Neuronavigated percutaneous gasserian radiofrequency thermorhizotomy for trigeminal neuralgia: how I do it.

BACKGROUND: Radiofrequency thermorhizotomy (TRZ) is an established treatment for trigeminal neuralgia (TN). TRZ can result risky and painful in a consistent subset of patients, due to the need to perform multiple trajectories, before a successful foramen ovale cannulation. Moreover, intraoperative x-rays are required. METHOD: TRZ has been performed by using a neuronavigated stylet, before trajectory planning on a dedicated workstation. CONCLUSION: Navigated-TRZ (N-TRZ) meets the expectations of a safer and more tolerable procedure due to the use of a single trajectory, avoiding critical structures. Moreover, N-TRZ is x-ray free. Efficacy outcomes are similar to those reported in literature.

Predicting balloon shape in percutaneous microcompression : an observational comparative analysis of Meckel's cave imaging and balloon morphology.

Achieving a pear-shaped balloon holds pivotal significance in the context of successful percutaneous microcompression procedures for trigeminal neuralgia. However, inflated balloons may assume various configurations, whether it is inserted into Meckel's cave or not. The absence of an objective evaluation metric has become apparent. To investigate the relationship between the morphology of Meckel's Cave and the balloon used in percutaneous microcompression for trigeminal neuralgia and establish objective criteria for assessing balloon shape in percutaneous microcompression procedures. This retrospective study included 58 consecutive patients with primary trigeminal neuralgia. Data included demographic, clinical outcomes, and morphological features of Meckel's cave and the balloon obtained from MRI and Dyna-CT imaging. MRI of Meckel's cave and Dyna-CT of intraoperative balloon were modeled, and the morphological characteristics and correlation were analyzed. The reconstructed balloon presented a fuller morphology expanding outward and upward on the basis of Meckel's cave. The projected area of balloon was strongly positively correlated with the projected area of Meckel's cave. The Pearson correlation coefficients were 0.812 (P<0.001) for axial view, 0.898 (P<0.001) for sagittal view and 0.813 (P<0.001) for coronal view. Similarity analysis showed that the sagittal projection image of Meckel's cave and that of the balloon had good similarity. This study reveals that the balloon in percutaneous microcompression essentially represents an expanded morphology of Meckel's cave, extending outward and upward. There is a strong positive correlation between the volume and projected area of the balloon and that of Meckel's cave. Notably, the sagittal projection image of Meckel's cave serves as a reliable predictor of the intraoperative balloon shape. This method has a certain generalizability and can help providing objective criteria for judging balloon shape during percutaneous microcompression procedures.

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.

Protocol for a systematic mapping review of surgical and pharmacological interventions for the treatment of trigeminal neuralgia.

Introduction: Trigeminal neuralgia is a painful neuropathic disorder characterized by sudden electric shock-like pain that significantly impacts patients' quality of life. Multiple treatment alternatives are available, including medical and surgical options but establishing the optimal course of action can be challenging. To enhance clinical decision-making for trigeminal neuralgia treatment, it is imperative to organize, describe and map the available systematic reviews and randomized trials. This will help identify the best treatment alternatives supported by evidence and acknowledge potential knowledge gaps where future research is needed. Objective: This systematic mapping review aims to provide up-to-date evidence on the different surgical and pharmacological treatment alternatives used for trigeminal neuralgia. Methods: A search will be systematically conducted on the Epistemonikos database to identify potentially eligible systematic reviews. Additionally, a search will be made in PubMed, CENTRAL, and EBSCO to identify randomized controlled trials assessing pharmacological and surgical treatment interventions for trigeminal neuralgia. Two independent reviewers will screen and select the studies. Data on the different treatment alternatives and reported outcomes in the included studies will be extracted using standardized forms. Following extraction, descriptive statistical methods will be used to analyze the data. The final output of this study will include an evidence map that will illustrate the connections between different treatments and their respective outcomes, providing a clear depiction of the evidence landscape. Expected results: This study expects to map, describe and assess the methodological quality of the available systematic reviews and trials on pharmacological interventions and neurosurgical procedures for treating trigeminal neuralgia. It will present the results in an evidence map that organizes the available evidence based on their different interventions and outcomes. This evidence map will serve as a visual tool to assist healthcare professionals and patients to understand evidence-based treatment options and their implications for managing this medical condition. Introducción: La neuralgia del trigémino es un trastorno neuropático doloroso caracterizado por un dolor súbito y agudo, similar a una descarga eléctrica, que impacta significativamente en la calidad de vida. Dada la variedad de tratamientos disponibles, médicos y quirúrgicos, es crucial organizar y mapear la evidencia proveniente de revisiones sistemáticas y ensayos clínicos para orientar las decisiones clínicas. Esto permite identificar tratamientos respaldados por evidencia y señalar áreas de investigación futura. Objetivo: El propósito de esta revisión sistemática de mapeo es proporcionar una visión actualizada de la evidencia existente en relación con las diversas opciones de tratamiento quirúrgico y farmacológico empleadas en el manejo de la neuralgia del trigémino. Métodos: Se realizará una búsqueda sistemática en la base de datos Epistemonikos para identificar potenciales revisiones sistemáticas. Adicionalmente, se buscará en PubMed, CENTRAL y EBSCO ensayos clínicos aleatorizados que evalúen intervenciones de tratamiento farmacológico y quirúrgico para la neuralgia del trigémino. Dos revisores independientes cribarán y seleccionarán los estudios. Se extraerán datos sobre las diferentes alternativas de tratamiento y los resultados reportados en los estudios incluidos utilizando formularios estandarizados. Tras la extracción, se utilizarán métodos estadísticos descriptivos para analizar los datos. El producto final de este estudio incluirá un mapa de evidencia que ilustrará las conexiones entre los diferentes tratamientos y sus respectivos resultados, proporcionando una representación clara del panorama de la evidencia. Resultados esperados: Los resultados que se extraerán de este mapeo sistemático incluyen identificar y describir las diferentes alternativas, tanto farmacológicas como quirúrgicas, que existen para el tratamiento de la neuralgia del trigémino. Además, se planea presentar un mapa de evidencia que se basará en los ensayos clínicos aleatorizados y revisiones sistemáticas, el cual mostrará la evidencia de manera organizada entre las diferentes intervenciones y sus desenlaces. Este mapa de evidencia servirá como una herramienta visual que ayudará a los profesionales de la salud y los pacientes a comprender mejor las opciones de tratamiento respaldadas por la evidencia y sus consecuencias en el manejo de esta condición médica.

Exploring the mechanism of Nav1.3 in the ION-CCI rat model based on the TLR4/TRAF6/NF-κB pathway.

BACKGROUND: Trigeminal neuralgia (TN) is a common and difficult-to-treat neuropathic pain disorder in clinical practice. Previous studies have shown that Toll-like receptor 4 (TLR4) modulates the activation of the NF-κB pathway to affect neuropathic pain in rats. Voltage-gated sodium channels (VGSCs) are known to play an important role in neuropathic pain electrical activity. OBJECTIVE: To investigate whether TLR4 can regulate Nav1.3 through the TRAF6/NF-κB p65 pathway after infraorbital nerve chronic constriction injury (ION-CCI). STUDY DESIGN: ION-CCI modeling was performed on SD (Sprague Dawley) rats. To verify the success of the modeling, we need to detect the mechanical pain threshold and ATF3. Then, detecting the expression of TLR4, TRAF6, NF-κB p65, p-p65, and Nav1.3 in rat TG. Subsequently, investigate the role of TLR4/TRAF6/NF-κB pathway in ION-CCI model by intrathecal injections of LPS-rs (TLR4 antagonist), C25-140 (TRAF6 inhibitor), and PDTC (NF-κB p65 inhibitor). RESULTS: ION-CCI surgery decreased the mechanical pain threshold of rats and increased the expression of ATF3, TLR4, TRAF6, NF-κB p-p65 and Nav1.3, but there was no difference in NF-κB p65 expression. After inject antagonist or inhibitor of the TLR4/TRAF6/NF-κB pathway, the expression of Nav1.3 was decreased and mechanical pain threshold was increased. CONCLUSION: In the rat model of ION-CCI, TLR4 in the rat trigeminal ganglion regulates Nav1.3 through the TRAF6/NF-κB p65 pathway, and TLR4 antagonist alleviates neuropathic pain in ION-CCI rats.

Effect of Carbamazepine on Darunavir Trough Concentrations: When the Dose Can Make the Difference-A Case Study.

BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations. METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia. RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses. CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.

Retrogasserian trigeminal radiofrequency-thermorhizotmoy for trigeminal neuralgia.

Based on a personal experience of 4200 surgeries, radiofrequency thermocoagulation is useful lesional treatment for those trigeminal neuralgias (TNs) not amenable to microvascular decompression (idiopathic or secondary TNs). Introduced through the foramen ovale, behind the trigemnial ganglion in the triangular plexus, the needle is navigated by radiology and neurophysiological testing to target the retrogasserian fibers corresponding to the trigger zone. Heating to 55-75 °C can achieve hypoesthesia without anaesthesia dolorosa if properly controlled. Depth of anaesthesia varies dynamically sedation for cannulation and lesioning, and awareness during neurophysiologic navigation. Proper technique ensures long-lasting results in more than 75% of patients.

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.

Trigeminal neuralgia.

Trigeminal neuralgia (TN) is a facial pain disorder characterized by intense and paroxysmal pain that profoundly affects quality of life and presents complex challenges in diagnosis and treatment. TN can be categorized as classical, secondary and idiopathic. Epidemiological studies show variable incidence rates and an increased prevalence in women and in the elderly, with familial cases suggesting genetic factors. The pathophysiology of TN is multifactorial and involves genetic predisposition, anatomical changes, and neurophysiological factors, leading to hyperexcitable neuronal states, central sensitization and widespread neural plasticity changes. Neurovascular compression of the trigeminal root, which undergoes major morphological changes, and focal demyelination of primary trigeminal afferents are key aetiological factors in TN. Structural and functional brain imaging studies in patients with TN demonstrated abnormalities in brain regions responsible for pain modulation and emotional processing of pain. Treatment of TN involves a multifaceted approach that considers patient-specific factors, including the type of TN, with initial pharmacotherapy followed by surgical options if necessary. First-line pharmacological treatments include carbamazepine and oxcarbazepine. Surgical interventions, including microvascular decompression and percutaneous neuroablative procedures, can be considered at an early stage if pharmacotherapy is not sufficient for pain control or has intolerable adverse effects or contraindications.

Intraoperative monitoring of trigeminal neuralgia: a technical note.

Trigeminal neuralgia causes excruciating pain in patients. Microvascular decompression is indicated for drug-resistant s trigeminal neuralgia. Unlike facial spasms, any part of the nerve can be the culprit, not only the root entry zone. Intraoperative monitoring does not yet exist for trigeminal neuralgia. We successfully used intermittent stimulation of the superior cerebellar artery during surgery and confirmed the disappearance of the trigeminal nerve motor branch reaction after the release of the compression. Intermittent direct stimulation of the culprit blood vessel using the motor branch of the trigeminal nerve may assist in intraoperative monitoring of decompression during trigeminal nerve vascular decompression surgery.

Efficacy and safety of microvascular decompression with or without partial sensory rhizotomy: a comprehensive meta-analysis and systematic review in treating trigeminal neuralgia.

Classical trigeminal neuralgia (TN), caused by vascular compression of the nerve root, is a severe cause of pain with a considerable impact on a patient's quality of life. While microvascular decompression (MVD) has lower recurrence rates when compared with partial sensory rhizotomy (PSR) alone, refractoriness can still be as high as 47%. We aimed to assess the efficacy and safety profile of MVD + PSR when compared to standalone MVD for TN. We searched Medline, Embase, and Web of Science following PRISMA guidelines. Eligible studies included those with ≥ 4 patients, in English, published between January 1980 and December 2023, comparing MVD vs. MVD + PSR for TN. Endpoints were pain cure, immediate post-operative pain improvement, long-term effectiveness, long-term recurrence, and complications (facial numbness, hearing loss, and intracranial bleeding). We pooled odds ratios (OR) with 95% confidence intervals with a random-effects model. I2 was used to assess heterogeneity, and sensitivity and Baujat analysis were conducted to address high heterogeneity. Eight studies were included, comprising a total of 1,338 patients, of whom 1,011 were treated with MVD and 327 with MVD + PSR. Pain cure analysis revealed a lower likelihood of pain cure in patients treated with MVD when compared to patients treated with MVD + PSR (OR = 0.30, 95% CI: 0.13 to 0.72). Immediate postoperative pain improvement assessment revealed a lower likelihood of improvement in the MVD group when compared with the MVD + PSR group (OR = 0.31, 95% CI: 0.10 to 0.95). Facial numbness assessment revealed a lower likelihood of occurrence in MVD alone when compared to MVD + PSR (OR = 0.08, 95% CI: 0.04 to 0.15). Long-term effectiveness, long-term recurrence, hearing loss, and intracranial bleeding analyses revealed no difference between both approaches. Our meta-analysis identified that MVD + PSR was superior to MVD for pain cure and immediate postoperative pain improvement for treating TN. However, MVD + PSR demonstrated a higher likelihood of facial numbness complications. Furthermore, identified that hearing loss and intracranial bleeding complications appear comparable between the two treatments, and no difference between long-term effectiveness and recurrence.

Letter to the editor: "A nomogram based on radiomics and clinical information to predict prognosis in percutaneous balloon compression for the treatment of trigeminal neuralgia: a retrospective cohort study of published cases".

This critique evaluates a recent study on a nomogram based on radiomics and clinical data to predict the prognosis of percutaneous balloon compression (PBC) for trigeminal neuralgia (TN), focusing on its strengths, weaknesses, and suggestions for future research. It acknowledges the innovative approach's potential to personalize treatment and improve outcomes, but raises concerns about the study's retrospective nature, sample size limitations, and challenges in implementing radiomics in clinical practice. Overall, although the nomogram offers promise, further validation in larger cohorts is essential to confirm its utility and reliability. Future research should prioritize prospective multicenter studies with standardized protocols, collaborative efforts among institutions, and innovative techniques to advance our understanding and management.

Compared to oxcarbazepine and carbamazepine, botulinum toxin type A is a useful therapeutic option for trigeminal neuralgia symptoms: A systematic review.

OBJECTIVES: This review aimed to compare the effectiveness of three treatments: BTX A, CBZ, and OXB, in managing trigeminal neuralgia (TN). MATERIAL AND METHODS: We conducted a thorough search for research articles related to our issue using specific keywords on several databases, including Cochrane Central Register of Controlled Trials, Science Direct, Scopus, PubMed, Elsevier, Springer Journals, Ovid Medline, EBSCO, and Web of Science. Our focus was on publications from 1965 to 2023. RESULTS: We retrieved 46 articles from the search and reviewed them carefully. Out of these, we selected 29 articles that met the inclusion criteria. Among the selected articles, 11 investigated the effects of CBZ and OXB, while 18 explored the impact of BTX A on the improvement of TN symptoms. The response rate ranged between 56% and 90.5% for CBZ and between 90.9% and 94% for OXB. The response rate for BTX A ranged between 51.4% and 100%. All these three treatments had a remarkable effect on the improvement of TN. Importantly, findings highlighted that side effects of CBZ and OXB could lead to treatment discontinuation in some cases, whereas BTX A's side effects have been minimal and less frequent. CONCLUSIONS: Consequently, BTX A emerges as a promising alternative for TN treatment. However, additional clinical trials are necessary to validate this finding, and further research is required to establish a standardized protocol for administering BTX A in TN.

Progress in study on animal models of trigeminal neuralgia. / ä¸‰å‰ç¥žç»ç—›åŠ¨ç‰©æ¨¡åž‹çš„ç ”ç©¶è¿›å±•.

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

Comparison of initial percutaneous balloon compression versus radiofrequency thermocoagulation followed by percutaneous balloon compression in the treatment of trigeminal neuralgia. / 首次经皮球囊压迫术与射频热凝术后再行经皮球囊压迫术治疗三叉神经痛的比较.

OBJECTIVES: There are a variety of minimally invasive interventional treatments for trigeminal neuralgia, and the efficacy evaluation is different. The preferred treatment scheme is still controversial. This study aims to investigate the differences in treatment effects between patients with primary trigeminal neuralgia (PTN) treated with percutaneous balloon compression (PBC) for the first intervention and patients with pain recurrence after radiofrequency thermocoagulation (RT) who then received PBC for PTN, and to offer clinicians and patients more scientifically grounded and precise treatment alternatives. METHODS: We retrospectively analyzed 103 patients with PTN admitted to the Department of Pain Management of the Second Affiliated Hospital of Guangxi Medical University from January 2020 to December 2021, including 49 patients who received PBC for the first time (PBC group) and 54 patients who received PBC for pain recurrence after RT (RT+PBC group). General information, preoperative pain score, intraoperative oval foramen morphology, oval foramen area, balloon volume, duration of compression, and postoperative pain scores and pain recurrence at each time point on day 1 (T1), day 7 (T2), day 14 (T3), 1 month (T4), 3 months (T5), and 1 year (T6) were collected and recorded for both groups. The differences in treatment effect, complications and recurrence between the 2 groups were compared, and the related influencing factors were analyzed. RESULTS: The differences of general information, preoperative pain scores, foramen ovale morphology, foramen ovale area, T1 to T3 pain scores between the 2 groups were not statistically different (all P>0.05). The balloon filling volume in the PBC group was smaller than that in the RT+PBC group, the pain scores at T4 to T6 and pain recurrence were better than those in the RT+PBC group (all P<0.05). Pain recurrence was positively correlated with pain scores of T2 to T6 (r=0.306, 0.482, 0.831, 0.876, 0.887, respectively; all P<0.01). CONCLUSIONS: The choice of PBC for the first intervention in PTN patients is superior to the choice of PBC after pain recurrence after RT treatment in terms of treatment outcome and pain recurrence.

Effects of carbamazepine on BDNF expression in trigeminal ganglia and serum in rats with trigeminal neuralgia. / å¡é©¬è¥¿å¹³å¯¹ä¸‰å‰ç¥žç»ç—›å¤§é¼ ä¸‰å‰ç¥žç»èŠ‚åŠè¡€æ¸ ä¸­BDNF表达变化的影响.

OBJECTIVES: Trigeminal neuralgia (TN) is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy. There are numerous treatments for TN, but currently the main clinical approach is to suppress pain by carbamazepine (CBZ). Brain-derived neurotrophic factor (BDNF) is closely related to chronic pain. This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion (TG) and serum of TN via a chronic constriction injury of the infraorbital nerve (ION-CCI) rat model. METHODS: The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group, a TN group, a TN+low-dose CBZ treatment group (TN+20 mg/kg CBZ group), a TN+medium-dose CBZ treatment group (TN+40 mg/kg CBZ group), and a TN+high-dose CBZ treatment group (TN+80 mg/kg CBZ group). The mechanical pain threshold in each group of rats was measured regularly before and after surgery. The expressions of BDNF and tyrosine kinase receptor B (TrkB) mRNA in TGs of rats in different groups were determined by real-time PCR, and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence. Western Blotting was used to detect the protein expression of BDNF, TrkB, extracellular regulated protein kinases (ERK), and phospho-extracellular regulated protein kinases (p-ERK) in TGs of rats in different groups. The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery (all P>0.05). From the 3rd day after operation, the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group (all P<0.01), and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 CBZ mg/kg group was higher than that in the TN group (all P<0.05). The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group (all P<0.05), and those in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than the TN group (all P<0.05). The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group (all P<0.05). The BDNF and neuron-specific nuclear protein (NeuN) were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group (all P<0.05). The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group (P<0.05). The levels of BDNF in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold (r=-0.650, P<0.01). CONCLUSIONS: CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats, reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway, so as to inhibit TN. The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

MiR-21-5p alleviates trigeminal neuralgia in rats through down-regulation of voltage-gated potassium channel Kv1.1. / MiR-21-5p通过下调电压门控钾离子通道Kv1.1è¡¨è¾¾å‡è½»å¤§é¼ ä¸‰å‰ç¥žç»ç—›.

OBJECTIVES: Trigeminal neuralgia (TN) is a common neuropathic pain. Voltage-gated potassium channel (Kv) has been confirmed to be involved in the occurrence and development of TN, but the specific mechanism is still unclear. MicroRNA may be involved in neuropathic pain by regulating the expression of Kv channels and neuronal excitability in trigeminal ganglion (TG). This study aims to explore the relationship between Kv1.1 and miR-21-5p in TG with a TN model, evaluate whether miR-21-5p has a regulatory effect on Kv1.1, and to provide a new target and experimental basis for the treatment of TN. METHODS: A total of 48 SD rats were randomly divided into 6 groups: 1) a sham group (n=12), the rats were only sutured at the surgical incision without nerve ligation; 2) a sham+agomir NC group (n=6), the sham rats were microinjected with agomir NC through stereotactic brain injection in the surgical side of TG; 3) a sham+miR-21-5p agomir group (n=6), the sham rats were microinjected with miR-21-5p agomir via stereotactic brain injection in the surgical side of TG; 4) a TN group (n=12), a TN rat model was constructed using the chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) method with chromium intestinal thread; 5) a TN+antagonist NC group (n=6), TN rats were microinjected with antagonist NC through stereotactic brain injection method in the surgical side of TG; 6) a TN+miR-21-5p antagonist group (n=6), TN rats were microinjected with miR-21-5p antagonist through stereotactic brain injection in the surgical side of TG. The change of mechanical pain threshold in rats of each group after surgery was detected. The expressions of Kv1.1 and miR-21-5p in the operative TG of rats were detected by Western blotting and real-time reverse transcription polymerase chain reaction. Dual luciferase reporter genes were used to determine whether there was a target relationship between Kv1.1 and miR-21-5p and whether miR-21-5p directly affected the 3'-UTR terminal of KCNA1. The effect of brain stereotaxic injection was evaluated by immunofluorescence assay, and then the analogue of miR-21-5p (agomir) and agomir NC were injected into the TG of rats in the sham group by brain stereotaxic apparatus to overexpress miR-21-5p. The miR-21-5p inhibitor (antagomir) and antagomir NC were injected into TG of rats in the TN group to inhibit the expression of miR-21-5p. The behavioral changes of rats before and after administration were observed, and the expression changes of miR-21-5p and Kv1.1 in TG of rats after intervention were detected. RESULTS: Compared with the baseline pain threshold, the facial mechanical pain threshold of rats in the TN group was significantly decreased from the 5th to 15th day after the surgery (P<0.05), and the facial mechanical pain threshold of rats in the sham group was stable at the normal level, which proved that the dIoN-CCI model was successfully constructed. Compared with the sham group, the expression of Kv1.1 mRNA and protein in TG of the TN group was down-regulated (both P<0.05), and the expression of miR-21-5p was up-regulated (P<0.05). The results of dual luciferase report showed that the luciferase activity of rno-miR-21-5p mimics and KCNA1 WT transfected with 6 nmol/L or 20 nmol/L were significantly decreased compared with those transfected with mimic NC and wild-type KCNA1 WT, respectively (P<0.001). Compared with low dose rno-miR-21-5p mimics (6 nmol/L) co-transfection group, the relative activity of luciferase in the high dose rno-miR-21-5p mimics (20 nmol/L) cotransfection group was significantly decreased (P<0.001). The results of immunofluorescence showed that drugs were accurately injected into TG through stereotaxic brain. After the expression of miR-21-5p in the TN group, the mechanical pain threshold and the expression of Kv1.1 mRNA and protein in TG were increased. After overexpression of miR-21-5p in the sham group, the mechanical pain threshold and the expression of Kv1.1 mRNA and protein in TG were decreased. CONCLUSIONS: Both Kv1.1 and miR-21-5p are involved in TN and miR-21-5p can regulate Kv1.1 expression by binding to the 3'-UTR of KCNA1.