The safety of botulinum neurotoxin type A's intraarticular application in experimental animals.

In vivo studies of botulinum neurotoxin type A (BoNT-A) enabled characterization of its activity in the nociceptive sensory system separate from its preferred action in motor and autonomic nerve terminals. However, in the recent rodent studies of arthritic pain which employed high intra-articular (i.a.) doses (expressed as a total number of units (U) per animal or U/kg), possible systemic effects have not been conclusively excluded. Herein we assessed the effect of two pharmaceutical preparations, abobotulinumtoxinA (aboBoNT-A, 10, 20, and 40 U/kg corresponding to 0.05, 0.11, and 0.22 ng/kg neurotoxin) and onabotulinumtoxinA (onaBoNT-A, 10 and 20 U/kg corresponding to 0.09 and 0.18 ng/kg, respectively) injected into the rat knee, on safety-relevant readouts: digit abduction, motor performance and weight gain during 14 days post-treatment. The i. a. toxin produced dose-dependent impairment of the toe spreading reflex and rotarod performance, which was moderate and transient after 10 U/kg onaBoNT-A and ≤20 U/kg aboBoNT-A doses, and severe and long-lasting (examined up to 14 days) after ≥20 U/kg of onaBoNT-A and 40 U/kg aboBoNT-A. In addition, lower toxin doses prevented the normal weight gain compared to controls, while higher doses induced marked weight loss (≥20 U/kg of onaBoNT-A and 40 U/kg aboBoNT-A). Commonly employed BoNT-A formulations, depending on the doses, cause local relaxation of the surrounding muscles and systemic adverse effects in rats. Thus, to evade possible toxin unwanted local or systemic spread, careful dosing and motor testing should be mandatory in preclinical behavioral studies, irrespective of the sites and doses of toxin application.

Myomodulation using hyaluronic acid fillers as an efficient and innovative treatment for gummy smile: A case report.

Myomodulation (MyoMo) using hyaluronic acid (HA) fillers can be considered as a novel aesthetic treatment for gummy smile (GS). However, literature is still lacking information about this procedure. For this reason, the aim of the present case report was to describe a technique for MyoMo with HA as an efficient alternative for the management of GS. A 36-year-old male patient attended to our clinic complaining about excessive gingival exposure when smiling. After a clinical and digital assessment, poor bone support was observed in the premaxilla area, resulting in an increasing contraction of the levator labii superioris alaeque nasi and levator anguli oris. A multilayer approach with HA filling was performed in order to impair muscle movement and limit excessive lip elevation. As a result, a reduction on the elevation of the upper lip while smiling was achieved, and an improvement on GS was achieved. Thus, it can be proposed that Myomo with HA acid may be an effective treatment for GS, with lasting and satisfactory results. However, high-quality studies are required in order to compare patient's satisfaction with this treatment and any other possible alternative.

Antinociceptive Actions of Botulinum Toxin A1 on Immunogenic Hypersensitivity in Temporomandibular Joint of Rats.

Botulinum neurotoxin type A1 (BoNT-A) reduces the peripheral peptide and cytokine upregulation in rats with antigen-evoked persistent immunogenic hypersensitivity (PIH) of the temporomandibular joint (TMJ). Herein, we examined the effects of two preparations of BoNT-A, abobotulinumtoxinA (aboBoNT-A; Dysport) and onabotulinumtoxinA (onaBoNT-A; Botox), on spontaneous and evoked nociceptive behaviors, as well as on central neuronal and astroglial activation. The antigen-evoked PIH was induced in rats via repeated systemic and unilateral intra-articular (i.a.) injections of methylated bovine serum albumin (mBSA). Rats were subsequently injected with unilateral i.a. aboBoNT-A (14 U/kg), onaBoNT-A (7 U/kg), or the vehicle (saline). After i.a. treatments, spontaneous and mechanically evoked nocifensive behaviors were assessed before and after the low-dose i.a. formalin (0.5%) challenge. The central effects of BoNT-A were assessed by an immunohistochemical analysis of cleaved synaptosomal-associated protein 25 (cSNAP-25) presence, c-Fos, GFAP, and CGRP expression in the trigeminal nucleus caudalis (TNC). Both BoNT-A preparations similarly reduced the formalin-induced spontaneous pain-related behaviors and mechanical allodynia of the hypernociceptive rats. Likewise, their effects were associated with the central occurrence of cSNAP-25 and reduction of c-Fos and GFAP upregulation in the TNC. BoNT-A antinociceptive activity on the PIH is associated with the toxin axonal transport to trigeminal sensory areas and reduction of neuronal and glial activation in central nociceptive regions.

Muscle Function Recovery Following Botulinum Toxin Type A Facial Injections: A Case Managed With Photobiomodulation Therapy.

Introduction: Aesthetic applications of botulinum toxin type A (BoNT-A) may lead to some complications, including unwanted muscle paralysis. Moreover, BoNT-A effects may last several months, and there is no medical intervention so far to accelerate muscle function recovery. Case Report: A female patient with a movement disorder of the mimic muscles resulting from BoNT-A injections received daily sessions of photobiomodulation therapy (PBMT). A fast improvement in both facial asymmetry and muscle function was noted within a few weeks. After nine weeks, almost complete recovery was achieved. Conclusion: According to the current case, PMBT seems to be an effective intervention to accelerate muscle function recovery following BoNT-A use.

3D stereophotogrammetry quantification for tissue repositioning using Botulinum toxin A: a case report / Quantificação por estereofotogrametria 3D para reposicionamento tecidual com Toxina botulínica A: relato de caso

Hereby, we objectively assessed the outcomes of a facial-lifting procedure with Botulinum toxin type A (BoNT-A) using a 3D stereophotogrammetry quantification (3D-SQ). A 46-year-old female patient received a full face BoNT-A treatment in a total dose of 180 Speywood Units (sU). Frontal, lateral and oblique photographs were taken before and 20 days after treatment, at rest and during mimic movements. Also, a facial scanning was performed before and 20 days after BoNT-A injections. The results were analyzed using a 3D-SQ software. The photographs showed a decrease in expression lines and dynamic wrinkles. In addition, a better-defined jawline and volume gain in the midface area with improvement of the profile appearance, due to the reduction of the sagging skin under the chin, was observed. The 3D-SQ showed volume gains of 1.17 ml on the right and of 1.59 ml on the left cheekbone areas, due to the cranially soft-tissue repositioning. In addition, a decrease in the volume of melomental folds areas (0.27ml on the right and 0.41 ml on the left side) was reported, compatible to the above-mentioned volume gain. Measurements considering cephalometric points showed a decrease in the total facial height (distance from Trichion to Mental points), suggesting a soft tissue dislocation in an upward direction. Finally, this case report showed quantitative results that can evidence the role of BoNT-A in facial- lifting procedures. These results reinforce the importance of using a 3D-SQ to assess the outcomes of BoNT-A and, probably, other aesthetic procedures.(AU)

No presente estudo avaliamos objetivamente os resultados de um procedimento de lifting facial com toxina botulínica tipo A (BoNT-A) usando uma quantificação de estereofotogrametria 3D (3D-SQ). Uma paciente do sexo feminino de 46 anos recebeu um tratamento facial completo com BoNT-A em uma dose total de 180 unidades Speywood (sU). Fotografias frontais, laterais e oblíquas foram tomadas antes e 20 dias após o tratamento, em repouso e durante os movimentos mímicos. Além disso, um escaneamento facial foi realizado antes e 20 dias após as injeções de BoNT-A. Os resultados foram analisados por meio de um software 3D-SQ. As fotografias mostraram uma diminuição das linhas de expressão e rugas dinâmicas. Além disso, observou-se um maxilar mais bem definido e ganho de volume na região média da face com melhora da aparência do perfil, devido à redução da flacidez da pele sob o queixo. O 3D-SQ apresentou ganho de volume de 1,17 ml à direita e 1,59 ml à esquerda, devido ao reposicionamento do tecido mole. Além disso, foi relatada diminuição do volume das áreas do sulco mentual (0,27 ml à direita e 0,41ml à esquerda), compatível com o ganho de volume acima citado. As medidas considerando os pontos cefalométricos mostraram uma diminuição da altura facial total (distância dos pontos Triquion ao Mentual), sugerindo um deslocamento superior dos tecidos moles. Em conclusão, este relato de caso mostrou resultados quantitativos que podem evidenciar o papel da BoNT-A em procedimentos de lifting facial. Esses resultados reforçam a importância da 3D-SQ para avaliar objetivamente os resultados de harmonização orofacial com BoNT-A e outros materiais. (AU)

Efficacy and Safety of Botulinum Toxin Type A on Persistent Myofascial Pain: A Randomized Clinical Trial.

This study assessed the safety and efficacy of three different doses of BoNT-A for persistent myofascial pain (MFP). One hundred female subjects were randomly assigned into five groups (n = 20): oral appliance (OA), saline solution (SS) and three BoNT-A groups with different doses. Pain intensity and pressure pain threshold were evaluated up to 24 weeks after treatment. Adverse effects related to muscle contraction, masticatory performance, muscle thickness and mandibular bone volume were also assessed. Changes over time were compared within and between groups. The "nparLD" package and Wilcoxon signed-rank test were used to analyze the data. BoNT-A reduced pain intensity (p < 0.0001) and increased pressure pain threshold (p < 0.0001) for up to 24 weeks compared to the placebo. No differences were found between BoNT-A and OA at the last follow-up. A transient decline in masticatory performance (p < 0.05) and muscle contraction (p < 0.0001), and a decrease in muscle thickness (p < 0.05) and coronoid and condylar process bone volume (p < 0.05) were found as dose-related adverse effects of BoNT-A. Regardless of the dose, BoNT-A was as effective as OA on MFP. Notwithstanding, due to BoNT-A dose-related adverse effects, we suggest the use of low doses of BoNT-A in MFP patients that do not benefit from conservative treatments.

Evaluation of pain intensity of the masticatory muscles after occlusal appliance and combined therapy: a 6-months follow-up pilot study

Masticatory muscle pain (MMP) is a common type of orofacial pain.Occlusal appliance (OA) is contemplated as a first-line conservative approach for chronic MMP, however, integrated biopsychosocial approaches such as counseling and self-care therapies (CSG) are also considered essential. Aim: This pilot study aimed to compare the use of a combined therapy (GSG + OA) and solely OA treatment on pain intensity related to chronic MMP over a 6-month follow-up. Methods:For this, 20 patients diagnosed with chronic MMP using the Diagnostic criteria for temporomandibular disorders (DC/TMD) were divided into 2 groups (n=10) and treated with OA or combined therapy (CoT; OA + CSG). Electromyographic muscle activity (EMG), visual analogue scale (VAS) and pressure pain threshold (PPT) were recorded at baseline, 1, 3 and 6 months after treatment. Data was collected and statistical analysis were applied at a significance level of 5%. Results:Results showed no significant differences at baseline among groups for any assessment. VAS showed that both treatments decreased subjective pain in volunteers over time, but no significant differences among both groups were observed at any evaluation time. For electromyography, CoT and OA presented no significant differences throughout the experiment neither on relaxed muscle position or maximum volunteer contraction. Finally, a significantly higher PPT for CoT was found for all muscles at the last assessment point (p<0.05). Conclusion: These findings suggest that both treatments are effective for the reduction of pain perception (VAS) in patients with chronic MMP. However, the addition of CSG to an OA therapy may be more beneficial for the improvement of tenderness on the same patients, at least in a long-term basis (> 3 months). Notwithstanding, a larger study should be performed to substantiate these findings

Association between mandibular advancement device therapy and reduction of excessive daytime sleepiness due to obstructive sleep apnoea.

BACKGROUND: Excessive daytime sleepiness (EDS) is frequently reported as a symptom for obstructive sleep apnoea (OSA), leading to problems with concentration, mood and memory. Mandibular advance device (MAD) is considered as an effective therapy to control OSA, reducing EDS and improving sleep quality. OBJECTIVES: The present study aimed to investigate the effects MAD therapy on EDS of patients diagnosed with OSA. METHODS: Ten patients from the Sleep Medicine Service of the "Hospital Geral Sanatório" (Maceió, Alagoas, Brazil) were diagnosed with EDS, and a personalised MAD was made for each one of them. Nocturnal polysomnography (NPSG) and maintenance of wakefulness test (MWT) were applied before (baseline) and 3 months after the continuous use of the MAD. The number of arousals and micro-arousals at baseline and after treatment was also evaluated. RESULTS: All 10 patients completed the investigation. A significant decrease in the number of arousals and micro-arousals per night of sleep was observed after the use of MAD for three consecutive months (P = 0.0078; Wilcoxon signed-rank test). Also, there was a significant reduction on the apnoea/hypopnea index between baseline and post-treatment values (P = 0.0001; paired t test), as well as an increase in the mean latency for the onset of sleep (MSL) in the MTW (P = 0.0047; paired t test), indicating a significant difference among baseline and after treatment. CONCLUSION: We conclude that the improvement on EDS is associated with the used of MAD in patients diagnosed with OSA, improving their quality of sleep.

Association between mandibular advancement device therapy and reduction of Excessive Daytime Sleepiness due to Obstructive Sleep Apnea.

BACKGROUND: Excessive daytime sleepiness is frequently reported as a symptom for OSA, leading to problems with concentration, mood and memory. MAD are considered as an effective therapy to control OSA, reducing EDS and improving sleep quality. OBJECTIVES: The present study aimed to investigate the effects of mandibular advance device (MAD) therapy on excessive daytime sleepiness (EDS) of patients diagnosed with obstructive sleep apnea (OSA). METHODS: Ten patients from the Sleep Medicine Service of the "Hospital Geral Sanatório" (Maceió, Alagoas, Brazil) were diagnosed with EDS, and a personalized MAD was made for each one of them. Nocturnal polysomnography (NPSG) and Maintenance of wakefulness test (MWT) were applied before (baseline) and three months after the continuous use of the MAD. The number of arousals and microarousals at baseline and after treatment were also evaluated. RESULTS: All 10 patients completed the investigation. A significant decrease in the number of arousals and microarousals per night of sleep was observed after the use of MAD for three consecutive months (P=0.0078; Wilcoxon signed-ranks test). Also, there was a significant reduction on the apnea/hypopnea index between baseline and post-treatment values (P=0.0001; paired-t test), as well as an increase in the mean latency for the onset of sleep (MSL) in the MTW (P=0.0047; paired t- test), indicating a significant difference among baseline and after treatment. CONCLUSION: We conclude that the improvement on EDS is associated with the used of MAD in patients diagnosed with OSA, improving their quality of sleep. This article is protected by copyright. All rights reserved.

Prevalence of psychosocial impairment in temporomandibular disorder patients: A systematic review.

BACKGROUND: Several studies have described high levels of psychosocial disorders in patients with temporomandibular disorders (TMD), but an estimate of their prevalence in populations of TMD patients has never been assessed systematically. OBJECTIVE: To conduct a systematic review of the literature on the prevalence of research diagnostic criteria for TMD (RDC/TMD) Axis II findings in TMD patients. METHODS: Search for articles was carried out by two independent researchers to retrieve papers published after 1992. Inclusion was reserved to observational studies with a minimum sample size of 100 individuals, which used RDC/TMD diagnostic protocol. Quality assessment was performed with the adoption of the methodological evaluation of observational research (MORE). RESULTS: A total of 1186 citations were obtained from search strategy, but only 14 filled the inclusion criteria. Included papers reported somatisation, depression and/or pain-related disability prevalence or scores from populations of 12 different countries. A broad range in the prevalence of moderate-to-severe somatisation in patients with TMD was observed, ranging from 28.5% to 76.6%. Similar results were found for depression, with moderate-to-severe levels in 21.4%-60.1% of patients. Finally, most patients were rated as grade I or II of the Graded Chronic Pain Scale, whereas high pain-related impairment was present in 2.6% to 24% of the individuals. CONCLUSION: The prevalence of severe-to-moderate somatisation and depression was high in TMD patients, while severe physical impairment was not commonly reported.