: Right trigeminal nerve was affected in 36 patients (67.9%), and left one in 17 (32.1%) patients. The mean length of the trigeminal nerve was 9.8mm (range: 4.6-16.8mm) on the affected side, and 10.5mm (range: 5.6-18.4mm) on the unaffected side (p=.02). The mean trigeminal-pontine angle was 12.5° (range: 5.4° to 19.5°) on the affected side, and 10.2° (range: 5.0° to 30.5°) on the unaffected side (p=.01). In the simulations, the distances from the estimated targets to the pons and the Gasserian ganglion were not statistically different between sides. The variation of target-pons and target-ganglion distances was statistically significant on the affected side with the change of collimators (p<.001)., Conclusions: In this anatomical study, significant differences were identified in the length of the affected trigeminal nerve and trigeminal-pontine angle compared to the unaffected side in TN patients in Fiesta sequences prior to surgery or radiosurgery. Significant variation of the target location was found on the REZ between the 4- and 6-collimators during the Linac-based SRS simulations with the estimated radiation dosage of 90Gy and 30% isodose line tangential to the pons., (Copyright © 2018 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

Patients with persistent or recurrent trigeminal neuralgia (TN) after microvascular decompression (MVD) are frequently difficult to manage. This study aimed to analyze the safety and efficiency of repeat MVD, with the main focus on prognostic factors and long-term outcomes.We performed a retrospective study of 41 TN patients (19 men, 22 women) who underwent repeat MVD due to persistent or recurrent pain from January 2008 to January 2016. These patients were followed up from 12 to 96 months (mean, 42 ± 17.3 months). Univariate analysis by Spearman's rank correlation coefficient was used for analysis of prognostic factors.During the repeat MVD, compression of the trigeminal nerve was noted by an artery in 15 patients (36.6%), vein in 6 patients (14.6%), Teflon in 8 patients (19.5%), and no compression in 12 patients (29.3%). Twenty-one patients (51.2%) had already undergone 1 or more previous ablative procedures, either before the first MVD or between the surgeries. The complete pain relief rates of repeat MVD were 87.8% immediately after surgery and 75% at last follow-up. Thirteen patients (31.7%) had new or increased facial numbness after repeat surgery. Univariate analysis revealed 2 prognostic factors, negative finding during reoperation (P = .021) and no pain relief after the initial surgery (P = .038), that showed a negative influence on success rates after repeat MVD.Repeat MVD can still achieve an excellent outcome in patients with persistent or recurrent pain. However, the risk of facial numbness is increased. Surgeons should be selective in performing repeat MVD, priority should be given to patients who have a pain-free interval after initial MVD or show demonstrable compression on imaging studies.

Background: Trigeminal neuralgia (TN) is characterized by facial pain that may be sudden, intense, and recurrent. Neurosurgical interventions, such as radiofrequency rhizotomy, can relieve TN pain, but their mechanisms and effects are unknown. The aim of the present study was to investigate the microstructural tissue changes of the trigeminal nerve (TGN) in patients with TN after they underwent radiofrequency rhizotomy., Methods: Thirty-seven patients with TN were recruited, and diffusion tensor imaging was obtained before and two weeks after radiofrequency rhizotomy. By manually selecting the cisternal segment of the TGN, we measured the volume of the TGN, fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). The TGN volume and mean value of the DTI metrics of the post-rhizotomy lesion side were compared with those of the normal side and those of the pre-rhizotomy lesion side, and they were correlated to the post-rhizotomy visual analogue scale (VAS) pain scores after a one-year follow-up., Results: The alterations before and after rhizotomy showed a significantly increased TGN volume and FA, and a decreased ADC, AD, and RD. The post-rhizotomy lesion side showed a significantly decreased TGN volume, FA, and AD compared with the normal side; however, no significant difference in the ADC and RD were found between the groups. The TGN volume was significantly higher in the non-responders than in the responders (P = 0.016)., Conclusion: Our results may reflect that the effects of radiofrequency rhizotomy in TN patients include axonal damage with perineural edema and that prolonged swelling associated with recurrence might be predicted by MRI images. Further studies are necessary to understand how DTI metrics can quantitatively represent the pathophysiology of TN and to examine the application of DTI in the treatment of TN.

Background: Recent neuroimaging studies have reported grey matter alterations in primary trigeminal neuralgia patients. However, few studies have focused on quantitative measurements of trigeminal nerves and the interaction between trigeminal nerve volume and brain morphology, particularly grey matter volume. In this study, we investigated the link between trigeminal nerves and grey matter volume changes in primary trigeminal neuralgia patients compared to healthy controls. Moreover, we explored the association of structure of trigeminal nerves and grey matter to collected pain clinical variables., Methods: Eighty participants (40 patients and 40 controls) were recruited for the study. All participants underwent MRI sessions and clinical pain assessment. Trigeminal nerve volume and whole brain grey matter volume were evaluated using quantitative imaging techniques. Sensory and affective pain rating indices were assessed using the visual analog scale and short-form McGill Pain Questionnaire. Mediation analysis was conducted to investigate the relationship between clinical pain variables and volumetric changes in trigeminal nerves and grey matter., Results: Decreased trigeminal nerve volume was detected in primary trigeminal neuralgia patients compared to controls. Additionally, reduced grey matter volume was found in several regions associated with pain in primary trigeminal neuralgia subjects, including the insula, secondary somatosensory cortex, hippocampus, dorsal anterior cingulate cortex, precuneus, and several areas of the temporal lobe. Mediation analysis revealed that decreased trigeminal nerve volume drove grey matter volume abnormality of the left insula, and further led to increased pain ratings., Conclusion: This study showed a predominantly direct effect of trigeminal nerve atrophy on clinical pain variables in primary trigeminal neuralgia patients, providing new insight into the pathophysiology of the disease., Trial Registration: ClinicalTrials.gov ID: NCT02713646.

Background: An epidermoid cyst is a rare tumor of the cerebellopontine angle region. It usually presents with ipsilateral compressive symptoms. The contralateral trigeminal neuralgia is an unusual presentation in such cases. We did not find such case reports in the literature., Case Description: Here, we report a case of a 62-year-old female with a right cerebellopontine angle epidermoid cyst presenting with right hearing impairment and the contralateral trigeminal neuralgia., Conclusion: The possible mechanism leading to the contralateral trigeminal neuralgia is discussed here along with the diagnosis and management of the case., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Trigeminal Neuralgia (TN) is a chronic neuropathic pain syndrome characterized by paroxysmal unilateral shock-like pains in the trigeminal territory most frequently attributed to neurovascular compression of the trigeminal nerve at its root entry zone. Recent advances in the study of TN suggest a possible central nervous system (CNS) role in modulation and maintenance of pain. TN and other chronic pain patients commonly experience alterations in cognition and affect, as well as abnormalities in CNS volume and microstructure in regions associated with pain perception, emotional modulation, and memory consolidation. However, the microstructural changes in the hippocampus, an important structure within the limbic system, have not been previously studied in TN patients. Here, we use grey matter analysis to assess whether TN pain is associated with altered hippocampal subfield volume in patients with classic TN. Anatomical magnetic resonance (MR) images of twenty-two right-sided TN patients and matched healthy controls underwent automated segmentation of hippocampal subfields using FreeSurfer v6.0. Right-sided TN patients had significant volumetric reductions in ipsilateral cornu ammois 1 (CA1), CA4, dentate gyrus, molecular layer, and hippocampus-amygdala transition area - resulting in decreased whole ipsilateral hippocampal volume, compared to healthy controls. Overall, we demonstrate selective hippocampal subfield volume reduction in patients with classic TN. These changes occur in subfields implicated as neural circuits for chronic pain processing. Selective subfield volume reduction suggests aberrant processes and circuitry reorganization, which may contribute to development and/or maintenance of TN symptoms., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The trigeminal root entry zone (TREZ) is a transitional zone between the central nervous system (CNS) and peripheral nervous system (PNS), adjacent to the brainstem. Microvascular compression of the TREZ has been considered to be the primary etiology in most cases of trigeminal neuralgia (TN), but whether epigenetic regulation is involved in the pathogenesis of TN is still unclear. Therefore, this study was designed to investigate the epigenetic regulation of histone H3 acetylation in the TREZ in an animal model of TN., Methods: An animal model of TN was established, and adult male Sprague-Dawley rats were randomly assigned to a TN group with trigeminal nerve root compression, sham operation group, TN+HDACi group (TN plus selective histone deacetylase inhibitor injection into the TREZ), or TN+Veh group (TN plus vehicle injection into the TREZ). To measure the length of the central portion of the TREZ from the junction of the trigeminal nerve root entering the pons to the interface of the dome-shaped CNS-PNS transitional zone, immunofluorescent staining of glia and glial nuclei was performed using glial fibrillary acidic protein (GFAP) antibody and DAPI, respectively. To investigate the acetylation of histone H3 within the TREZ in a TN animal model group and a sham operation group, localization of histone H3K9, H3K18, and H3K27 acetylation was examined via immunohistochemical staining methods., Results: Measurements of the CNS-PNS transitional zone in the TREZ revealed that the average length from the junction of the trigeminal nerve root connecting the pons to the glial fringe of the TREZ in the TN group was longer than that in the sham operation group (p < 0.05) and that the interface gradually migrated distally. Cells that stained positive for acetylated histone H3K9, H3K18, and H3K27 were distributed around both sides of the border of the CNS-PNS junction in the TREZ. The ratio of immunoreactive H3K9-, H3K18- and H3K27-positive cells in the TN group was obviously higher than that in the sham operation group on postoperative days 7, 14, 21, and 28 (p < 0.05)., Conclusions: These results suggested that chronic compression of the trigeminal nerve root may be involved in the pathogenesis of TN in an animal model by influencing the plasticity of the CNS-PNS transitional zone and the level of histone acetylation in the TREZ.

The authors report the case of a 52-year-old man who presented with rapid-onset lancinating facial pain consistent with trigeminal neuralgia. Magnetic resonance imaging revealed a nonenhancing small lesion on the right trigeminal nerve concerning for an atypical schwannoma or neuroma. The patient underwent resection of the mass via a right retrosigmoid approach. His facial pain completely resolved immediately postoperatively and had not recurred at 6 months after surgery. The mass was consistent with normal brain tissue (neurons and glial cells) without evidence of mitoses. A final histopathological diagnosis of ectopic brain tissue with neural tissue demonstrating focal, chronic T-cell inflammation was made. The partial rhizotomy during resection was curative for the facial pain. To the authors' knowledge, this is the first report of neuroglial ectopia causing trigeminal neuralgia.

Trigeminal neuralgia (TN) is a severe form of chronic facial neuropathic pain. Increasing interest in the neuroimaging of pain has highlighted changes in the root entry zone in TN, but also group-level central nervous system gray and white matter (WM) abnormalities. Group differences in neuroimaging data are frequently evaluated with univariate statistics; however, this approach is limited because it is based on single, or clusters of, voxels. By contrast, multivariate pattern analyses consider all the model's neuroanatomical features to capture a specific distributed spatial pattern. This approach has potential use as a prediction tool at the individual level. We hypothesized that a multivariate pattern classification method can distinguish specific patterns of abnormal WM connectivity of classic TN from healthy controls (HCs). Diffusion-weighted scans in 23 right-sided TN and matched controls were processed to extract whole-brain interregional streamlines. We used a linear support vector machine algorithm to differentiate interregional normalized streamline count between TN and HC. This algorithm successfully differentiated between TN and HC with an accuracy of 88%. The structural pattern emphasized WM connectivity of regions that subserve sensory, affective, and cognitive dimensions of pain, including the insula, precuneus, inferior and superior parietal lobules, and inferior and medial orbital frontal gyri. Normalized streamline counts were associated with longer pain duration and WM metric abnormality between the connections. This study demonstrates that machine-learning algorithms can detect characteristic patterns of structural alterations in TN and highlights the role of structural brain imaging for identification of neuroanatomical features associated with neuropathic pain disorders.

The cingulate cortex (CC) is a brain region that plays a key role in pain processing, but CC abnormalities are not unclear in patients with trigeminal neuralgia (TN). The purpose of this study was to determine the central causal mechanisms of TN and the surrounding brain structure in healthy controls and patients with TN using 7 Tesla (T) magnetic resonance imaging (MRI). Whole-brain parcellation in gray matter volume and thickness was assessed in 15 patients with TN and 16 healthy controls matched for sex, age, and regional variability using T1-weighted imaging. Regions of interest (ROIs) were measured in rostral anterior CC (rACC), caudal anterior CC (cACC) and posterior CC (PCC). We also investigated associations between gray matter volume or thickness and clinical symptoms, such as pain duration, Barrow Neurologic Institute (BNI) scores, offender vessel, and medications, in patients with TN. The cACC and PCC exhibited gray matter atrophy and reduced thickness between the TN and control groups. However, the rACC did not. Cortical volumes were negatively correlated with pain duration in transverse and inferior temporal areas, and thickness was also negatively correlated with pain duration in superior frontal and parietal areas. The cACC and PCC gray matter atrophy occurred in the patients with TN, and pain duration was associated with frontal, parietal, and temporal cortical regions. These results suggest that the cACC, PCC but not the rACC are associated with central pain mechanisms in TN., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Trigeminal neuralgia (TN) is a severe unilateral facial pain involving 1 or more branches of the trigeminal nerve (CNV). Microvascular decompression is a standard curative treatment of pharmacoresistant classic TN. Alternative procedures used for secondary or idiopathic TN usually lead to a high rate of pain recurrence and sensitive deficits. Partial sensory rhizotomy (PSR) is one of these ablative procedures. However, the lack of anatomic knowledge about the somatotopy of CNV lead to variable results in pain relief and hypoesthesia., Objective: To refine the somatotopy of CNV and bring new anatomic landmarks for PSR, studying a cohort of patients treated by a targeted PSR (TPSR)., Methods: Retrospective and consecutive cases of adult patients treated in our institution between March 2000 and June 2015 for pharmacoresistant TN without vascular compression were collected. Our surgical procedure was performed using a precision map of the somatotopy of CNV. We compared our results with other surgical and nonsurgical therapies., Results: Twenty-two patients had undergone TPSR. Fourteen had an idiopathic TN without compression of the nerve root, 6 had a secondary TN caused by multiple sclerosis, and 2 had a trigeminal conflict by inoperable tumor. Complete pain relief was achieved in 86.4% of the patients. Postoperative hypoesthesia was partial and focalized (22.7%). TN recurrence rate at 5 years was 31.5% (standard deviation, 10.9%)., Conclusions: We clarified the functional somatotopy of CNV in its juxtapontine portion. TPSR is an interesting alternative to other ablative procedures to treat pharmacoresistant TN without vascular compression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

OBJECTIVE Walter E. Dandy described for the first time the anatomical course of the superior petrosal vein (SPV) and its significance during surgery for trigeminal neuralgia. The patient's safety after sacrifice of this vein is a challenging question, with conflicting views in current literature. The aim of this systematic review was to analyze the current surgical considerations regarding Dandy's vein, as well as provide a concise review of the complications after its obliteration. METHODS A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A thorough literature search was conducted on PubMed, Web of Science, and the Cochrane database; articles were selected systematically based on the PRISMA protocol and reviewed completely, and then relevant data were summarized and discussed. RESULTS A total of 35 publications pertaining to the SPV were included and reviewed. Although certain studies report almost negligible complications of SPV sectioning, there are reports demonstrating the deleterious effects of SPV obliteration when achieving adequate exposure in surgical pathologies like trigeminal neuralgia, vestibular schwannoma, and petroclival meningioma. The incidence of complications after SPV sacrifice (32/50 cases in the authors' series) is 2/32 (6.2%), and that reported in various case series varies from 0.01% to 31%. It includes hemorrhagic and nonhemorrhagic venous infarction of the cerebellum, sigmoid thrombosis, cerebellar hemorrhage, midbrain and pontine infarct, intracerebral hematoma, cerebellar and brainstem edema, acute hydrocephalus, peduncular hallucinosis, hearing loss, facial nerve palsy, coma, and even death. In many studies, the difference in incidence of complications between the SPV-sacrificed group and the SPV-preserved group was significant. CONCLUSIONS The preservation of Dandy's vein is a neurosurgical dilemma. Literature review and experiences from large series suggest that obliterating the vein of Dandy while approaching the superior cerebellopontine angle corridor may be associated with negligible complications. However, the counterview cannot be neglected in light of some series showing an up to 30% complication rate from SPV sacrifice. This review provides the insight that although the incidence of complications due to SPV obliteration is low, they can happen, and the sequelae might be worse than the natural history of the existing pathology. Therefore, SPV preservation should be attempted to optimize patient outcome.

Background It has been proposed that multiple sclerosis lesions afflicting the pontine trigeminal afferents contribute to trigeminal neuralgia in multiple sclerosis. So far, there are no imaging studies that have evaluated interactions between supratentorial lesions and trigeminal neuralgia in multiple sclerosis patients. Methods We conducted a retrospective study and sought multiple sclerosis patients with trigeminal neuralgia and controls in a local database. Multiple sclerosis lesions were manually outlined and transformed into stereotaxic space. We determined the lesion overlap and performed a voxel-wise subtraction analysis. Secondly, we conducted a voxel-wise non-parametric analysis using the Liebermeister test. Results From 12,210 multiple sclerosis patient records screened, we identified 41 patients with trigeminal neuralgia. The voxel-wise subtraction analysis yielded associations between trigeminal neuralgia and multiple sclerosis lesions in the pontine trigeminal afferents, as well as larger supratentorial lesion clusters in the contralateral insula and hippocampus. The non-parametric statistical analysis using the Liebermeister test yielded similar areas to be associated with multiple sclerosis-related trigeminal neuralgia. Conclusions Our study confirms previous data on associations between multiple sclerosis-related trigeminal neuralgia and pontine lesions, and showed for the first time an association with lesions in the insular region, a region involved in pain processing and endogenous pain modulation.