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.

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.

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.

Amaurosis and transient diplopia, a rare complication secondary to mandibular nerve block: A case report.

Ocular complications are one of the rare side effects that can be seen after a mandibular nerve block and have the most dramatic results. Since the mandibular nerve block is mostly performed by dentists, this complication is mostly seen after an intraoral mandibular nerve block. The mandibular nerve is the third division of the trigeminal nerve. It is the most caudal and lateral part of Gasser's ganglion. It arises from the middle cranial fossa through the foramen ovale. In this region, a block method, which is performed by passing through the coronoid process, has been defined. This block, usually made using anatomical markers, is used in the treatment of trigeminal neuralgia. A 42-year-old female patient was admitted to our department for a maxillary and mandibular block with a diagnosis of trigeminal neuralgia. Immediately after the administration of the local anesthetic, the patient described a complete loss of vision. The complaint of vision loss lasted for about 1 minute, after which the patient's complaint of diplopia continued for 2 hours and 10 minutes. This case report presents the ocular complications after a mandibular block applied with the extraoral technique as an unexpected side effect.

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.

Botulinum toxin-A as a treatment option for refractory idiopathic trigeminal neuralgia of the ophthalmic branch: a case report and literature review.

Trigeminal neuralgia is one of the most common neurological pains affecting the head and neck and is associated with severe, lancinating, electrical pain episodes. The maxillary and mandibular branches are usually affected. The ophthalmic branch is rarely involved and, when present, it requires a comprehensive workup to rule out major conditions. Pharmacotherapy and surgery are the most common treatment options for this condition. Systemic medications may pose a wide range of side effects and effectiveness may decrease over time while surgery has inherent complications. Injectable onabotulinum toxins have been utilized for various applications in medicine and dentistry. There is, however, limited data on their use for the management of refractory trigeminal neuralgia of the ophthalmic branch. We present the case of a 58-year-old male diagnosed with refractory idiopathic trigeminal neuralgia affecting the ophthalmic branch, which was unresponsive to standard care and successfully managed with onabotulinum toxin type A. This treatment should be considered in cases of refractory trigeminal neuralgia prior to surgery. We reviewed the relevant literature concerning the application of Onabotulinum toxin A for managing trigeminal neuralgia of the ophthalmic branch. This case report and review aim to enlighten the application of Onabotulinum toxin A for managing refractory trigeminal neuralgia of the ophthalmic branch. Our case report and review show that Onabotulinum toxin A could be used for managing TN of the ophthalmic branch.

Clinical Efficacy of Percutaneous Balloon Compression Combined with Carbamazepine in the Treatment of Trigeminal Neuralgia: A Retrospective Study.

OBJECTIVE: To investigate the effect of percutaneous balloon compression combined with carbamazepine on patients with Trigeminal Neuralgia (TN). METHODS: The clinical data of 126 patients with TN admitted to our hospital from January, 2021 to January, 2022 were retrospectively analyzed. All patients underwent percutaneous balloon compression in our hospital. The patients were divided into a control group and an observation group, according to whether they continued to take carbamazepine after surgery. The general demographic data of patients, such as gender, age, family income, education level, pain site, diseased nerve, course of disease, and duration of pain were collected. Propensity score matching was used to balance the baseline data of the two groups, and the quality of life, treatment effect, and complications of the two groups were compared after matching. RESULTS: After treatment, the total effective rate of the observation group (95.00%) was higher than that of the control group (70.00%) (p < 0.05). Before treatment, there were no significant differences in the scores for quality of life dimensions between the two groups (p > 0.05). After treatment, the scores for each quality of life dimension in the observation group were higher than those in the control group. After treatment, the incidence of complications in the observation group (7.50%) was lower than that in the control group (30.00%) (p < 0.05). CONCLUSIONS: Percutaneous balloon compression combined with carbamazepine can effectively enhance the treatment of patients by improving their quality of life and reducing the occurrence of complications. These results can improve the clinical management of TN.

Efficacy and Safety of Computed Tomography-Guided Percutaneous Balloon Compression under Local Anesthesia for Recurrent Trigeminal Neuralgia: A Prospective Study.

Purpose: There are several ways to treat trigeminal neuralgia (TN); however, TN may recur after treatment. This study investigated the efficacy and safety of computed tomography (CT)-guided percutaneous balloon compression (PBC) under local anesthesia for treatment of recurrent trigeminal neuralgia. Patients and Methods. This is a prospective and nonrandomized controlled clinical study. Forty-eight patients with classical TN were scheduled to undergo PBC surgery at the pain department of our institution between January 2021 and June 2021. The patients were prospectively divided into an initial onset group, A (21 cases), and a recurrence group, B (27 cases). All surgeries were performed with CT guidance and under local anesthesia. Postoperative complications were also observed. Pain was assessed using the visual analog scale (VAS) and Barrow Neurological Institute (BNI) scale. Efficacy indices were evaluated at 3, 6, 12, and 18 months after surgery. Results: All participants reported complete pain relief at discharge. After 18 months of follow-up, the total effective rate of pain control was 89.5% (group A, 90.5%; group B, 88.8%). There was no significant difference in the BNI scores between the two groups before and after treatment. All patients had hypoesthesia on the affected side, and no severe complications such as diplopia, blindness, intracranial hemorrhage, or intracranial infection occurred. Conclusions: CT-guided PBC under local anesthesia is safe and effective for the treatment of recurrent TN and thus acts as an effective alternative for geriatric patients and those with high-risk factors.

Cannabidiol and it fluorinate analog PECS-101 reduces hyperalgesia and allodynia in trigeminal neuralgia via TRPV1 receptors.

Trigeminal neuralgia (TN) is an intense and debilitating orofacial pain. The gold standard treatment for TN is carbamazepine. This antiepileptic drug provides pain relief with limited efficacy and side effects. To study the antinociceptive potential of cannabidiol (CBD) and its fluorinated analog PECS-101 (former HUF-101), we induced unilateral chronic constriction injury of the infraorbital nerve (IoN-CCI) in male Wistar rats. Seven days of treatment with CBD (30 mg/kg), PECS-101 (3, 10, and 30 mg/kg), or carbamazepine (10 and 30 mg/kg) reduced allodynia and hyperalgesia responses. Unlike carbamazepine, CBD and PECS-101 did not impair motor activity. The relief of the hypersensitive reactions has been associated with transient receptor potential vanilloid type 1 (TRPV1) modulation in the trigeminal spinal nucleus. CBD (30 mg/kg) and PECS-101 (10 and 30 mg/kg) reversed the increased expression of TRPV1 induced by IoN-CCI in this nucleus. Using a pharmacological strategy, the combination of the selective TRPV1 antagonist (capsazepine-CPZ - 5 mg/kg) with sub-effective doses of CBD (3 and 10 mg/kg) is also able to reverse the IoN-CCI-induced allodynia and hyperalgesia responses. This effect was accompanied by reduced TRPV1 protein expression in the trigeminal spinal nucleus. Our results suggest that CBD and PECS-101 may benefit trigeminal neuralgia without motor coordination impairments. PECS-101 is more potent against the hypernociceptive and motor impairment induced by TN compared to CBD and carbamazepine. The antinociceptive effect of these cannabinoids is partially mediated by TRPV1 receptors in the caudal part of the trigeminal spinal nucleus, the first central station of orofacial pain processing.

Trigeminal neuralgia and trigeminal neuropathic pain.

It is very important that the dental team are aware of the varied presentations of pain in the mouth, face and other parts of the trigeminal region which are not directly caused by teeth or oral structures. Our understanding of underlying causes in this complex area is evolving. Ultimately, patients who present with what may at first seem to be oral or dental problems will require specialist input in secondary care with potential for use of systemic medications. This article reviews the common non-dental pains encountered in the orofacial region related to dysfunction of the trigeminal nerve.

Pharmacological and Non-pharmacological Approaches for the Management of Neuropathic Pain in Multiple Sclerosis.

Multiple sclerosis is a chronic inflammatory disease that affects the central nervous system and can cause various types of pain including ongoing extremity pain, Lhermitte's phenomenon, trigeminal neuralgia, and mixed pain. Neuropathic pain is a major concern for individuals with multiple sclerosis as it is directly linked to myelin damage in the central nervous system and the management of neuropathic pain in multiple sclerosis is challenging as the options available have limited efficacy and can cause unpleasant side effects. The literature search was conducted across two databases, PubMed, and Google Scholar. Eligible studies included clinical trials, observational studies, meta-analyses, systematic reviews, and narrative reviews. The objective of this article is to provide an overview of literature on pharmacological and non-pharmacological strategies employed in the management of neuropathic pain in multiple sclerosis. Pharmacological options include cannabinoids, muscle relaxants (tizanidine, baclofen, dantrolene), anticonvulsants (benzodiazepines, gabapentin, phenytoin, carbamazepine, lamotrigine), antidepressants (duloxetine, venlafaxine, tricyclic antidepressants), opioids (naltrexone), and botulinum toxin variants, which have evidence from various clinical trials. Non-pharmacological approaches for trigeminal neuralgia may include neurosurgical methods. Non-invasive methods, physical therapy, and psychotherapy (cognitive behavioral therapy, acceptance and commitment therapy and mindfulness-based stress reduction) may be recommended for patients with neuropathic pain in multiple sclerosis. The choice of treatment depends on the severity and type of pain as well as other factors, such as patient preferences and comorbidities. There is a pressing need for healthcare professionals and researchers to prioritize the development of better strategies for managing multiple sclerosis-induced neuropathic pain.

Sex differences in carbamazepine effects in a rat model of trigeminal neuropathic pain.

Carbamazepine (CBZ) represents the first-line treatment for trigeminal neuralgia, a condition of facial pain that affects mainly women. The chronic constriction of the infraorbital nerve (CCI-ION) is a widely used model to study this condition, but most studies do not include females. Thus, this study aimed to characterize sensory and affective changes in female rats after CCI-ION and compare the effect of CBZ in both sexes. Mechanical allodynia was assessed 15 days after CCI-ION surgery in rats treated with CBZ (10 and 30 mg/kg, i.p.) or vehicle, together with the open-field test. Independent groups were tested on the Conditioned Place Preference (CPP) paradigm and ultrasonic vocalization (USV) analysis. Blood samples were collected for dosage of the main CBZ metabolite. CBZ at 30 mg/kg impaired locomotion of CCI-ION male and sham and CCI-ION female rats and resulted in significantly higher plasma concentrations of 10-11-EPX-CBZ in the latter. Only male CCI-ION rats showed increased facial grooming which was significantly reduced by CBZ at 10 mg/kg. CBZ at 10 mg/kg significantly reduced mechanical allodynia and induced CPP only in female CCI-ION rats. Also, female CCI-ION showed reduced emission of appetitive USV but did not show anxiety-like behavior. In conclusion, male and female CCI-ION rats presented differences in the expression of the affective-motivational pain component and CBZ was more effective in females than males. Further studies using both sexes in trigeminal neuropathic pain models are warranted for a better understanding of potential differences in the pathophysiological mechanisms and efficacy of pharmacological treatments.

Efficacy and Safety of Botulinum Toxin Type A in the Treatment of Trigeminal Neuralgia: An Update on Systematic Review With Meta-analyses.

OBJECTIVE: Pain management in patients with TN is challenging, as facial pain often does not respond well to conventional therapies. Botulinum toxin type A (BTX-A) has been suggested as a potential treatment option, but there is limited evidence regarding its long-term efficacy. This review aimed to analyze the current data for the use of in the treatment of trigeminal neuralgia (TN) and highlight the evidence for its efficacy and safety. METHODS: A comprehensive search was conducted in various databases (PubMed, Scopus, Embase, ClinicalTrials, and Cochrane Library) to identify clinical studies evaluating the use of BTX-A in TN until October 2023. Randomized controlled trials (RCTs), single-arm studies, and stratified studies were included in the analysis. The mean difference (MD), effect size (ES), and 95% confidence interval (CI) were estimated for visual analogue scale (VAS) scores, pain episode frequency, and the proportion of responders. RESULTS: The analysis included 23 studies, including 4 RCTs, 14 single-arm studies, and 5 stratified studies. In the RCTs, BTX-A was found to significantly reduce mean VAS scores compared with baseline (ES: -4.05; 95% CI: -6.13, -1.97; P =0.002). In 19 non-RCTs, the pooled single-arm analysis revealed that BTX-A decreased VAS scores (ES: -5.19, 95% CI: -6.05, -4.33, P <0.001) and pain attack frequency (ES: -17.85, 95% CI: -23.36, -12.34, P <0.001) from baseline to the end of follow-up. The overall proportion of responders to BTX-A treatment was also significant (95% CI: 0.653, 0.761, P =0.003). DISCUSSION: Current evidence indicates that BTX-A injection is an effective and safe option for patients with refractory TN or not responding to medical or surgical management. However, more high-quality studies are needed to further confirm its efficacy.

[Pharmacological Treatment of Trigeminal Neuralgia].

Although carbamazepine is the first-line treatment option for trigeminal neuralgia, it may not be sustained long-term. The benefits of carbamazepine are offset by adverse effects that lead to its withdrawal. The alternatives to carbamazepine include gabapentin, pregabalin, and microgabalin. Although used off-label in Japan, baclofen, lamotrigine, intravenous lidocaine, and botulinum toxin type A are also effective. Clinical experience has shown that alternative treatments are less effective than carbamazepine. Therefore, they can be used instead of or in addition to carbamazepine. The adverse effects of drugs include drowsiness, dizziness, rash, bone marrow suppression, and liver dysfunction. Carbamazepine and lamotrigine are particularly likely to cause severe drug eruptions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Low-dose titration is important to avoid the development of rashes and adverse effects.

Intranasal CRMP2-Ubc9 inhibitor regulates Na V 1.7 to alleviate trigeminal neuropathic pain.

ABSTRACT: Dysregulation of voltage-gated sodium Na V 1.7 channels in sensory neurons contributes to chronic pain conditions, including trigeminal neuropathic pain. We previously reported that chronic pain results in part from increased SUMOylation of collapsin response mediator protein 2 (CRMP2), leading to an increased CRMP2/Na V 1.7 interaction and increased functional activity of Na V 1.7. Targeting this feed-forward regulation, we developed compound 194 , which inhibits CRMP2 SUMOylation mediated by the SUMO-conjugating enzyme Ubc9. We further demonstrated that 194 effectively reduces the functional activity of Na V 1.7 channels in dorsal root ganglia neurons and alleviated inflammatory and neuropathic pain. Here, we used a comprehensive array of approaches, encompassing biochemical, pharmacological, genetic, electrophysiological, and behavioral analyses, to assess the functional implications of Na V 1.7 regulation by CRMP2 in trigeminal ganglia (TG) neurons. We confirmed the expression of Scn9a , Dpysl2 , and UBE2I within TG neurons. Furthermore, we found an interaction between CRMP2 and Na V 1.7, with CRMP2 being SUMOylated in these sensory ganglia. Disrupting CRMP2 SUMOylation with compound 194 uncoupled the CRMP2/Na V 1.7 interaction, impeded Na V 1.7 diffusion on the plasma membrane, and subsequently diminished Na V 1.7 activity. Compound 194 also led to a reduction in TG neuron excitability. Finally, when intranasally administered to rats with chronic constriction injury of the infraorbital nerve, 194 significantly decreased nociceptive behaviors. Collectively, our findings underscore the critical role of CRMP2 in regulating Na V 1.7 within TG neurons, emphasizing the importance of this indirect modulation in trigeminal neuropathic pain.

Tapentadol helps in trigeminal neuralgia: a case report.

BACKGROUND: Trigeminal neuralgia (TN) usually affects people over 50 years old. TN-related pains are short-lived, and the disease course is characterized by exacerbations and remissions. Sometimes chronic pain develops due to central sensitization. This is the first case report on the effectiveness of tapentadol in pain control in TN. CASE DESCRIPTION: It is an instructive case history demonstrating the high effectiveness of tapentadol in a 55-year-old Caucasian male with severe [Visual Analogue Scale (VAS) 9/10] TN-related pain and a history of ineffective treatment with antiepileptic drugs. The neuralgia had occurred twice a year for the three preceding years, and typically the TN periods lasted 2-3 weeks with complete remissions between. Previously the patient had been treated with antiepileptic drugs (e.g., carbamazepine, phenytoin, clonazepam, gabapentin, and lamotrigine). However, he found all treatments to be ineffective and accompanied by unacceptable somnolence. Thus, a prolonged-release oral tapentadol was proposed at the beginning of the next relapse. After application of tapentadol, the patient reported a significant improvement. The severity of pain declined to VAS 6/10 (2nd day) and 4/10 (3rd day), and the attacks resolved entirely on the fourth day of treatment. He reported no side effects. The drug was discontinued after 14 days. CONCLUSIONS: Despite pain chronification, tapentadol was efficient and well tolerated in TN. Further research is needed to reveal tapentadol's efficacy in neuralgias.

Transplantation of olfactory ensheathing cells can alleviate neuroinflammatory responses in rats with trigeminal neuralgia.

Trigeminal neuralgia (TN) is a common form of facial pain, which primarily manifests as severe pain similar to facial acupuncture and electric shock. Olfactory ensheathing cells (OECs) are glial cells with high bioactivity; these cells are essential for the periodic regeneration of the olfactory nerve and have been utilized for the repair of nerve injuries. A member of the P2X receptor family, P2X7R, is an ion channel type receptor that has been confirmed to participate in various pain response processes. In this study, we transplanted OECs into trigeminal nerve-model rats with distal infraorbital nerve ligation to observe the therapeutic effect of transplanted OECs in rats. Additionally, we utilized the P2X7R-specific inhibitor brilliant blue G (BBG) to study the therapeutic mechanisms of cell transplantation. The facial mechanical pain threshold of these rats significantly increased following cell transplantation. The immunohistochemistry, immunoblotting, and RT-qPCR results demonstrated that the levels of P2X7R, (NOD)-like receptor protein-3 (NLRP3), nuclear factor-κB (NF-κB), interleukin (IL)-1ß, and IL-18 in the trigeminal ganglion of rats treated with OEC transplantation or BBG treatment were significantly lower than those in the injured group without treatment. Overall, our results demonstrate that OEC transplantation can alleviate TN in rats, and it can reduce the expression of P2X7R related inflammatory factors in TN rats, reducing neuroinflammatory response in TG.

The Therapeutic Effect of Botulinum Toxin Type A on Trigeminal Neuralgia: Are There Any Differences between Type 1 versus Type 2 Trigeminal Neuralgia?

BACKGROUND: Botulinum toxin type A is an effective treatment for trigeminal neuralgia. Moreover, its efficacy in type 2 trigeminal neuralgia and comparative studies between type 1 and type 2 trigeminal neuralgia (TN) still need to be improved. METHODS: We treated 40 TN patients with onabotulinumtoxinA; 18 had type 1 TN, and 22 had type 2 TN. We compared the baseline pain score with the Visual Analogue Scale (VAS) and paroxysm frequency (number per week) at the baseline with those obtained at 1-month and 3-month follow-ups. Nonetheless, we compared the baseline Penn Facial Pain Scale with the scores obtained at the 1-month follow-up. RESULTS: BoNT/A effectively reduced pain intensity and frequency at the 1-month and 3-month follow-ups. Moreover, the type 1 TN and type 2 TN groups had baseline pain scores of 7.8 ± 1.65 and 8.4 ± 1.1, respectively. Pain significantly improved (p < 0.001) in both groups to 3.1 ± 2.3 (type 1 TN) and 3.5 ± 2.3 (type 2 TN) at the 1-month follow-up and to 3.2 ± 2.5 (type 1 TN) and 3.6 ± 2.5 (type 2 TN) at the 3-month follow-up. There was no difference between the two groups (p 0.345). The baseline paroxysm frequencies (number per week) were 86.7 ± 69.3 and 88.9 ± 62.2 for the type 1 and type 2 TN groups, respectively; they were significantly reduced in both groups at the 1-month and 3-month follow-ups without significant differences between the two groups (p 0.902). The Pain Facial Pain Scale improved at the 1-month follow-up, and no significant differences were found between the two groups. There was a strong correlation between background pain and paroxysm pain intensity (r 0.8, p < 0.001). CONCLUSIONS: Botulinum toxin type A effectively reduced the pain, paroxysm frequency, and PFPS scores of type 1 and type 2 trigeminal neuralgia patients without statistically significant differences. Facial asymmetry was the only adverse event.

BMP7 alleviates trigeminal neuralgia by reducing oligodendrocyte apoptosis and demyelination.

BACKGROUND: BMP7 has been shown to have neuroprotective effects and to alleviate demyelination. However, its role in trigeminal neuralgia (TN) has not been well investigated. The current study aims to determine whether BMP7 plays a role in demyelination, its effects on pain behaviors and mechanism of action in rats with TN. METHODS: We used an infraorbital-nerve chronic-constriction injury (ION-CCI) to establish a rat model of TN. Adeno-associated viruses (AAVs) were injected into the rats to upregulate or downregulate BMP7. The mechanical withdrawal thresholds (MWT) of the injured rats were detected using Von Frey filaments. The changes in expression levels of BMP7 and oligodendrocyte (OL) markers were examined by western blotting, quantitative real-time PCR, immunofluorescence, and transmission electron microscopy. RESULTS: The ION-CCI induced mechanical allodynia, demyelination, and loss of OLs with a reduction of BMP7. Short-hairpin RNA (shRNA)-BMP7 that inhibited BMP7 expression also caused mechanical allodynia, demyelination, and loss of OLs, and its mechanism may be OL apoptosis. Overexpressing BMP7 in the trigeminal spinal subnucleus caudalis(VC) with AAV-BMP7 relieved all three phenotypes induced by the CCI, and its mechanism may be alleviating OLs apoptosis. Two signal pathways associated with apoptosis, STAT3 and p65, were significantly downregulated in the VC after CCI and rescued by BMP7 overexpression. CONCLUSION: BMP7 can alleviate TN by reducing OLs apoptosis and subsequent demyelination. The mechanism behind this protection could be BMP7-mediated activation of the STAT3 and NF-κB/p65 signaling pathway and subsequent decrease in OL apoptosis. Importantly, our study presents clear evidence in support of BMP7 as a possible therapeutic target for the treatment of TN.

GFAP-NpHR mediated optogenetic inhibition of trigeminal nucleus caudalis attenuates hypersensitive behaviors and thalamic discharge attributed to infraorbital nerve constriction injury.

The significance of hyperactive astrocytes in neuropathic pain is crucial. However, the association between medullary astrocytes and trigeminal neuralgia (TN)-related pain processing is unclear. Here, we examined how optogenetic inhibition of medullary astrocytes in the trigeminal nucleus caudalis (TNC) regulates pain hypersensitivity in an infraorbital nerve (ION) constricted TN model. We used adult Sprague Dawley rats subjected to infraorbital nerve (ION) constriction to mimic TN symptoms, with naive and sham rats serving as controls. For in vivo optogenetic manipulations, rats stereotaxically received AAV8-GFAP-eNpHR3.0-mCherry or AAV8-GFAP-mCherry at the trigeminal nucleus caudalis (TNC). Open field, von Frey, air puff, and acetone tests measured pain behavioral flexibility. In vivo thalamic recordings were obtained simultaneously with optogenetic manipulation in the TNC. Orofacial hyperalgesia and thalamic hyperexcitability were both accompanied by medullary astrocyte hyperactivity, marked by upregulated GFAP. The yellow laser-driven inhibition of TNC astrocytes markedly improved behavioral responses and regulated thalamic neuronal responses. Halorhodopsin-mediated inhibition in medullary astrocytes may modify the nociceptive input transmitted through the trigeminothalamic tract and pain perception. Taken together, these findings imply that this subpopulation in the TNC and its thalamic connections play a significant role in regulating the trigeminal pain circuitry, which might aid in the identification of new therapeutic measures in TN management.