RESUMEN
Sexual dimorphism among mammals includes variations in the pain threshold. These differences are influenced by hormonal fluctuations in females during the estrous and menstrual cycles of rodents and humans, respectively. These physiological conditions display various phases, including proestrus and diestrus in rodents and follicular and luteal phases in humans, distinctly characterized by varying estrogen levels. In this study, we evaluated the capsaicin responses in male and female mice at different estrous cycle phases, using two murine acute pain models. Our findings indicate that the capsaicin-induced pain threshold was lower in the proestrus phase than in the other three phases in both pain assays. We also found that male mice exhibited a higher pain threshold than females in the proestrus phase, although it was similar to females in the other cycle phases. We also assessed the mRNA and protein levels of TRPV1 in the dorsal root and trigeminal ganglia of mice. Our results showed higher TRPV1 protein levels during proestrus compared to diestrus and male mice. Unexpectedly, we observed that the diestrus phase was associated with higher TRPV1 mRNA levels than those in both proestrus and male mice. These results underscore the hormonal influence on TRPV1 expression regulation and highlight the role of sex steroids in capsaicin-induced pain.
Asunto(s)
Capsaicina , Dolor , Canales Catiónicos TRPV , Animales , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Capsaicina/farmacología , Masculino , Femenino , Ratones , Dolor/metabolismo , Dolor/genética , Hormonas Esteroides Gonadales/metabolismo , Ciclo Estral/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Ganglio del Trigémino/metabolismo , Ganglio del Trigémino/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Caracteres Sexuales , ARN Mensajero/metabolismo , ARN Mensajero/genéticaRESUMEN
While interactions between neural crest and placode cells are critical for the proper formation of the trigeminal ganglion, the mechanisms underlying this process remain largely uncharacterized. Here, by using chick embryos, we show that the microRNA (miR)-203, whose epigenetic repression is required for neural crest migration, is reactivated in coalescing and condensing trigeminal ganglion cells. Overexpression of miR-203 induces ectopic coalescence of neural crest cells and increases ganglion size. By employing cell-specific electroporations for either miR-203 sponging or genomic editing using CRISPR/Cas9, we elucidated that neural crest cells serve as the source, while placode cells serve as the site of action for miR-203 in trigeminal ganglion condensation. Demonstrating intercellular communication, overexpression of miR-203 in the neural crest in vitro or in vivo represses an miR-responsive sensor in placode cells. Moreover, neural crest-secreted extracellular vesicles (EVs), visualized using pHluorin-CD63 vector, become incorporated into the cytoplasm of placode cells. Finally, RT-PCR analysis shows that small EVs isolated from condensing trigeminal ganglia are selectively loaded with miR-203. Together, our findings reveal a critical role in vivo for neural crest-placode communication mediated by sEVs and their selective microRNA cargo for proper trigeminal ganglion formation.
Asunto(s)
Comunicación Celular , Vesículas Extracelulares , MicroARNs , Cresta Neural , Ganglio del Trigémino , Cresta Neural/metabolismo , Cresta Neural/embriología , Cresta Neural/citología , Animales , MicroARNs/metabolismo , MicroARNs/genética , Ganglio del Trigémino/metabolismo , Ganglio del Trigémino/embriología , Ganglio del Trigémino/citología , Vesículas Extracelulares/metabolismo , Embrión de Pollo , Comunicación Celular/genética , Movimiento Celular/genética , Regulación del Desarrollo de la Expresión GénicaRESUMEN
BACKGROUND AND OBJECTIVE: Painful trigeminal neuropathy is a complex clinical entity due to its severity and refractoriness to pharmacological and interventional management. We describe our experience in treating refractory painful trigeminal neuropathy (RPTN) with gasserian ganglion stimulation (GGS). MATERIALS AND METHODS: Six patients with RPTN were treated with GGS in our Unit between 2019 and 2022. The following data were collected: socio-demographic characteristics, triggering event, duration of the disease and treatment received prior to surgery, pre- and post-intervention visual analogue scale (VAS) score, follow-up time, and pre- and post-intervention functionality and quality of life. RESULTS: All patients were women who had received aggressive first-, second-, and third-line pharmacological, non-pharmacological, and interventional management before being referred for GGS. Patients reported a 50%-72% decrease in pain on VAS and improved functionality during follow-up. CONCLUSIONS: GGS is a promising therapeutic alternative for patients with RPTN. Although the initial outcomes and experience are encouraging, RPTN is recommended on the basis of safety, reproducibility, and trends observed in clinical practice.
Asunto(s)
Terapia por Estimulación Eléctrica , Ganglio del Trigémino , Neuralgia del Trigémino , Humanos , Femenino , Neuralgia del Trigémino/terapia , Persona de Mediana Edad , Terapia por Estimulación Eléctrica/métodos , Anciano , Dimensión del Dolor/métodos , Adulto , Resultado del TratamientoRESUMEN
Herpes simplex virus 1 (HSV-1) or simplexvirus humanalpha 1 is a neurotropic virus that is responsible for orofacial infections in humans. More than 70% of the world's population may have seropositivity for HSV-1, and this virus is a leading cause of sporadic lethal encephalitis in humans. The role of toll-like receptors (TLRs) in defending against HSV-1 infection has been explored, including the consequences of lacking these receptors or other proteins in the TLR pathway. Cell and mouse models have been used to study the importance of these receptors in combating HSV-1, how they relate to the innate immune response, and how they participate in the orchestration of the adaptive immune response. Myeloid differentiation factor 88 (MyD88) is a protein involved in the downstream activation of TLRs and plays a crucial role in this signaling. Mice with functional MyD88 or TLR2 and TLR9 can survive HSV-1 infection. However, they can develop encephalitis and face a 100% mortality rate in a dose-dependent manner when MyD88 or TLR2 plus TLR9 proteins are non-functional. In TLR2/9 knockout mice, an increase in chemokines and decreases in nitric oxide (NO), interferon (IFN) gamma, and interleukin 1 (IL-1) levels in the trigeminal ganglia (TG) have been correlated with mortality.
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Encefalitis , Herpes Simple , Herpesvirus Humano 1 , Humanos , Animales , Ratones , Herpesvirus Humano 1/metabolismo , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Ganglio del Trigémino/metabolismo , Receptores Toll-Like/metabolismo , Ratones Noqueados , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Trigeminal neuralgia is considered the worst pain a human being can experience. Initial treatment uses anticonvulsant sodium channel blockers, which relieve pain in approximately 70% of patients. In refractory cases, it is possible to perform ablative treatments, decompressive surgeries, and neuromodulatory techniques. METHODS: This report describes the treatment of a patient with refractory trigeminal neuralgia who continued to have a painful clinical presentation after four surgical procedures and three ablative procedures. The patient presented with severe pain (verbal numerical scale between 9 and 10), manifesting an evident suicidal ideation. A dorsal root ganglion (DRG) stimulation electrode was implanted in the trigeminal ganglion through intraoral puncture with maxillary fixation of the electrode, in order to minimize the chances of displacement. The test phase consisted of implanting a quadripolar electrode for DRG stimulation through puncture lateral to the buccal rim in a fluoroscopic coaxial view. The electrode was fixed to the skin and maintained for 5 days, during which the patient remained completely pain free. After the 5-day test period, the definitive stimulation electrode was implanted, this time with intraoral puncture and maxillary electrode fixation. RESULTS: The patient remains pain free in the 3-month follow-up, with no displacement of the electrode. CONCLUSIONS: The DRG electrode may be considered a therapeutic option in patients with severe trigeminal neuralgia. Controlled studies must be performed to determine the efficacy and safety of the method.
Asunto(s)
Terapia por Estimulación Eléctrica , Neuralgia del Trigémino , Humanos , Ganglios Espinales , Dolor , Terapia por Estimulación Eléctrica/métodos , Ganglio del Trigémino/cirugía , Electrodos Implantados , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the effect of a selective cyclooxygenase 2 (COX-2) inhibitor on trigeminal ganglion changes and orofacial discomfort/nociception in rats submitted to an experimental model of dental occlusal interference (DOI). METHODS: Female Wistar rats (180-200 g) were divided into five groups: a sham group (without DOI) (n=15); and four experimental groups with DOI treated daily with 0.1 mL/kg saline (DOI+SAL), 8, 16, or 32 mg/kg celecoxib (DOI+cel -8, -16, -32) (n=30/group). The animals were euthanized after one, three, and seven days. The bilateral trigeminal ganglia were analyzed histomorphometrically (neuron cell body area) and immunohistochemically (COX-2, nuclear factor-kappa B [NFkB], and peroxisome proliferator-activated receptor-y [PPARy]). A bilateral nociception assay of the masseter muscle was performed. The number of bites/scratches, weight, and grimace scale scores were determined daily. One-way/two-way analysis of variance (ANOVA)/Bonferroni post hoc tests were used (P < .05, GraphPad Prism 5.0). RESULTS: DOI+SAL showed a reduction in neuron cell body area bilaterally, whereas DOI+cel-32 exhibited a significative increase in neuron cell body area compared with DOI+SAL group (P < 0.05). The ipsilateral (P=0.007 and P=0.039) and contralateral (P < 0.001 and P=0.005) overexpression of COX-2 and NFkB and downregulation of PPARy (P=0.016 and P < 0.001) occurred in DOI+SAL, but DOI+cel-32 reverted this alteration. DOI+SAL showed increase in isplateral (P < 0.001) and contralateral (P < 0.001) nociception, an increased number of bites (P=0.010), scratches (P < 0.001), and grimace scores (P=0.032). In the group of DOI+cel-32, these parameters were reduced. CONCLUSIONS: Celecoxib attenuated DOI-induced transitory nociception/orofacial discomfort resulting from trigeminal COX-2 overexpression.
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Dolor Facial , Ganglio del Trigémino , Animales , Antiinflamatorios no Esteroideos/farmacología , Celecoxib/farmacología , Celecoxib/uso terapéutico , Ciclooxigenasa 2/farmacología , Oclusión Dental , Modelos Animales de Enfermedad , Dolor Facial/tratamiento farmacológico , Femenino , Ratas , Ratas WistarRESUMEN
Type III interferons (IFNs) are components of the innate immunity, with IFN lambda- (λ)3 having the most potent bioactivity in humans. IFN-λ has a predominant role in epithelial cells. However, antiviral function in certain infections of the central nervous system has also been demonstrated. IFN-λ3 expression in neural tissues of cattle has not been investigated. Thus, the aim of this study was to analyze whether an antiviral IFN-λ3 response is mounted after infection with bovine alphaherpesviruses (BoHV-1 and BoHV-5) in vitro, in neuronal-type cells, and in neural tissues from experimentally-infected calves. This study demonstrated that there is a strong IFN-λ3 response early after BoHV-1infection of undifferentiated neuroblastoma cells. During acute BoHV-1 and BoHV-5 infection of calves, low levels of IFN-λ3 expression were detected in the brain, which would favor virus spread within this tissue. Striking differences in the transcriptional levels of IFN-λ3 were observed in trigeminal ganglion, particularly in BoHV-1-acutely- and latently-infected calves. During reactivation, IFN-λ3 expression was down-regulated, which may be a requirement for virus replication and spread. Overall, different patterns of IFN-λ3 expression were detected during BoHV-1 and BoHV-5 infection, particularly during latency.
Asunto(s)
Enfermedades de los Bovinos , Infecciones por Herpesviridae , Herpesvirus Bovino 1 , Animales , Bovinos , Infecciones por Herpesviridae/veterinaria , Interferones , Ganglio del Trigémino , Replicación ViralRESUMEN
Temporomandibular joint (TMJ) disorder caused by occlusal trauma is one of the most controversial topics in dentistry. Experimental traumatic occlusion (ETO) induced by metal crowns cemented to mandibular first molars in rats causes a long-lasting nociceptive response. This study aimed to elucidate whether ETO generates an increase in inflammatory mediators in the TMJ. In addition, the impact of ETO on trigeminal ganglia, neurotransmitter release, and satellite glial cell (SGC) activation was investigated. ELISA revealed enhanced inflammatory mediators, including TNF-α, IL-1ß, IL-6, CX3CL1, and ADAM-17 by Western blotting, in periarticular TMJ tissue after 28 d of ETO. In the trigeminal ganglia, ETO groups increased the release of the neurotransmitters substance P and glutamate. Overexpression of the AMPA receptor and upregulation of NMDA were observed in the 0.4- and 0.7-mm ETO groups, respectively, highlighting enhanced neuronal excitation. Increased IL-1ß and COX-2 mRNA levels in the 0.7-mm ETO group confirmed trigeminal ganglia SGC activation. Immunofluorescence and electrophoresis of SGC revealed increased pERK expression in the 0.7-mm ETO group. ERK phosphorylation was shown to be nociceptive specific, with its upregulation occurring in cases of chronic inflammatory pain. Increased PKA mRNA levels were observed in the 0.4-mm ETO group, while CREB mRNA levels were upregulated for both ETO groups. Electrophoresis showed overexpression of sodium channel Nav 1.7 in the 0.7-mm ETO group, while immunofluorescence revealed that Nav 1.7 is expressed in sensory trigeminal ganglia cells. The results of this study suggest that occlusal trauma induces neuroimmune crosstalk, with synthesis of proinflammatory/pronociceptive mediators, which increases neuronal activity in trigeminal ganglia via the activation of an inflammatory response cascade to develop a persistent neuroinflammatory state that leads to central sensitization.
Asunto(s)
Oclusión Dental Traumática , Animales , Oclusión Dental Traumática/metabolismo , Neuroglía/metabolismo , Dolor , Ratas , Articulación Temporomandibular/metabolismo , Ganglio del Trigémino/metabolismoRESUMEN
In mammals, environmental cold sensing conducted by peripheral cold thermoreceptor neurons mostly depends on TRPM8, an ion channel that has evolved to become the main molecular cold transducer. This TRP channel is activated by cold, cooling compounds, such as menthol, voltage, and rises in osmolality. TRPM8 function is regulated by kinase activity that phosphorylates the channel under resting conditions. However, which specific residues, how this post-translational modification modulates TRPM8 activity, and its influence on cold sensing are still poorly understood. By mass spectrometry, we identified four serine residues within the N-terminus (S26, S29, S541, and S542) constitutively phosphorylated in the mouse ortholog. TRPM8 function was examined by Ca2+ imaging and patch-clamp recordings, revealing that treatment with staurosporine, a kinase inhibitor, augmented its cold- and menthol-evoked responses. S29A mutation is sufficient to increase TRPM8 activity, suggesting that phosphorylation of this residue is a central molecular determinant of this negative regulation. Biophysical and total internal reflection fluorescence-based analysis revealed a dual mechanism in the potentiated responses of unphosphorylated TRPM8: a shift in the voltage activation curve toward more negative potentials and an increase in the number of active channels at the plasma membrane. Importantly, basal kinase activity negatively modulates TRPM8 function at cold thermoreceptors from male and female mice, an observation accounted for by mathematical modeling. Overall, our findings suggest that cold temperature detection could be rapidly and reversibly fine-tuned by controlling the TRPM8 basal phosphorylation state, a mechanism that acts as a dynamic molecular brake of this thermo-TRP channel function in primary sensory neurons.SIGNIFICANCE STATEMENT Post-translational modifications are one of the main molecular mechanisms involved in adjusting the sensitivity of sensory ion channels to changing environmental conditions. Here we show, for the first time, that constitutive phosphorylation of the well-conserved serine 29 within the N-terminal domain negatively modulates TRPM8 channel activity, reducing its activation by agonists and decreasing the number of active channels at the plasma membrane. Basal phosphorylation of TRPM8 acts as a key regulator of its function as the main cold-transduction channel, significantly contributing to the net response of primary sensory neurons to temperature reductions. This reversible and dynamic modulatory mechanism opens new opportunities to regulate TRPM8 function in pathologic conditions where this thermo-TRP channel plays a critical role.
Asunto(s)
Membrana Celular/genética , Membrana Celular/metabolismo , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Animales , Células COS , Chlorocebus aethiops , Femenino , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Fosforilación/fisiología , Ganglio del Trigémino/metabolismoRESUMEN
PURPOSE: Satellite glial cells (SGC) surrounding neurons in sensory ganglia can buffer extracellular potassium, regulating the excitability of injured neurons and possibly influencing a shift from acute to neuropathic pain. SGC apoptosis may be a key component in this process. This work evaluated induction or enhancement of apoptosis in cultured trigeminal SGC following changes in intracellular potassium [K]ic. MATERIALS AND METHODS: We developed SGC primary cultures from rat trigeminal ganglia (TG). Purity of our cultures was confirmed using immunofluorescence and western blot analysis for the presence of the specific marker of SGC, glutamine synthetase (GS). SGC [K]ic was depleted using hypo-osmotic shock and 4 mM bumetanide plus 10 mM ouabain. [K]ic was measured using the K+ fluorescent indicator potassium benzofuran isophthalate (PBFI-AM). RESULTS: SGC tested positive for GS and hypo-osmotic shock induced a significant decrease in [K]ic at every evaluated time. Cells were then incubated for 5 h with either 2 mM staurosporine (STS) or 20 ng/ml of TNF-α and evaluated for early apoptosis and late apoptosis/necrosis by flow cytometry using annexin V and propidium iodide. A significant increase in early apoptosis, from 16 to 38%, was detected in SGC with depleted [K]ic after incubation with STS. In contrast, TNF-α did not increase early apoptosis in normal or [K]ic depleted SGC. CONCLUSION: Hypo-osmotic shock induced a decrease in intracellular potassium in cultured trigeminal SGC and this enhanced apoptosis induced by STS that is associated with the mitochondrial pathway. These results suggest that K+ dysregulation may underlie apoptosis in trigeminal SGC.
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Neuroglía , Ganglio del Trigémino , Animales , Apoptosis , Potasio , Ratas , Estaurosporina/farmacologíaRESUMEN
The aim of this work was to investigate the involvement of substance P (SP), osteopontin (OPN), and satellite glial cells (SGC) on photobiomodulation-induced (PBM) antinociceptive effect in an experimental model of dentin hypersensitivity (DH). Rats ingested isotonic drink (ID, pH 2.87) for 45 consecutive days and after this period received PBM irradiation at λ660 nm or λ808 nm (1 J, 3.5 J/cm2, 100 mW, 10 s, 0.028 cm2, continuous wave, 3 consecutive daily sessions), and were evaluated for nociceptive behavior 24, 48, 72 h, and 14 days after laser treatments. ID ingestion induced an increase on thermal sensitivity of DH characteristics in rats that was completely reversed by PBM treatment at both 660 and 808 nm. Immunohistochemical analysis revealed increased SP expression at both dentin-pulp complex (DPC) and trigeminal ganglia (TG) of DH-rats which did not occur in PBM groups by PBM treatment. Also, the increase of glial fibrillary acidic protein (GFAP) observed in the TG of DH-rats was also reversed by PBM treatment. Finally, PBM at both 660 and 808 nm increased OPN expression in the dentin-pulp complex of DH-rats after 14 days of PBM treatment. All in all, this data demonstrates that PBM reverses nociception in a DH experimental model by inhibiting neurogenic inflammation and inducing a regenerative response.
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Sustancia P , Analgésicos , Animales , Sensibilidad de la Dentina , Terapia por Luz de Baja Intensidad , Masculino , Modelos Teóricos , Neuroglía , Nocicepción , Osteopontina , Ratas , Ganglio del TrigéminoRESUMEN
Introducción: Introducción: La compresión percutánea con balón (CPB) es una de las técnicas estándar para el tratamiento de la neuralgia del trigémino. El objetivo de este estudio es evaluar la eficacia de la compresión percutánea con balón (CPB) del ganglio de Gasser y raíz trigeminal en el tratamiento de la neuralgia del trigémino (TN). Métodos: Se usó un estudio observacional analítico de cohorte prospectivo. Un total de 293 pacientes con neuralgia del trigémino fueron tratados con la CPB entre octubre de 2008 y octubre de 2019 en Lima, Perú. Los datos fueron obtenidos de los registros hospitalarios y entrevistas. La CPB se realizó bajo sedación con propofol y remifentanilo. Se administróoxígeno a través de cánula nasal y se monitorizó la frecuencia cardíaca y la presión arterial durante todo el procedimiento. Elprocedimiento se realizó usando fluoroscopia con arco en C para facilitar la introducción de la aguja 14 G hasta que se ingresaal agujero oval y la visualización del catéter Fogarty 4F inflado en el cavum de Meckel. En la posición correcta, generalmenteaparece claramente definido una forma de pera o de reloj de arena después de la inyección de 0.5-1 ml de material decontraste. Resultados: La edad media fue de 64.2 años (rango 27-90). Treinta y seis pacientes (12%) tuvieron otros procedimientosquirúrgicos previos. Doscientos sesenta y dos pacientes (89.4%) experimentaron un alivio inmediato de la neuralgia despuésdel procedimiento. Se obtuvo un balón con forma de pera en 162 casos (55.3%), reloj de arena 73 (24.9%) y oval 58 (19.8%). En 245 pacientes (83.6%) el balón se mantuvo inflado durante 60 - 90 segundos. Es crucial obtener una forma de pera o de reloj de arena porque este es probablemente el factor más importante para obtener un buen alivio del dolor y duradero. Todo el procedimiento dura unos 15 minutos. La hipoestesia hemifacial después del procedimiento fue moderada o severa en el 76.5% de los pacientes. A los tres meses, la mayoría de los pacientes tienen una recuperación significativa en la sensibilidad facial, que continúa recuperándose con el tiempo. Todos los pacientes tuvieron alguna dificultad transitoria para masticar en el lado afectado. Se observó recurrencia en 26 pacientes (9.2%) en un tiempo de seguimiento de 6 meses a 11 años (5.75 años). La forma más común de balón asociada con recurrencia fue la oval (65.4%).Conclusiones: La CPB es técnicamente simple, bien tolerada por los pacientes. La tasa de éxito de la operación es alta. Los pacientes con balón en forma de pera o de reloj de arena obtuvieron los mejores resultados.
Introduction: Percutaneous balloon compression (PBC) is one of the standards techniques for the treatment of trigeminal neuralgia.The objective of this study is to evaluate the efficacy of PBC of the Gasserian ganglion and trigeminal rootlets as treatment for trigeminal neuralgia (TN). Methods: A prospective cohort analytical observational study was used. A total of 293 patients with trigeminal neuralgia were treated with PBC between october 2008 and October 2019 in Lima, Perú. The data were obtained from hospital records and interviews. PBC was performed under sedation with propofol and remifentanil. Oxygen was administered through nasal cannula and the heart rate and blood pressure were monitored throughout the procedure. The procedure is carried out with C-arm fluoroscopy to facilitate the introduction of the 14 G needle until the foramen oval is entered and the visualization of the inflated catheter Fogarty 4F in the Meckel Ìs cave. Once in the right position, a clearly defined pear shape or hourglass is seen after injection of 0.5 1 mL of contrast material. Results: The mean age was 64.2 years (range, 27-90). Thirty-six patients (12%) had other previous surgical procedures. Two hundred sixty-two patients (89.4%) experienced immediate relief from neuralgia following the procedure. A pear-shaped balloon was obtained in 162 cases (55.3%), hourglass 73 (24.9%) and oval 58 (19.8%). In 245 patients (83.6%) the balloon is kept inflated for 6090 seconds. It is crucial to obtain a pear shape or hourglass because this probably is the most significant factor for obtaining good, long-lasting pain relief. The whole procedure takes 15 minutes. Following the procedure, hemifacial hypoesthesia was moderate or severe in 76.5% of patients. Most patients have a significant recovery in facial sensitivity at three months post-procedure and continue to improve over time. All patients faced some transient difficulty chewing in the affected side. Recurrence was observed in 26 patients (9.2%) during a follow-up time of 6 months to 11 years (5.75 years). The most common form of balloon associated with recurrence was oval (65.4%).Conclusions: PBC is a technically simple, well tolerated by patients. The operation success rate is high. Patients with pear or hourglass shape balloon obtained the best results.
Asunto(s)
Humanos , Neuralgia del Trigémino , Terapéutica , Ganglio del Trigémino , Masticación , NeuralgiaRESUMEN
Objetivos: Describir resultados de los últimos 11 años en el tratamiento de neuralgia del trigémino con termocoagulación por radiofrecuencia, analizar variables relacionadas a complicaciones y resultados. Material y Métodos: Estudio retrospectivo, descriptivo, longitudinal, comparativo y analítico. Se analizaron los resultados de los últimos 11 años de nuestro servicio evaluando las temperaturas de las lesiones armando dos grupos, de 65°C-70°C y 71°C-75°C para analizar su relación con resultados y complicaciones. Resultados: Se trataron 59 pacientes en los cuales se realizaron 74 procedimientos, la edad media fue 59.22 años (±13,45). Se observó recidiva en 23 procedimientos con una tasa global de 31%. El tiempo medio de recidiva fue de 28,19 meses (±26,21). El tiempo medio de seguimiento fue de 33,10 meses (±33,49). El tiempo medio de evolución del dolor, previo al primer procedimiento, fue de 5,35 años (±4,37). Analizando los grupos se observó que no existía relación significativamente estadística (p = 0,74) entre el grupo de pacientes de 65ºC-70ºC y el grupo de 71ºC-75ºC y recidiva. No se observó relación estadísticamente significativa entre el grupo de 65ºC-70ºC y el grupo de 71ºC-75ºC y tiempo de recidiva (p=0,12). Se observó más pacientes con hipoestesia inmediata en el grupo de pacientes de 65ºC-70ºC, sin significación estadística (p=0,47). Conclusión: La termocoagulación por radiofrecuencia de ganglio de Gasser es un procedimiento accesible, mínimamente invasivo que demostró buenos resultados y buen manejo del dolor con bajo índice de complicaciones.
Objectives: Describe results of the last 11 years in the treatment of trigeminal neuralgia with radiofrequency thermocoagulation, analyze variables related to complications and results. Methods: Retrospective, descriptive, longitudinal, comparative and analytical study. The results of the last 11 years of our service were analyzed by assessing the temperatures of the lesions by assembling two groups, 65° C-70° C and 71 ° C-75° C to analyze their relationship with results and complications. Results: 59 patients were treated in which 74 procedures were performed; the mean age was 59.22 years (± 13.45). Recurrence was observed in 23 procedures with an overall rate of 31%. The average recurrence time was 28.19 months (± 26.21). The average follow-up time was 33.10 months (± 33.49). The average time of pain evolution, prior to the first procedure, was 5.35 years (± 4.37). Analyzing the groups, it was observed that there was no significant statistical relationship (p = 0.74) between the group of patients from 65ºC-70ºC and the group from 71ºC-75ºC and recurrence. No statistically significant relationship was observed between the 65ºC-70ºC group and the 71ºC-75ºC group and recurrence time (p = 0.12). More patients with immediate hypoaesthesia were observed in the group of patients from 65ºC-70ºC, without statistical significance (p = 0.47). Conclusion: Gasser's ganglion radiofrequency thermocoagulation is an accessible, minimally invasive procedure that demonstrated good results and good pain management with a low complication rate
Asunto(s)
Humanos , Neuralgia del Trigémino , Temperatura , Terapéutica , Ganglio del Trigémino , Electrocoagulación , Manejo del Dolor , NeuralgiaRESUMEN
There is increasing evidence that the toll-like receptor 4 (TLR4) signaling pathway contribute to development of hyperalgesia in the trigeminal system. The aim of the present study was to investigate the role of TLR4 in the trigeminal ganglion (TG) in facial hyperalgesia induced by injection of Lipopolysaccharide (LPS) or intraoral mucosal incision, which is an orofacial postoperative pain model, in male Wistar rats. The TLR4 antagonist (LPS-RS, 20 µg/10 µL) was administrated 30 min before LPS injection into the TG (10 µg/10 µL) or oral mucosa (10 µg/50 µL). In the postoperative pain model, rats were treated with LPS-RS (20 µg/10 µL) into the TG for three consecutive days after the incision. Facial heat and mechanical hyperalgesia were assessed hourly after LPS injection or intraoral incision. In addition, expression of NFκB was assessed in the TG on day 3 after intraoral incision. Our results showed that blockade of TLR4 in the TG attenuated facial heat and mechanical hyperalgesia induced by LPS or by mucosal incision, and that both conditions are associated to increase of phosphorylated NFκB in the TG. In conclusion, the present study suggests that activation of TLR4-NFκB signaling pathway in the TG contributes to the development of facial heat and mechanical hyperalgesia and may contribute to pain in inflammatory oral conditions.
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Hiperalgesia , Receptor Toll-Like 4 , Ganglio del Trigémino , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Transducción de SeñalRESUMEN
OBJECTIVE: To evaluate whether intraganglionic calcitonin gene-related peptide induced differential migraine-like responses in male and female rats. METHODS: Calcitonin gene-related peptide was injected in the trigeminal ganglion of male and female rats followed by assessment of periorbital mechanical allodynia with von Frey hairs. The influence of systemic treatment with sumatriptan or intraganglionic treatment with minocycline and propentofylline was determined on the calcitonin gene-related peptide-induced mechanical allodynia in male and female rats. One additional group was exposed to an aversive light 24 h after calcitonin gene-related peptide priming, followed by evaluation of periorbital mechanical threshold, and another group was tested in the elevated-plus maze. RESULTS: Intraganglionar calcitonin gene-related peptide-induced periorbital mechanical allodynia in female (0.5 to 6 h) and male rats (0.5 to 4 h). Systemic sumatriptan briefly attenuated the mechanical allodynia, but intraganglionar minocycline or propentofylline injection was effective only in male rats. Calcitonin gene-related peptide induced photic sensitivity in female and male rats (lasting 4 h and 1 h, respectively), as well as anxiety-like behavior. CONCLUSIONS: Intraganglionar calcitonin gene-related peptide may play a major role in migraine-like responses, including periorbital mechanical allodynia, light sensitivity and anxiety like-behavior. Female rats are likely to be more susceptible to calcitonin gene-related peptide effects and a better understanding of the sexual dimorphism in calcitonin gene-related peptide signaling may help to improve migraine therapy.
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Péptido Relacionado con Gen de Calcitonina/metabolismo , Hiperalgesia/metabolismo , Trastornos Migrañosos/metabolismo , Ganglio del Trigémino/metabolismo , Animales , Péptido Relacionado con Gen de Calcitonina/farmacología , Femenino , Hiperalgesia/inducido químicamente , Masculino , Trastornos Migrañosos/inducido químicamente , Ratas , Ratas Wistar , Agonistas del Receptor de Serotonina 5-HT1/farmacología , Caracteres Sexuales , Sumatriptán/farmacología , Ganglio del Trigémino/efectos de los fármacosRESUMEN
BACKGROUND: Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine that plays an important role in the early stages of inflammation. In this study, we investigated its role in orofacial discomfort in rats subjected to occlusal dental interference (ODI). METHODS: Female Wistar rats (180-200 g) were divided in three groups (n = 30/group): sham group, without ODI, and two experimental groups with ODI pre-treated with 0.1 mL/kg saline (ODI + SAL) or 5 mg/kg infliximab (ODI + INF) and treated every 3 days. The animals were euthanized after 1, 3, and 7 days. The number of bites and scratches and grimace scale scores were determined daily, and the bilateral trigeminal ganglion was histomorphometrically (neuronal body area) analyzed and submitted for immunohistochemistry for TNF-α, nitric oxide synthesis (NOS) neuronal (nNOS) and inducible (iNOS), peroxisome proliferator-activated receptors (PPAR) y (PPARy) and δ/ß (PPARδ/ß), and glial fibrillary acidic protein (GFAP). One-way/two-way ANOVA/Bonferroni tests were used (P < .05, GraphPad Prism 5.0). RESULTS: ODI + SAL showed a large number of bites (P = .002), scratches (P = .002), and grimace scores (P < .001) in the firsts days, and ODI + INF partially reduced these parameters. The contralateral and ipsilateral neuronal body area was significantly reduced on day 1 in ODI + SAL, but returned to the basal size on days 3 and 7, by increase in TNF-α, nNOS, PPARy, PPARδ/ß, and GFAP immunostaining. The infliximab treatment attenuated these alterations (P < .05). There was no iNOS immunostaining. CONCLUSION: Occlusal dental interference induced transitory orofacial discomfort by trigeminal inflammatory mediator overexpression, and TNF-α blockage attenuated these processes.
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Ganglio del Trigémino , Animales , Citocinas , Femenino , Inflamación , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfaRESUMEN
Capsaicin, an agonist of TRPV1, evokes intracellular [Ca2+] transients and glutamate release from perfused trigeminal ganglion. The spider toxin PnTx3-5, native or recombinant is more potent than the selective TRPV1 blocker SB-366791 with IC50 of 47⯱â¯0.18â¯nM, 45⯱â¯1.18â¯nM and 390⯱â¯5.1â¯nM in the same experimental conditions. PnTx3-5 is thus more potent than the selective TRPV1 blocker SB-366791. PnTx3-5 (40â¯nM) and SB-366791 (3⯵M) also inhibited the capsaicin-induced increase in intracellular Ca2+ in HEK293â¯cells transfected with TRPV1 by 75⯱â¯16% and 84⯱â¯3.2%, respectively. In HEK293â¯cells transfected with TRPA1, cinnamaldehyde (30⯵M) generated an increase in intracellular Ca2+ that was blocked by the TRPA1 antagonist HC-030031 (10⯵M, 89% inhibition), but not by PnTx3-5 (40â¯nM), indicating selectivity of the toxin for TRPV1. In whole-cell patch-clamp experiments on HEK293â¯cells transfected with TRPV1, capsaicin (10⯵M) generated inward currents that were blocked by SB-366791 and by both native and recombinant PnTx3-5 by 47⯱â¯1.4%; 54⯱â¯7.8% and 56⯱â¯9.0%, respectively. Intradermal injection of capsaicin into the rat left vibrissa induced nociceptive behavior that was blocked by pre-injection with either SB-366791 (3 nmol/site i.d., 83.3⯱â¯7.2% inhibition) or PnTx3-5 (100 fmol/site, 89⯱â¯8.4% inhibition). We conclude that both native and recombinant PnTx3-5 are potent TRPV1 receptor antagonists with antinociceptive action on pain behavior evoked by capsaicin.
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Señalización del Calcio/efectos de los fármacos , Capsaicina/farmacología , Dolor Facial/metabolismo , Neuropéptidos/farmacología , Nocicepción/efectos de los fármacos , Fármacos del Sistema Sensorial/farmacología , Canales Catiónicos TRPV/antagonistas & inhibidores , Ganglio del Trigémino/efectos de los fármacos , Acroleína/análogos & derivados , Acroleína/farmacología , Anilidas/farmacología , Animales , Calcio/metabolismo , Cinamatos/farmacología , Modelos Animales de Enfermedad , Ácido Glutámico/efectos de los fármacos , Ácido Glutámico/metabolismo , Células HEK293 , Humanos , Concentración 50 Inhibidora , Masculino , Técnicas de Placa-Clamp , Ratas , Canal Catiónico TRPA1/efectos de los fármacos , Canal Catiónico TRPA1/genética , Canales Catiónicos TRPV/genética , Transfección , Ganglio del Trigémino/metabolismoRESUMEN
The mechanisms underlying temporomandibular disorders following orofacial pain remain unclear. Hydrogen sulfide (H2S), a newly identified gasotransmitter, has been reported to modulate inflammation. Cystathionine γ-lyase (CSE) is responsible for the systemical production of H2S, which exerts both pro- and antinociceptive effects through inflammation. In the current study, we investigated whether the endogenous H2S production pathway contributes to arousal and maintenance of orofacial inflammatory pain, through the investigation of the effects of a CSE inhibitor, propargyglycine (PAG), in a rat CFA (Complete Freund Adjuvant)-induced temporomandibular inflammation model to mimic persistent pain in the orofacial region. For this, rats received either CFA or saline in the temporomandibular joints (TMJs), and after 3 or 14 days, they received a single injection of PAG or saline and were evaluated for nociception with the von Frey and formalin test. Also, pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were analyzed in TMJs and trigeminal ganglion (TG). In this last one, glial cells reactivity was also verified. Endogenous H2S production rate were measured in both, TMJ and TG. Our results indicated decreased allodynia and hyperalgesic responses in rats submitted to CFA after injection of PAG. Moreover, PAG inhibited leucocyte migration to temporomandibular synovial fluid after 3 and 14 days of inflammation. PAG was able to reduce levels of CBS, CSE, TNF-α, and IL-1ß in the TMJ and TG, after 13 days of CFA injection. The observed increased activation of glial cells in the trigeminal ganglia on the 14th day of inflammation can be prevented by the highest dose of PAG. Finally, CBS and CSE expression, and endogenous H2S production rate in the TMJ and TG was found higher in rats with persistent temporomandibular inflammation compared to rats injected with saline and PAG was able to prevent this elevation. Our results elucidated the molecular mechanisms by which H2S exerts its pro-inflammatory and pro-nociceptive role in the orofacial region by alterations in both local tissue and TG.
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Alquinos/uso terapéutico , Glicina/análogos & derivados , Sulfuro de Hidrógeno/metabolismo , Hiperalgesia/tratamiento farmacológico , Inflamación/metabolismo , Dolor/tratamiento farmacológico , Articulación Temporomandibular/metabolismo , Animales , Cistationina gamma-Liasa/antagonistas & inhibidores , Inhibidores Enzimáticos/uso terapéutico , Glicina/uso terapéutico , Interleucina-1beta/metabolismo , Masculino , Neuroglía/efectos de los fármacos , Ratas Wistar , Ganglio del Trigémino/citología , Ganglio del Trigémino/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Apesar dos bovinos serem considerados os hospedeiros naturais do BoHV-1, estudos sorológicos têm sugerido que búfalos podem ser suscetíveis ao BoHV-1 e a outros alfa-herpesvírus geneticamente relacionados. O objetivo deste estudo foi detectar a presença de DNA viral de BoHV-1 em 202 amostras de gânglios trigêmeos de búfalos, pela técnica de semi-nested PCR, para detecção de um segmento do gene codificante da glicoproteína D (gD) do BoHV-1. Além disso, 242 amostras de soro foram analisadas pela técnica de soroneutralização (SN) para a detecção de anticorpos neutralizantes contra BoHV-1, BoHV-5 e BuHV. Todas as amostras clínicas foram coletadas em um matadouro na cidade de Pelotas, RS, Brasil. O DNA de BoHV-1 foi detectado em 61 (30,1%) gânglios, e os resultados da SN demonstraram que 27,6% dos animais apresentaram anticorpos contra, pelo menos, um dos vírus testados. O sequenciamento genômico e a análise de 14 amplicons confirmaram a presença do DNA do BoHV-1 nos tecidos analisados. Em resumo, os resultados indicam que o BoHV-1 está distribuído em rebanhos bubalinos provenientes da região Sul do Brasil. Entretanto, são necessárias investigações adicionais, no sentido de elucidar o papel exato dos búfalos na epidemiologia das infecções pelo BoHV-1.(AU)
Although bovines are natural hosts for BoHV-1, serologic studies in several countries have suggested that buffaloes (Bubalus bubalis) may be susceptible to BoHV-1 and other genetically related alphaherpesvirus. This study aimed to investigate the presence of BoHV-1 DNA in trigeminal ganglia from 202 buffaloes by a semi-nested PCR to amplify partially the glycoprotein D (gD) gene of BoHV-1. Additionally, 242 serum samples were tested by serum neutralization (SN) for the detection of antibodies against BoHV-1, BoHV-5 and BuHV. All clinical samples were collected in a slaughterhouse located in Pelotas, RS, Brazil. BoHV-1 DNA was detected in 61 (30.1%) of the samples and SN revealed 27.6% of the animals with neutralizing antibodies against at least one of the tested viruses. Nucleotide sequencing of 15 amplicons followed by BLAST analysis confirmed the presence of BoHV-1 DNA in the analyzed tissues. Taken together, these data indicate that BoHV-1 infection is distributed in buffaloes in southern Brazil. However, the role of buffaloes in the BoHV-1 epidemiology needs further investigation.(AU)
Asunto(s)
Animales , ADN Viral/análisis , Búfalos/virología , Ganglio del Trigémino/virología , Infecciones por Herpesviridae/veterinaria , Herpesvirus Bovino 1/genética , Reacción en Cadena de la Polimerasa/veterinariaRESUMEN
Apesar dos bovinos serem considerados os hospedeiros naturais do BoHV-1, estudos sorológicos têm sugerido que búfalos podem ser suscetíveis ao BoHV-1 e a outros alfa-herpesvírus geneticamente relacionados. O objetivo deste estudo foi detectar a presença de DNA viral de BoHV-1 em 202 amostras de gânglios trigêmeos de búfalos, pela técnica de semi-nested PCR, para detecção de um segmento do gene codificante da glicoproteína D (gD) do BoHV-1. Além disso, 242 amostras de soro foram analisadas pela técnica de soroneutralização (SN) para a detecção de anticorpos neutralizantes contra BoHV-1, BoHV-5 e BuHV. Todas as amostras clínicas foram coletadas em um matadouro na cidade de Pelotas, RS, Brasil. O DNA de BoHV-1 foi detectado em 61 (30,1%) gânglios, e os resultados da SN demonstraram que 27,6% dos animais apresentaram anticorpos contra, pelo menos, um dos vírus testados. O sequenciamento genômico e a análise de 14 amplicons confirmaram a presença do DNA do BoHV-1 nos tecidos analisados. Em resumo, os resultados indicam que o BoHV-1 está distribuído em rebanhos bubalinos provenientes da região Sul do Brasil. Entretanto, são necessárias investigações adicionais, no sentido de elucidar o papel exato dos búfalos na epidemiologia das infecções pelo BoHV-1.(AU)
Although bovines are natural hosts for BoHV-1, serologic studies in several countries have suggested that buffaloes (Bubalus bubalis) may be susceptible to BoHV-1 and other genetically related alphaherpesvirus. This study aimed to investigate the presence of BoHV-1 DNA in trigeminal ganglia from 202 buffaloes by a semi-nested PCR to amplify partially the glycoprotein D (gD) gene of BoHV-1. Additionally, 242 serum samples were tested by serum neutralization (SN) for the detection of antibodies against BoHV-1, BoHV-5 and BuHV. All clinical samples were collected in a slaughterhouse located in Pelotas, RS, Brazil. BoHV-1 DNA was detected in 61 (30.1%) of the samples and SN revealed 27.6% of the animals with neutralizing antibodies against at least one of the tested viruses. Nucleotide sequencing of 15 amplicons followed by BLAST analysis confirmed the presence of BoHV-1 DNA in the analyzed tissues. Taken together, these data indicate that BoHV-1 infection is distributed in buffaloes in southern Brazil. However, the role of buffaloes in the BoHV-1 epidemiology needs further investigation.(AU)