Deciphering the functional role of insular cortex stratification in trigeminal neuropathic pain.

Trigeminal neuropathic pain (TNP) is a major concern in both dentistry and medicine. The progression from normal to chronic TNP through activation of the insular cortex (IC) is thought to involve several neuroplastic changes in multiple brain regions, resulting in distorted pain perception and associated comorbidities. While the functional changes in the insula are recognized contributors to TNP, the intricate mechanisms underlying the involvement of the insula in TNP processing remain subjects of ongoing investigation. Here, we have overviewed the most recent advancements regarding the functional role of IC in regulating TNP alongside insights into the IC's connectivity with other brain regions implicated in trigeminal pain pathways. In addition, the review examines diverse modulation strategies that target the different parts of the IC, thereby suggesting novel diagnostic and therapeutic management of chronic TNP in the future.

Functional alterations of the brain default mode network and somatosensory system in trigeminal neuralgia.

Mapping the localization of the functional brain regions in trigeminal neuralgia (TN) patients is still lacking. The study aimed to explore the functional brain alterations and influencing factors in TN patients using functional brain imaging techniques. All participants underwent functional brain imaging to collect resting-state brain activity. The significant differences in regional homogeneity (ReHo) and amplitude of low frequency (ALFF) between the TN and control groups were calculated. After familywise error (FWE) correction, the differential brain regions in ReHo values between the two groups were mainly located in bilateral middle frontal gyrus, bilateral inferior cerebellum, right superior orbital frontal gyrus, right postcentral gyrus, left inferior temporal gyrus, left middle temporal gyrus, and left gyrus rectus. The differential brain regions in ALFF values between the two groups were mainly located in the left triangular inferior frontal gyrus, left supplementary motor area, right supramarginal gyrus, and right middle frontal gyrus. With the functional impairment of the central pain area, the active areas controlling memory and emotion also change during the progression of TN. There may be different central mechanisms in TN patients of different sexes, affected sides, and degrees of nerve damage. The exact central mechanisms remain to be elucidated.

Causal interactions in brain networks predict pain levels in trigeminal neuralgia.

Trigeminal neuralgia (TN) is a highly debilitating facial pain condition. Magnetic resonance imaging (MRI) is the main method for generating insights into the central mechanisms of TN pain in humans. Studies have found both structural and functional abnormalities in various brain structures in TN patients as compared with healthy controls. Whereas studies have also examined aberrations in brain networks in TN, no studies have to date investigated causal interactions in these brain networks and related these causal interactions to the levels of TN pain. We recorded fMRI data from 39 TN patients who either rested comfortably in the scanner during the resting state session or tracked their pain levels during the pain tracking session. Applying Granger causality to analyze the data and requiring consistent findings across the two scanning sessions, we found 5 causal interactions, including: (1) Thalamus → dACC, (2) Caudate → Inferior temporal gyrus, (3) Precentral gyrus → Inferior temporal gyrus, (4) Supramarginal gyrus → Inferior temporal gyrus, and (5) Bankssts → Inferior temporal gyrus, that were consistently associated with the levels of pain experienced by the patients. Utilizing these 5 causal interactions as predictor variables and the pain score as the predicted variable in a linear multiple regression model, we found that in both pain tracking and resting state sessions, the model was able to explain ∼36 % of the variance in pain levels, and importantly, the model trained on the 5 causal interaction values from one session was able to predict pain levels using the 5 causal interaction values from the other session, thereby cross-validating the models. These results, obtained by applying novel analytical methods to neuroimaging data, provide important insights into the pathophysiology of TN and could inform future studies aimed at developing innovative therapies for treating TN.

Risk factors associated with trigeminocardiac reflex in patients with trigeminal neuralgia during percutaneous balloon compression: A retrospective cohort study.

BACKGROUND: The trigeminocardiac reflex (TCR) is a brainstem reflex commonly elicited during percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia (TN), which is characterized by drastic hemodynamic disturbances, such as bradycardia, arrhythmias and even cardiac arrest. In order to prevent catastrophic consequences, it is vital to screen the risk factors of TCR during perioperative period. The primary purpose of this study was to identify potential risk factors associated with TCR in patients with TN undergoing PBC, and to summarize the enlightenment of clinical anesthesia management. METHODS: The clinical data of 165 patients diagnosed with TN undergoing PBC from January 2021 to December 2021 were retrospectively analyzed. TCR was defined as a sudden decrease in heart rate of 20% or more compared with baseline, and / or cardiac arrest, coinciding with the stimulus of any branch of the trigeminal nerve. And a clear cause-effect relationship between heart rate reduction and PBC-related intervention was required. All demographic characteristics as well as surgical and anesthetic data were compared between TCR group and TCR-free group. Univariate and multivariate logistic regression analysis were used to further analyze TCR-related risk factors. RESULTS: Of the 165 patients enrolled in this study, 73 (44.2%) were male and 92 (55.8%) were female, and the average age was 64.22 ± 9.72 years. The incidence of TCR in the patients with TN during PBC was 54.5%. The results of multivariate regression analysis indicated that the risk factor for TCR was heart rate < 60 beats/min immediately before foramen ovale puncture (OR: 4.622; 95%CI: 1.470-14.531; P < 0.05). CONCLUSION: Heart rate < 60 beats/min immediately before foramen ovale puncture was independently associated with TCR. Therefore, it is necessary for anesthesiologists to raise heart rate appropriately to prevent TCR during PBC.

Predictive and prognostic factors for outcome of microvascular decompression in trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is a disease characterized by recurring, short-lived, electric shock-like pain experienced on one side of the face. Microvascular decompression (MVD) is one of the most effective surgical interventions for resolving TN caused by neurovascular compression. This study aimed to determine the predictive and prognostic factors of surgical outcomes. METHODS: This retrospective cohort study enrolled patients diagnosed with TN who underwent MVD at our hospital during 2013-2019. The demographic information, pain character, peri-operative Barrow Neurological Institute (BNI) scale, medication, operative finding were recorded. And the outcome was Outcomes were divided into drug-free and drug-dependent group. Predisposing factors for each outcome were analyzed by one-way analysis of variance, followed by a Mann-Whitney U test or Kruskal-Wallis test. RESULTS: A total of 104 consecutive patients received MVD to treat TN, and 88 patients were enrolled in this study. The overall postoperative drug-free outcome was 72.7%. A significant difference in drug-free outcomes was observed for patients with typical TN (80.8%) compared with patients with atypical TN (33.33%, p = 0001). When severe venous compression was encountered during MVD, the drug-free outcome fell to 50% (10/20, p = 0.009). The Mann-Whitney U test indicated typical TN as a positive predictive factor of a drug-free outcome, whereas severe venous compression was a negative predictive factor. The patients with preoperative BNI score of 4 had better improvement than others (p = 0.045). Age, onset duration, and arterial loop had no specific difference in this study. CONCLUSION: In our study, atypical TN and severe venous compression were associated with poor outcomes. Regrouping atypical TN into precise diagnosis represents an immediate priority according to our result. The preoperative BNI score could be used as an effective predictive tool for the outcome of MVD surgery.

Activation of parabrachial nucleus - ventral tegmental area pathway underlies the comorbid depression in chronic neuropathic pain in mice.

Depression symptoms are often found in patients suffering from chronic pain, a phenomenon that is yet to be understood mechanistically. Here, we systematically investigate the cellular mechanisms and circuits underlying the chronic-pain-induced depression behavior. We show that the development of chronic pain is accompanied by depressive-like behaviors in a mouse model of trigeminal neuralgia. In parallel, we observe increased activity of the dopaminergic (DA) neuron in the midbrain ventral tegmental area (VTA), and inhibition of this elevated VTA DA neuron activity reverses the behavioral manifestations of depression. Further studies establish a pathway of glutamatergic projections from the spinal trigeminal subnucleus caudalis (Sp5C) to the lateral parabrachial nucleus (LPBN) and then to the VTA. These glutamatergic projections form a direct circuit that controls the development of the depression-like behavior under the state of the chronic neuropathic pain.

Characteristics and natural disease history of persistent idiopathic facial pain, trigeminal neuralgia, and neuropathic facial pain.

OBJECTIVE: This study aimed to characterize key features, and to assess the clinical development of common nondental facial pain syndromes such as persistent idiopathic facial pain (PIFP), trigeminal neuralgia (TN), and neuropathic facial pain (NEUROP). METHODS: This is a longitudinal study in which prospective questionnaire data of patients presenting to a specialized outpatient clinic were collected from 2009 to 2019. A telephone interview was conducted with the same patients in 2020 to assess the natural disease history. RESULTS: n = 411 data sets of patients with chronic facial pain were compiled. Among these were n = 150 patients with PIFP, n = 111 patients with TN, and n = 86 patients with NEUROP. Guideline therapy had not been initiated in 38.7% (58/150; PIFP), 19.8% (22/111; TN), and 33.7% (29/86; NEUROP) patients. Of the patients with PIFP, 99.3% (149/150) had primarily consulted a dentist due to their pain syndrome. The additional telephone interview was completed by 236 out of the 411 patients (57.4%). Dental interventions in healthy teeth had been performed with the intention to treat the pain in many patients (78/94 [83.0%] PIFP; 34/62 [54.8%] TN; 19/43 [44.2%] NEUROP), including dental extractions. 11.3% (7/43) of the patients with TN had never profited from any therapy. In contrast, 29.8% (28/94) of the patients with PIFP had never profited from any therapy. Furthermore, the primary pharmaceutical therapy options suggested by national guidelines were, depending on the substance class, only considered to be effective by 13.8% (13/94; antidepressants) and 14.9% (14/94; anticonvulsants) of the patients with PIFP. CONCLUSIONS: Facial pain syndromes pose a considerable disease burden. Although treatment of TN seems to be effective in most patients, patients with PIFP and NEUROP report poor effectiveness even when following guideline therapy suggestions. In addition, unwarranted dental interventions are common in facial pain syndromes.

Cortical thickness, gyrification and sulcal depth in trigeminal neuralgia.

Neuroimaging studies have documented brain structural alterations induced by chronic pain, particularly in gray matter volume. However, the effects of trigeminal neuralgia (TN), a severe paroxysmal pain disorder, on cortical morphology are not yet known. In this study, we recruited 30 TN patients and 30 age-, and gender-matched healthy controls (HCs). Using Computational Anatomy Toolbox (CAT12), we calculated and compared group differences in cortical thickness, gyrification, and sulcal depth with two-sample t tests (p < 0.05, multiple comparison corrected). Relationships between altered cortical characteristics and pain intensity were investigated with correlation analysis. Compared to HCs, TN patients exhibited significantly decreased cortical thickness in the left inferior frontal, and left medial orbitofrontal cortex; decreased gyrification in the left superior frontal cortex; and decreased sulcal depth in the bilateral superior frontal (extending to anterior cingulate) cortex. In addition, we found significantly negative correlations between the mean cortical thickness in left medial orbitofrontal cortex and pain intensity, and between the mean gyrification in left superior frontal cortex and pain intensity. Chronic pain may be associated with abnormal cortical thickness, gyrification and sulcal depth in trigeminal neuralgia. These morphological changes might contribute to understand the underlying neurobiological mechanism of trigeminal neuralgia.

Stimulating GABAergic Neurons in the Nucleus Accumbens Core Alters the Trigeminal Neuropathic Pain Responses in a Rat Model of Infraorbital Nerve Injury.

The nucleus accumbens core (NAcc) is an important component of brain reward circuitry, but studies have revealed its involvement in pain circuitry also. However, its effect on trigeminal neuralgia (TN) and the mechanism underlying it are yet to be fully understood. Therefore, this study aimed to examine the outcomes of optogenetic stimulation of NAcc GABAergic neurons in an animal model of TN. Animals were allocated into TN, sham, and control groups. TN was generated by infraorbital nerve constriction and the optogenetic virus was injected into the NAcc. In vivo extracellular recordings were acquired from the ventral posteromedial nucleus of the thalamus. Alterations of behavioral responses during stimulation "ON" and "OFF" conditions were evaluated. In vivo microdialysis was performed in the NAcc of TN and sham animals. During optogenetic stimulation, electrophysiological recordings revealed a reduction of both tonic and burst firing activity in TN animals, and significantly improved behavioral responses were observed as well. Microdialysis coupled with liquid chromatography/tandem mass spectrometry analysis revealed significant alterations in extracellular concentration levels of GABA, glutamate, acetylcholine, dopamine, and citrulline in NAcc upon optic stimulation. In fine, our results suggested that NAcc stimulation could modulate the transmission of trigeminal pain signals in the TN animal model.

The diagnostic value of pain evoked potential by electrical stimulation combined with noceciptive blink reflex in trigeminal neuralgia.

Microvascular decompression is the first choice for treating the primary trigeminal neuralgia to provide the most extended duration of pain freedom. However, in microvascular decompression, we found that this kind of operation is only suitable for some patients. It is of great value to objectively judge the function and abnormality of the trigeminal pain conduction pathway in guiding the operation process. This brief report investigates the value of pain evoked potential by electrical stimulation and noceciptive blink reflex in trigeminal neuralgia. We detected the pain evoked potential in 34 patients with trigeminal neuralgia and 48 healthy controls treated by electrical stimulation and blink reflex. We demonstrated no significant differences in the latencies of V1, V2, V3, and R2 of the affected side and the contralateral side in patients with trigeminal neuralgia. The latencies of those four indicators of the affected side in patients with trigeminal neuralgia were notably decreased compared to those on the same side in healthy controls. The receiver operating characteristic curve analysis showed that the area under curve, sensitivity and specificity of the combined diagnosis of latency and amplitude were significantly higher than the single diagnosis. The latency and amplitude of V1 were highly sensitive, while those of V2 was highly specific. Trigeminal neuralgia can be effectively diagnosed by combining pain evoked potential by electrical stimulation and noceciptive blink reflex. The pathogenesis of trigeminal neuralgia should be combined with peripheral pathogenicity and the theory of central pathogenicity.

Early nociceptive evoked potentials (NEPs) recorded from the scalp.

OBJECTIVE: Neurophysiological investigation of nociceptive pathway has so far been limited to late cortical responses. We sought to detect early components of the cortical evoked potentials possibly reflecting primary sensory activity. METHODS: The 150 IDE micropatterned electrode was used to selectively activate Aδ intraepidermic fibres of the right hand dorsum in 25 healthy subjects and 3 patients suffering from trigeminal neuralgia. Neurographic recordings were performed to assess type of stimulated fibres and check selectivity. Cortical evoked potentials were recorded from C3'-Fz and Cz-Au1. RESULTS: Neurographic recordings confirmed selective activation of Aδ fibres. Early components were detected after repetitive stimulation (0.83/s rate and 250-500 averages); the first negative component occured at 40 ms (N40) on the contralateral scalp. CONCLUSIONS: The provided data support the hypothesis that N40 could be the cortical primary response conducted by fast Aδ fibres. SIGNIFICANCE: This is the first report of early, possibly primary, cortical responses in humans by nociceptive peripheral stimulation. Although not perfected yet to allow widespread diagnostic use, this is probably the only method to allow fully objective evaluation of the nociceptive system, with important future implications in experimental and clinical neurophysiology.

The changing face of trigeminal neuralgia-A narrative review.

OBJECTIVE: This narrative review aims to update the reader on the new classification of trigeminal neuralgia (TN), clinical signs, pathophysiologic evidence, and their implications on management. This review is based on the authors' collective experience and knowledge of the literature in addition to a literature search. BACKGROUND: In recent years, the phenotype of TN has been intensively studied leading to discrete groups of patients. These include patients with TN with additional continuous pain, and patients with and without neurovascular compression of the trigeminal dorsal root entry zone. A number of associated clinical signs such as tearing and sensory changes need further research. METHODS: The literature on TN was searched in PubMed with the aims of providing evidence for the recently published third edition of the International Classification of Headache Disorders (ICHD) and update the clinical phenotype and management of the TN subcategories. RESULTS: The ICHD's new classification for TN is based on reliable clinical data, imaging, and neurophysiologic studies. The TN classification reflects current knowledge and has improved the possibility for clinicians to choose adequate management options. However, there is a lack of effective, safe drugs for the management of TN and sparse, robust data on neurosurgical options. CONCLUSION: Research into all aspects of TN-diagnosis, pharmacotherapy, surgery, long-term management prognosis, and natural history-is needed. Research should adhere to the ICHD's schema for TN. Improved drugs are needed along with rigorous research into surgical options and their efficacy for different subtypes of TN.

Assessment of Growth Factors, Cytokines, and Cellular Markers in Saliva of Patients with Trigeminal Neuralgia.

We proposed to perform a comparative analysis of growth factors, cytokines, and chemokine receptors on the salivary cells in the saliva obtained from trigeminal neuralgia (TN) and normal subjects. Saliva was collected from TN and healthy subjects. Salivary cells were isolated by centrifugation. The expression of the cell surface marker was analyzed by flow cytometry. A cytometric bead array was done to measure the levels of cytokines and growth factors on the flow cytometer. Saliva from TN subjects showed lower growth factor levels of Angiopoietin-2, bFGF, HGF, SCF, TGF-α, and VEGF and higher cytokine levels of IL-1ß, TNF-α, CCL2, IL-17A, IL-6, and CXCL8, as well as higher expression levels of chemokine receptors CCR1 (CD191), CR3 (CD11b), CCR2 (CD192), CXCR5 (CD185), and CCR5 (CD196) in the cells from TN saliva. A certain set of cytokines and growth factors in the saliva, as well as chemokine receptors on salivary cells, could be a useful tool in the diagnostics and prognostics of trigeminal neuralgia. Trigeminal neuralgia is one of the significant pathological conditions in the class of chronic diseases around the world. Many targeted approaches are being tried by various research groups to utilize the information of the inflammatory microenvironment to resolve the pathology of chronic TN.

Diffusivity Metrics Three Months After Upfront Gamma Knife Radiosurgery for Trigeminal Neuralgia May Be Correlated with Pain Relief.

BACKGROUND: Gamma Knife radiosurgery (GKRS) is a safe and effective treatment option for trigeminal neuralgia (TN). However, there is no objective, noninvasive tool to identify nonresponders or late responders to GKRS and to facilitate longitudinal patient management. We hypothesized that diffusivity metrics obtained 3 months after GKRS may correlate with response to treatment. METHODS: Sixteen patients with TN treated with GKRS underwent preprocedural and 3-month postprocedural 3-T magnetic resonance imaging of the brain. Diffusion tensor metrics of axial diffusivity, radial diffusivity, and fractional anisotropy were extracted from the pontine segments, the root entry zones, and the distal cisternal segments of both trigeminal nerves. Diffusivity metrics at the 3-month post-GKRS time point were compared with pain relief at last follow-up. Favorable response to GKRS was defined as pain intensity of I-III on the Barrow Neurological Institute scale. RESULTS: The median clinical follow-up was 11 months (range 3-18 months). Patients with favorable response to GKRS at last follow-up had lower mean fractional anisotropy values at the pontine segment (P = 0.04) and increased mean radial diffusivity values at the root entry zones (P = 0.032) of the treated trigeminal nerve on the 3-month diffusion tensor imaging sequences as compared with the nonresponders. CONCLUSIONS: Diffusivity metrics changes on the treated trigeminal nerve at the 3-month time point after GKRS for TN correlated with pain relief at last follow-up. Further, well-designed studies are warranted to establish the clinical application of diffusion tensor imaging as a noninvasive, prognostic tool in patients with TN managed with GKRS.

Internal Neurolysis (Nerve Combing) for Trigeminal Neuralgia without Neurovascular Compression

Objective The aim of the present study was to describe and evaluate the initial and the long-term clinical outcome of internal neurolysis (IN) for trigeminal neuralgia (TN) without neurovascular compression (NVC). Methods A total of 170 patients diagnosed with TN were treated by posterior fossa exploration, during the period between April 2012 and October 2019. The patients were divided into two groups: Group A (50 patients)was treated by IN and Group B (120 patients) received microvascular decompression (MVD). Surgical outcomes and postoperative complications were compared between the two groups. Pain intensity was assessed by the Barrow Neurological Institute (BNI) pain intensity score and BNI facial numbness score. Pain recurrence was statistically evaluated with Kaplan-Meier analysis. Results Pain was completely relieved in 44 patients (88%) who underwent IN (group A); 3 (6%) experienced occasional pain but did not require medication (BNI 2). In group B, 113 (94%) experienced immediate pain relief after MVD. The median duration of follow-ups was 4 years (6 months to 7.5 years). In Group A, there was a meantime recurrence of 27 months in 3 patients (6%). The recurrence in Group B was of 5.8% during the follow-up period. There were no statistically significant differences in the surgical outcomes between the two groups. All patients with IN experienced some degree of numbness, 88% of the cases resolved in 6 months, on average. Conclusion Internal neurolysis is an effective, safe and durable treatment option for trigeminal neuralgia when NVC is absent.

The effect of IL-6/Piezo2 on the trigeminal neuropathic pain.

The nature of trigeminal neuropathic pain (TN) attacks is regarded as the ignition of ectopic action potentials from the trigeminal root following vascular compression, which seemed to be related to transmembrane proteins and inflammation factors. This study focused on the mechanosensitive channel Piezo2 and cytokine IL-6. The chronic constriction injury of infraorbital nerve in SD rats was used to establish the TN model. The trigeminal ganglion was then achieved to perform immunocytochemistry studies. A significant upregulation of Piezo2 and IL-6 was showed in the TN model rats. The Piezo2 positive accounted for 72.3±9.5% in those IL-6 positive neurons. The Piezo2 co-localized with CGRP, IB4 and NF-200 but not with GFAP, which implied that it was expressed in both the C-type and the A-type neurons. After administration of GsMTx4 or anti-rat IL-6 antibody in the TN model, the dynamic allodynia and pinprick hyperalgesia scores as well as the mechanical threshold changed significantly. In the sham-operation rates, with local administration of IL-6, an upregulation of Piezo2 was also exhibited. Our study demonstrated that the up-regulation of Piezo2 in the pain afferent neurons following trigeminal nerve injury may play a role in the development of the neuralgia. Meanwhile, the expression of Piezo2 may be modulated by inflammatory cytokines, such as IL-6.

Transient Receptor Potential (TRP) Ion Channels in Orofacial Pain.

Orofacial pain, including temporomandibular joint disorders pain, trigeminal neuralgia, dental pain, and debilitating headaches, affects millions of Americans each year with significant population health impact. Despite the existence of a large body of information on the subject, the molecular underpinnings of orofacial pain remain elusive. Two decades of research has identified that transient receptor potential (TRP) ion channels play a crucial role in pathological pain. A number of TRP ion channels are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. Although there are many similarities, the orofacial sensory system shows some distinct peripheral and central pain processing and different sensitivities from the spinal sensory system. Relative to the extensive review on TRPs in spinally-mediated pain, the summary of TRPs in trigeminally-mediated pain has not been well-documented. This review focuses on the current experimental evidence involving TRP ion channels, particularly TRPV1, TRPA1, TRPV4, and TRPM8 in orofacial pain, and discusses their possible cellular and molecular mechanisms.

Trigeminal neuralgia in children and adolescents: Experience of a tertiary pediatric headache clinic.

OBJECTIVES: To describe the characteristics and treatment of trigeminal neuralgia in children attending a dedicated pediatric headache clinic. BACKGROUND: Data on trigeminal neuralgia as a cause of headache are largely derived from adult studies. Little is known about the etiology, symptoms, treatment, and outcome of the disorder in children and adolescents. METHODS: A case series study was undertaken. The database of a headache clinic within a tertiary, university-affiliated, pediatric medical center was searched for all patients aged 3-18 years presenting with clinical and epidemiological features of trigeminal neuralgia or trigeminal neuropathy from January 2015 to December 2019. The diagnosis was revised for the present study according to the criteria of the International Classification of Headache Disorders, third edition. Data on demographic parameters, clinical symptoms, treatment, and outcome were collected from the medical files. RESULTS: Of the 1040 patients who presented to our clinic during the study period, five (0.5%) were diagnosed with trigeminal neuralgia. Mean patient age was 15.1 ± 3.0 years (range 9.5-17.5; 95% CI 10.8-18.9). All had idiopathic type: purely paroxysmal in one and with concomitant continuous pain in four. Findings on herpes serology in all five and magnetic resonance imaging were normal in four patients. In the fifth, a vascular ring was noted from the superior cerebellar artery around the right trigeminal nerve without radiologic evidence of vascular nerve compression. All patients were initially treated with carbamazepine: one reported partial relief, two did not respond, and two had severe adverse effects. Three patients were switched to gabapentin but only one responded well. Three patients were treated with nerve block. CONCLUSION: Trigeminal neuralgia accounted for only a small proportion of patients seeking treatment for headache in pediatric headache clinic over a 5-year period. Unlike findings in adults, vascular compression was not the underlying mechanism in any of our patients. The response to pharmacologic treatment was poor. Nerve block may serve as an alternative when pharmacologic treatment fails.

Trigeminal Neuralgia With Extraoral Trigger Zone Successfully Treated With Intraoral Injections of Botulinum Toxin: A Case Report.

Trigeminal neuralgia is a pain condition that is frequently misdiagnosed and challenging to manage. We present the case of a patient with trigeminal neuralgia with multiple misdiagnoses and poorly managed pain. Despite the presence of trigger zones both inside and outside her mouth, complete symptom resolution was ultimately achieved through onabotulinumtoxinA injections, delivered solely intraorally.

Optogenetic stimulation of the motor cortex alleviates neuropathic pain in rats of infraorbital nerve injury with/without CGRP knock-down.

BACKGROUND: Previous studies have reported that electrical stimulation of the motor cortex is effective in reducing trigeminal neuropathic pain; however, the effects of optical motor cortex stimulation remain unclear. OBJECTIVE: The present study aimed to investigate whether optical stimulation of the primary motor cortex can modulate chronic neuropathic pain in rats with infraorbital nerve constriction injury. METHODS: Animals were randomly divided into a trigeminal neuralgia group, a sham group, and a control group. Trigeminal neuropathic pain was generated via constriction of the infraorbital nerve and animals were treated via selective inhibition of calcitonin gene-related peptide in the trigeminal ganglion. We assessed alterations in behavioral responses in the pre-stimulation, stimulation, and post-stimulation conditions. In vivo extracellular recordings were obtained from the ventral posteromedial nucleus of the thalamus, and viral and α-CGRP expression were investigated in the primary motor cortex and trigeminal ganglion, respectively. RESULTS: We found that optogenetic stimulation significantly improved pain behaviors in the trigeminal neuralgia animals and it provided more significant improvement with inhibited α-CGRP state than active α-CGRP state. Electrophysiological recordings revealed decreases in abnormal thalamic firing during the stimulation-on condition. CONCLUSION: Our findings suggest that optical motor cortex stimulation can alleviate pain behaviors in a rat model of trigeminal neuropathic pain. Transmission of trigeminal pain signals can be modulated via knock-down of α-CGRP and optical motor cortex stimulation.