Efecto de la dibucaína sobre la SERCA del músculo pterigoideo interno / Drug action of dibucaine on the SERCA from medial pterygoid muscle

Objetivo: Determinar el efecto del anestésico local di-bucaína sobre las principales isoformas de la SERCA (calcio ATPasa de retículo sarco-endoplásmico) pre-sentes en músculo pterigoideo interno. Métodos: Se aislaron por centrifugación diferencial membranas de retículo sarcoplásmico de pterigoideo interno de conejo neozelandés macho (n=5). Se separaron las isoformas SERCA1a, 2a y 2b por cromatografía de afinidad. Se determinó in vitro la actividad enzimá-tica en presencia de diferentes concentraciones de dibucaína (0-90 mM) por el método de Fiske y Subba-row, realizando 5 experimentos por duplicado y en paralelo para cada isoforma. Se calculó la media y ES de la CI50 (mM) del anestésico para cada isofor-ma y éstas se compararon por ANOVA de una vía (p<0,05), y prueba Student-Newman-Keuls de com-paraciones múltiples. Resultados: Dibucaína inhibió la actividad enzimática en función de su concentra-ción en las tres isoformas en estudio. Las CI50 fueron: SERCA1a 20,02 ± 0,64 mM, SERCA2a 15,03 ± 0,52 mM y SERCA2b 16,00 ± 0,51 mM y resultaron signi-ficativamente diferentes (F2,27 = 11,08, p<0,001). La prueba post hoc identificó diferencias significativas entre SERCA1a y 2a, 1a y 2b. El efecto inhibitorio re-sultó significativamente mayor sobre las isoformas 2a y 2b, cuya presencia es sustancialmente mayor en músculos masticadores. Conclusión: La dibucaína inhibe a la SERCA de pterigoideo interno a concen-traciones menores que las usadas en clínica médica (29 mM). Es un anestésico local con potencial efecto miotóxico derivado de la inhibición de la SERCA (AU)

Aim: To test the effect of the local anesthetic dibu-caine on the main isoforms of the SERCA (sarco-endosplasmic reticulum calcium-ATPase) in medial pterygoid muscle. Methods: Sarcoplasmic reticulum membranes from male New Zealand rabbits (n=5) were isolated from medial pterygoid muscle by ul-tracentrifugation. The isoforms SERCA1a, 2a and 2b were separated using high affinity chromatography. In vitro enzymatic activity determinations were per-formed in the presence of different dibucaine con-centrations (0-90 mM) using the colorimetric method described by Fiske & Subbarow. Five assays in dupli-cate and run in parallel were performed for each of the isoforms. Mean and SEM of the IC50 (mM) for the effect of the anesthetic on each isoform were calcu-lated and compared by one-way ANOVA (p<0.05), and Student-Newman-Keuls multiple comparisons test. Results: Dibucaine inhibited the enzymatic activity in a concentration-dependent manner for the three studied isoforms. The IC50 values were: SERCA1a 20.02 ± 0.64 mM, SERCA2a 15.03 ± 0.52 mM and SER-CA2b 16.00 ± 0.51 mM. The values were significantly different (F2.27 = 11.08, p<0.001). The post hoc test revealed significant differences between SERCA1a and 2a, 1a and 2b. The inhibitory effect was signifi-cantly higher on 2a and 2b isoforms, whose presence is substantially higher in masticatory muscles. Con-clusion: Dibucaine inhibits SERCA in medial pterygoid muscle at concentrations lower than those used in clinical medicine (29 mM). It is a potentially myotoxic local anesthetic whose toxic effect may derive from SERCA inhibition (AU)

A Novel Injection Technique to the Lateral Pterygoid Muscle for Temporomandibular Disorders: A Cadaveric Study.

BACKGROUND: Lateral pterygoid muscle activity is associated with the pathological mechanisms of some temporomandibular disorders. The authors aimed to define and demonstrate a novel, practical, and safe technique for botulinum toxin type A injection to the lateral pterygoid muscle based on their findings. Their secondary aims were to standardize the injection pattern according to the variations of the lateral pterygoid muscle and its surrounding anatomical structures, and to establish its advantages over intraoral injection. METHODS: Twenty cadaver heads were dissected. The lateral pterygoid muscle and its surrounding structures were investigated for anatomical variations. Based on these findings, a standardized extraoral injection protocol was defined and compared with the intraoral technique for accuracy and safety. RESULTS: The average depth of the lateral pterygoid plate from the skin surface was 49.9 ± 2.2 mm, and the mean width of the lateral pterygoid plate was 10.5 ± 3.9 mm. The extraoral injection approach based on the location of the maxillary tuberosity, tragus, and lateral pterygoid plate was consistent in all dissections for the accuracy of the intramuscular injection. In the intraoral approach, standardization of the entry point of the needle through the oral mucosa is difficult, which makes adjustment of the depth of the injection challenging while increasing the risk of neurovascular injury. CONCLUSIONS: The clinical significance of the lateral pterygoid muscle makes it worthwhile to implement minimally invasive treatments before considering more invasive options. The authors define a safe, accurate, and reliable approach with ease of administration in patients with temporomandibular disorders.

Extraoral Versus Intraoral Botulinum Toxin Type A Injection for Management of Temporomandibular Joint Disc Displacement With Reduction.

: The present study was conducted to compare between extraoral and intraoral approach for botulinum toxin type A (BTX-A) injection into the lateral pterygoid muscle (LPM) in patients suffering from anterior disc displacement with reduction (ADDWR).Fourteen patients suffering from ADDWR were included in this prospective cohort study. Patients were enrolled randomly into 2 groups according to injection approach; where extraoral used in group I, while intraoral approach used in group II. The LPM was injected with 20 IU BTX-A under electromyography (EMG) guidance. Postoperative evaluation of the patients included: mouth opening assessment, LPM tenderness, temporomandibular joint TMJ (clicking), and tenderness. The LPM insertional EMG activity was assessed. Also, magnetic resonance imaging (MRI) was performed to evaluate disc position. Descriptive and inferential analysis was conducted to compare between groups.There was significant patient's convenience during injection and significant injection time reduction in group II. A slight decrease in mouth opening immediate post-injection followed by significant improvement from 8th weeks post-injection was reported in both approaches. There was a significant improvement in TMJ clicking from 1st-week post-injection with no group difference. The EMG assessment documented LPM hyperactivity pre-injection followed by significantly decreased muscle activity at 8 and 16 weeks post-injection without statistical difference. The MRI showed no change in disc position after injection. CONCLUSION:: The BTX-A injection into LPM is a simple technique that can be used with high success and low complication rate for treatment of ADDWR. The intraoral approach was superior to the extraoral concerning patient convenience and injection duration with no statistical difference regarding other clinical outcomes.

Electromyography assisted application of botulinum toxin in pterygoid musculature for the treatment of masticatory myofascial pain / Aplicación de toxina botulínica en musculatura pterigoidea asistida con electromiografía para tratamiento del dolor miofascial

AIM: To evaluate the efficacy of botulinum toxin A injection (BTA) in the lateral pterygoid muscles assisted by electromyography (EMG) for the treatment of masticatory myofascial pain (MMP). MATERIAL AND METHODS: We conducted a retrospective study of 31 patients diagnosed of MMP who were treated by infiltration of botulinum toxin A in 1, 2 or 3 times, in the lateral and medial pterygoid muscles by electromyographic control of the puncture site. We assessed the treatment effectiveness in pain intensity decrease by numerical scales (NS) and categorical scales (CS). The impact of pathology on its quality of life, the decrease of demand for analgesic drugs, and the duration of BTA effect and its side effects were also valued. RESULTS: The mean decrease in pain after treatment was 4.9 +/- 2.9 points in NS. A statistical decrease of the pain (p = 0.01) can be shown after treatment. There is no statistical relationship between greater improvement after the administration of a greater number of injections. However, there is a significant improvement in the decrease of the pain in CS (p = 0.028) after the administration of several injections. There is also a significant decrease (p = 0.012) of the use of analgesic medication post-treatment. CONCLUSIONS: EMG assisted pterygoid muscles infiltration of BTA is effective in the treatment of MMP; it improves quality of life and decreases the consumption of health resources

OBJETIVO: Evaluar la eficacia de la inyección de toxina botulínica A (TBA) en los músculos pterigoideos guiada por electromiografía (EMG) para el tratamiento del dolor miofascial masticatorio. MATERIAL Y MÉTODOS: Realizamos un estudio retrospectivo de 31 pacientes diagnosticados de dolor miofascial de origen masticatorio a los que se le administró TBA en los músculos pterigoideos laterales y mediales guiada por EMG. Se evaluó la efectividad por disminución de intensidad del dolor mediante escalas numéricas (EN) y escalas categóricas (EC). Además, se determinó el impacto de esta patología en su calidad de vida, la duración del tratamiento y la disminución de la demanda de analgésicos. RESULTADOS: La disminución media del dolor en la EN tras tratamiento fue de 4,9 +/- 2,9 puntos. Se observó una disminución estadística del dolor (p < 0,01) después del tratamiento. No existe una relación estadística entre una mejoría mayor después de la administración de un mayor número de inyecciones. Sin embargo, hay una mejora significativa en la disminución del dolor en la CS (p = 0,028) después de la administración de varias inyecciones; así como una disminución significativa del uso de medicación analgésica posttratamiento (p = 0,012). CONCLUSIONES: La administración de TBA guiada por EMG en los músculos pterigoideos es eficaz en el tratamiento del dolor miofascial masticatorio, mejor la calidad de vida y se consigue una disminución del consumo de analgésicos postratamiento

A Cadaveric Study of Ultrasound-Guided Maxillary Nerve Block Via the Pterygopalatine Fossa: A Novel Technique Using the Lateral Pterygoid Plate Approach.

BACKGROUND AND OBJECTIVES: This study aimed to describe and assess the accuracy and feasibility of a novel technique for ultrasound-guided maxillary nerve block using the lateral pterygoid plate (LPP) approach via the pterygopalatine fossa (PPF) in a soft cadaveric model. METHODS: Ten soft cadavers were studied. The curved array ultrasound transducer probe was applied over 1 side of the face of the cadavers in the open-mouth posture. It was placed transversely below the zygomatic arch for identifying the border of the maxillary tuberosity and the LPP. We tilted the curve probe from the caudal to the cranial direction until the uppermost part of the PPF was identified. The in-plane needle approach was used from the anterior-to-posterior and lateral-to-medial directions through the fossa, and 3 mL of methylene blue dye was injected. RESULTS: The spread of injectate after ultrasound-guided maxillary nerve block using the LPP approach was successfully performed in all cadavers as demonstrated by visualized moderate to marked traces of methylene blue within the PPF. No accidental injections in the maxillary arteries or facial nerves were observed. CONCLUSIONS: This cadaveric study suggests that ultrasound-guided maxillary nerve block using the LPP approach via the PPF has a high degree of accuracy and feasibility. Further studies are required to confirm its efficacy and safety for clinical application.

Computer-Aided Design/Computer-Assisted Manufacture-Derived Needle Guide for Injection of Botulinum Toxin into the Lateral Pterygoid Muscle in Patients with Oromandibular Dystonia.

AIMS: To evaluate the effectiveness and safety of botulinum toxin administration into the inferior head of the lateral pterygoid muscle of patients with jaw opening dystonia by using a computer-aided design/computer-assisted manufacture (CAD/CAM)-derived needle guide. METHODS: A total of 17 patients with jaw opening dystonia were enrolled. After the patient's computed tomography (CT) scan was imported and fused with a scan of a plaster cast model of the maxilla, the optimal needle insertion site over the lateral pterygoid muscle was determined using the NobelClinician software. A total of 13 patients were injected both with and without the guide, and 4 patients underwent guided injection alone. The therapeutic effects of botulinum toxin injection and its associated complications were statistically compared between the guided and unguided procedures using paired t test. RESULTS: Botulinum toxin therapy was performed 42 and 32 times with and without the guides, respectively. The needle was easily inserted without any complications in all procedures. There was a significant difference (P < .001) between the mean comprehensive improvements observed with (66.3%) and without (54.4%) the guides. CONCLUSION: The findings suggest that the use of needle guides during the injection of botulinum toxin into the inferior head of the lateral pterygoid muscle is very useful for aiding the accurate and safe administration of botulinum toxin therapy for jaw opening dystonia.

A Novel Technique of Ultrasound-Guided Selective Mandibular Nerve Block With a Lateral Pterygoid Plate Approach: A Cadaveric Study.

BACKGROUND AND OBJECTIVES: We aimed to describe a novel technique of ultrasound-guided selective mandibular nerve block with a lateral pterygoid plate (LPP) approach and to assess its feasibility and accuracy in a soft cadaver model. METHODS: Ten soft cadavers were studied. A curved array ultrasound transducer was applied over 1 side of the face of the cadaver, in an open-mouth position. The transducer was placed transversely below the zygomatic arch and tilted in the caudal-to-cranial direction to identify the boundary of the LPP. The needle was inserted in-plane, in an anterior-to-posterior direction, into the posterior border of the uppermost part of the LPP, and 3 mL of methylene blue was injected. RESULTS: Mandibular nerve block was successfully performed in all 10 cadavers using an LPP approach under ultrasound guidance. The mandibular nerve and its branches were seen to be stained with methylene blue in all cadaveric specimens. No accidental injection into the facial nerve or maxillary artery was observed. CONCLUSIONS: This cadaveric study suggests that this novel technique, using an LPP approach under ultrasound guidance, is helpful for selective mandibular nerve block, with high accuracy and feasibility. Further studies are required to establish its safety and efficacy for clinical application. CLINICAL TRIAL REGISTRATION: This study was registered at the Thai Clinical Trials Registry (ClinicalTrials.in.th), identifier TCTR20160601004.

Differential Effect of Articaine on Sarcoendoplasmic Reticulum Calcium Adenosine Triphosphatase of Medial Pterygoid Muscle.

AIMS: To determine the effect of articaine on sarcoendoplasmic reticulum calcium adenosine triphosphatase (SERCA) isoforms of the medial pterygoid muscle. METHODS: Native SERCA from the medial pterygoid muscles of 24 rabbits was isolated by ultracentrifugation, and its isoforms were purified by chromatography and assessed by enzyme-linked immunosorbent assay (ELISA). SERCA activity and calcium transport capability were determined by using colorimetric and radioisotopic methods. The mean ± standard deviation (SD) half maximal inhibitory concentration (IC50) of articaine was determined for each isoform, and these values were compared by using analysis of variance (ANOVA) (P < .05). RESULTS: The native SERCA preparation consisted of 34% SERCA1a, 53% SERCA2a, 10% SERCA2b, and 3% combined SERCA3 and SERCA1b. Articaine caused inhibition of activity and calcium uptake in the native SERCA preparation and in each of the purified isoforms. The IC50 (mM) values for enzymatic activity were: SERCA1a 22.0 ± 2.3 > SERCA2a 16.4 ± 2.4 > SERCA2b 11.3 ± 1.9, and 15.1 ± 2.1 for native SERCA. For calcium transport, IC50 values were: SERCA1a 31.1 ± 3.3 > SERCA2a 24.8 ± 1.8 > SERCA2b 21.5 ± 1.5, and 25.2 ± 3.2 for native SERCA. IC50 values for inhibition of enzymatic activity were significantly different among the purified isoforms, but only the value obtained for SERCA1a was significantly different compared to native SERCA. For inhibition of calcium transport, IC50 values for both SERCA2a and SERCA2b differed significantly compared to SERCA1a, and the value for SERCA1a was significantly different compared to native SERCA. The most articaine-sensitive isoform was SERCA2b, and the native preparation showed sensitivity similar to SERCA2a. CONCLUSION: The differential inhibition of articaine on medial pterygoid SERCA isoforms is evident at concentrations lower than used in current dental practice (125 mM) and accounts for anesthetic myotoxicity. Muscle relaxation likely becomes impaired as a result of increased calcium levels in the myoplasm due to the decreased activity and calcium transport caused by the inhibition of SERCA.

Management of oromandibular dystonia on a chorea acanthocytosis: a brief review of the literature and a clinical case.

BACKGROUND: Chorea acanthocytosis is an extremely rare neurodegenerative condition characterized by neuropsychiatric disturbances, movement disorders, neuropathy, seizures, and acanthocytosis. In this case report, the authors will present the management of the oromandibular movement disorders associated with this disease. CASE DESCRIPTION: This case report describes the focal management of the severe orofacial manifestations associated with this condition. The therapeutic approach adopted to reduce the severe oromandibular movements, dysphagia, and the numerous oral ulcers was selective electromyography (EMG)-guided botulinum toxin application to the inferior head of the lateral pterygoid muscles and masseters. This would be applied to control severe and sudden oromandibular dystonia. RESULTS: Through this procedure, the authors were able to reduce these severe oral manifestations, which had a major impact on the patient's quality of life, and temporarily improve vital functions, such as mastication, deglutition, and speech articulation. CONCLUSIONS: Electromyography-guided botulinum toxin application may be a useful tool in the multimodal management of this condition.

Recurrent TMJ Dislocation Managed with Botulinum Toxin Type A Injections in a Pediatric Patient.

Chronic recurrent temporomandibular joint (TMJ) dislocation is an uncommon condition that is painful and distressing to patients and uniquely challenging for clinicians. Sustained TMJ dislocation is not amenable to manual reduction alone when the etiology is muscular in nature. The purpose of this report was to describe the case of a child presenting with recurring temporomandibular joint dislocation secondary to muscle hyperactivity of unknown etiology that was managed with injections of botulinum toxin type A into the inferior lateral pterygoid muscles. The use of this peripheral antispasmoic neurotoxin is a reasonable, safe, and conservative, palliative treatment option for pediatric patients suffering from chronic recurring TMJ dislocation.

Botulinum injection for the management of myofascial pain in the masticatory muscles. A prospective outcome study.

We prospectively analysed the outcome after botulinum injection in patients who did not recover after conservative measures to manage masticatory myofascial pain, and who were not willing to take low dose tricyclic antidepressants as a muscle relaxant. We prospectively 62 patients were assessed with visual analogue scores (VAS) for pain on the affected side before, and 6 weeks after botulinum injection(s) (50 units Dysport in up to 3 sites), and measured mouth opening in mm. Of those treated 49 (79%) showed at least some improvement (pain reduced by more than 25%). Patients reported more than a 90% reduction in the VAS for 25 (30%) of the 84 sides of the face treated. Only 22 of the 62 patients had more than one course of treatment to the same side. Interincisal distance improved by a mean/median of 0.9 mm (p<0.03) after treatment. Side effects included 3 cases of temporary weakness of a facial muscle. Ranking the VAS pain scores using the Wilcoxon test before and after injection showed a significant reduction in pain (median change -29.5, interquartile range -53 to -16, p<0.0001). The treatment significantly improved patients' pain scores and the overall mean/median reduction in pain was 57%. Botulinum injection does not guarantee complete resolution of myofascial pain, but it usually has some beneficial effect in improving the symptoms, and should be considered as an alternate treatment for masticatory myofascial pain if conservative methods have failed.

Neurogenic temporomandibular joint dislocation treated with botulinum toxin: report of 4 cases.

Many patients suffer recurrent episodes of temporomandibular joint (TMJ) dislocation due to an excess of muscle contraction or spasticity in the depressor muscles of the jaw. The manual repositioning using the Nelaton maneuver is the first treatment. Occasionally, it may be necessary to use sedation or general anesthesia to achieve the desired muscle relaxation. In case of recurrence, surgical treatment is indicated. One nonsurgical method of treatment is the local infiltration of botulinum toxin type A. We present 4 cases of recurrent TMJ dislocation in patients suffering from conditions of neurologic origin, with considerable motor deterioration, treated with local infiltration of botulinum toxin type A. In conclusion, the injection of botulinum toxin type A is an effective method in cases of neurogenic TMJ dislocation, with low morbididty and side effects, improving patients' quality of life.

Long-term efficacy of botulinum toxin type A for the treatment of habitual dislocation of the temporomandibular joint.

Injection of botulinum toxin type A (BTX-A) into the lateral pterygoid muscles is a recently reported treatment for habitual dislocation of the temporomandibular joint (TMJ). We report five cases of dislocation in elderly patients with neurological or other severe systemic disease, and their successful treatment with one injection of BTX-A into the lateral pterygoid muscles. This is a relatively conservative option. Injection into the muscle is straightforward and can be done in outpatients with few complications. We recommend it as the first choice for patients with habitual dislocation and systemic or neurological diseases, particularly in the elderly.

Oromandibular dystonia and hormonal factors: twelve years follow-up of a case report.

Oromandibular dystonia (OMD) is a focal neurological movement disorder characterized by involuntary sustained and often painful muscle contraction, usually producing repetitive movements or abnormal positions of the mouth, jaw and/or tongue. We report on a 30-year-old woman affected with OMD with a 12-year follow-up. Focal dystonia involved an involuntary activity of the lateral pterygoid muscles causing forceful jaw displacement in the maximal protrusive position. These episodes initially occurred during jaw function and increased up to an open-lock with bilateral pre-auricular pain. Dystonic spasms were absent during sleep and were reduced temporarily by sensory tricks. Treatment with botulinum toxin type A (BTX) was performed during three different sessions over a 1-year period. Electromyographic-guided BTX injections into the lateral pterygoid muscles were given with cannula electrodes. Botox reduced the involuntary activity of the muscles. Recurrence and exacerbation of dystonic symptoms occurred during the two pregnancies and completely disappeared immediately after both deliveries with prolonged symptom-free periods. During the last 8 years, the patient had a slight relapse of symptoms during flu attacks, periods of stress and during menses. The temporal pattern of these symptoms indicates a possible relationship between OMD and hormonal factors.

Management of dystonia of the lateral pterygoid muscle with botulinum toxin A.

Oromandibular dystonia (OMD) is a rare neurological condition infrequently seen by oral and maxillofacial surgeons which may result in inappropriate deviation of the mandible, subluxation and intraoral soft tissue trauma. A case is presented of a patient suffering from spasmodic torticollis and lateral pterygoid dystonia and currently under treatment with botulinum A toxin (Botox) injections. Botox has emerged as the most effective form of symptomatic treatment for abnormabilities in muscle movement, namely dystonia with oromandibular symptoms.

Efficacy of botulinum toxin in treating myofascial pain in bruxers: a controlled placebo pilot study.

The present investigation is a preliminary double-blind, controlled placebo, randomized clinical trial with a six month follow-up period. The study aimed to assess the efficacy of type A botulinum toxin (Botox, Allergan, Inc. Irvine, CA) to treat myofascial pain symptoms and to reduce muscle hyperactivity in bruxers. Twenty patients (ten males, ten females; age range 25-45) with a clinical diagnosis of bruxism and myofascial pain of the masticatory muscles were enrolled in a double-blind, controlled placebo, randomized clinical trial, with a treatment group (ten subjects treated with botulinum toxin injections- BTX-A) and a control group (ten subjects treated with saline placebo injections). A number of objective and subjective clinical parameters (pain at rest and during chewing; mastication efficiency; maximum nonassisted and assisted mouth opening, protrusive and laterotrusive movements; functional limitation during usual jaw movements; subjective efficacy of the treatment; tolerance of the treatment) were assessed at baseline time and at one week, one month, and six months follow-up appointments. Descriptive analysis showed that improvements in both objective (range of mandibular movements) and subjective (pain at rest; pain during chewing) clinical outcome variables were higher in the Botox treated group than in the placebo treated subjects. Patients treated with BTX-A had a higher subjective improvement in their perception of treatment efficacy than the placebo subjects. Differences were not significant in some cases due to the small sample size. Results from the present study supported the efficacy of BTX-A to reduce myofascial pain symptoms in bruxers, and provided pilot data which need to be confirmed by further research using larger samples.