Botulinum Neurotoxin Type A Research Articles

Application of botulinum toxin A in tissue repair and regeneration

Tissue repair and regeneration present significant clinical challenges. Despite the array of treatments currently available in this domain, the urgent demand for innovative therapies persists, with the goal of enhancing patient quality of life. Recently, the application of botulinum neurotoxin type A (BoNT/A) has expanded within the realm of tissue repair and regeneration. This review critically examines the utilization of BoNT/A, specifically focusing on its vascular effects, potential in nerve regeneration, and contributions to bone healing. This analysis not only offers fresh insights into the diverse mechanisms of action of BoNT/A but also explores additional therapeutic possibilities for patients.

Impact of botulinum toxin type A on tooth movement and bone remodeling in male Wistar rats

ObjectiveWe evaluated whether the use of botulinum neurotoxin type A (BTX-A) in masticatory muscles influences tooth movement and bone remodeling. DesignSeventy-seven male Wistar rats were allocated to the groups: S - Saline (n=20); SM - Saline with movement (n=20); BT - Botulinum toxin (n=18); BTM - Botulinum toxin with movement (n=19). On day 1, 0.02mL of sterile 0.9% saline was administered to groups S and SM and BTX-A (1U in 0.02mL of saline) to groups BT and BTM, in the masseter and temporal muscles laterally. On day 30, a nickel titanium spring was installed to move the first maxillary molar and euthanasia was performed on days 32 and 51. Tooth displacement, maxillary and mandibular bone volumes, collagen neoformation, bone and root resorptions, and masseter morphometry were assessed. Statistical analysis was conducted (p < 0.05). ResultsA higher percentage of type I collagen was observed in the BT than in the S group on day 51 and lower mass, length, and diameter of the masseter fibers in BT and BTM (p < 0.05). Tooth displacement, bone volume, bone and root resorptions, hyaline area, and masseter height showed no difference among groups with and without BTX-A, regardless of tooth movement (p > 0.05). ConclusionsBTX-A did not interfere with tooth displacement, bone volume, and dental and periodontal tissues related to tooth movement in rats; it increased mature collagen in animals without tooth movement; and it caused a decrease in the mass, length, and diameter of the masseter fibers.

Pelvic floor muscle electrical coupling in chronic pelvic pain: Insights into pathophysiology and botulinum toxin treatment effects

This study aimed to assess the electrical coupling between both pelvic floor muscle (PFM) sides (two-sided coupling) and within individual PFM sides (one-sided coupling) in chronic pelvic pain (CPP) before and after botulinum neurotoxin type A (BoNT/A) treatment. Surface electromyographic (sEMG) signals were recorded from the left and right PFM of 24 patients (P) with CPP before and after being treated with BoNT/A (Weeks 0,8,12,24). Recordings were also made in 24 healthy women (H). PFM two-sided and one-sided coupling was evaluated during contractions by the cross-correlation (CC) and the imaginary part of coherency (iCOH) of their sEMG signals. Significant differences between their values were assessed comparing P(0) vs. P(8,12,24) and H vs. P(0,8,12,24). This study showed that PFM two-sided coupling is similar across groups before treatment, while PFM one-sided coupling on the patients’ most painful side is deranged before and also after BoNT/A treatment: amplitude coupling is lower (<CC) and phase difference is greater (>iCOH) than healthy women’s. This could be justified by altered neuromotor control strategies developed as an adaptation to muscle pain, structural and electrical changes in PFM, and alterations in their innervation pattern, which may influence the onset, perpetuation, or recurrence of CPP after treatment.

Botulinum Neurotoxin Type A in paediatric non-neurogenic therapy resistant overactive bladder: a cohort study.

Intradetrusor Botulinum Neurotoxin Type A (BoNT-A) is an increasingly applied treatment modality for overactive bladder (OAB) in children with refractory urinary incontinence. Despite that, evidence is sparse, and the potential not fully understood. The aim of this study was to evaluate the effectiveness and safety of intradetrusor injection in children with refractory functional OAB and urinary incontinence. Furthermore, we aimed to identify predictors of efficacy and side effects to BoNT-A treatment. We conducted a cohort study of children with OAB and urinary incontinence who received intradetrusor injection of BoNT-A in the period 01.01.2016 to 31.12.2020 at our centre. All patients were refractory to standard urotherapy, anticholinergics, mirabegron and the combination of these treatments. Patients with neurogenic bladder were excluded. Primary endpoint was the reduction on the frequency of urinary incontinence episodes from baseline. Secondary endpoints included urodynamic parameters and uroflowmetry characteristics as well as side effects. Forty-three children (mean age at first treatment 10.7 ± 1.8, 30 males) were included. After first treatment, a reduction of ≥ 50% in incontinence episodes was seen in 58% of patients with daytime urinary incontinence (DUI) and 47% of patients with nocturnal enuresis (NE). Adverse events, mainly urinary tract infections (UTI), were reported by 16% of patients after first treatment. Our analysis identified normal cystometric compliance as a significant predictor of treatment effect We estimated the mean duration of effect to be approximately 7months. Intradetrusor BoNT-A injection appears to be a safe and effective option in treating refractory urinary incontinent children with overactive bladder. We identified cystometric compliance as a predictor of response. Most children necessitate repeated treatments. Further prospective and controlled studies are necessary in order to fully identify predictors and potential of treatment.

Association analysis of ADRB3:rs4994 with urodynamic outcome, six months after a single intra-detrusor injection of botulinum toxin, in women with overactive bladder.

Intra-detrusor injection of botulinum neurotoxin type A (BoNT/A) is recommended as a possible treatment for patients with overactive bladder (OAB) in whom first-line therapies have failed. The c.190T > C (rs4994) polymorphism in the gene encoding the beta-3 adrenergic receptor (ADRB3) has been suggested to be associated with predisposition to OAB or with response to OAB treatment via a cholinergic muscarinic receptor antagonist. This prospective study aimed to use a urodynamic parameter-based assessment of response, six months after a single intra-detrusor injection of BoNT/A in female OAB patients, to elucidate possible association with the ADRB3 polymorphism. The study group consisted of 138 consecutive, Polish, adult, female OAB patients. Urodynamic parameters were recorded before injection of BoNT/A and at six months after administration. ADRB3:rs4994 variants were identified by the sequencing of genomic DNA extracted from buccal swabs. Apart from baseline, and relative, increase in Maximum Cystometric Capacity (MCC) six months after BoNT/A injection, no significant differences were found in urodynamic parameters between reference TT homozygotes and women with at least one C allele. Our results do not exclude that ADRB3:rs4994 variants are associated with a positive urodynamic test-based response to intra-detrusor injection of BoNT/A in females with OAB.

Delphi Analysis: Optimizing Anatomy Teaching and Ultrasound Training for Botulinum Neurotoxin Type A Injection in Spasticity and Dystonia.

Our objective was to provide expert consensus on best practices for anatomy teaching and training on ultrasound-guided botulinum neurotoxin type A (BoNT-A) injection for specialists involved in treating spasticity and dystonia. Nine experts (three neurologists; six physical medicine and rehabilitation physicians) participated in a three-round modified Delphi process. Over three rounds, experts reached consensus on 15 of 16 statements describing best practices for anatomy and BoNT-A injection training. They unanimously agreed that knowledge of the target audience, including their needs and current competency, is crucial when designing training programs. Experts also agreed that alignment between instructors is essential to ensure consistency of approach over time and between regions, and that training programs should be simple, adaptable, and "hands-on" to enhance engagement and learning. Consensus was also reached for several other key areas of training program development. The best-practice principles identified by expert consensus could aid in the development of effective, standardized programs for anatomy teaching and BoNT-A injection training for the purposes of treating spasticity and dystonia. This will enhance the exchange of knowledge, skills, and educational approaches between global experts, allowing more specialists to treat important movement disorders and ultimately improving patient outcomes.

Model-based interspecies interpretation of botulinum neurotoxin type A on muscle-contraction inhibition.

Botulinum neurotoxins (BoNTs) are commonly used in therapeutic and cosmetic applications. One such neurotoxin, BoNT type A (BoNT/A), has been studied widely for its effects on muscle function and contraction. Despite the importance of BoNT/A products, determining the blood concentrations of these toxins can be challenging. To address this, researchers have focused on pharmacodynamic (PD) markers, including compound muscle action potential (CMAP) and digit abduction scoring (DAS). In this study, we aimed to develop a probabilistic kinetic-pharmacodynamic (K-PD) model to interpret CMAP and DAS data obtained from mice and rats during the development of BoNT/A products. The researchers also wanted to gain a better understanding of how the estimated parameters from the model relate to the bridging of animal models to human responses. We used female Institute of Cancer Research mice and Sprague-Dawley (SD) rats to measure CMAP and DAS levels over 32weeks after administering BoNT/A. We developed a muscle-contraction inhibition model using a virtual pharmacokinetic (PK) compartment combined with an indirect response model and performed model diagnostics using goodness-of-fit analysis, visual predictive checks (VPC), and bootstrap analysis. The CMAP and DAS profiles were dose-dependent, with recovery times varying depending on the administered dose. The final K-PD model effectively characterized the data and provided insights into species-specific differences in the PK and PD parameters. Overall, this study demonstrated the utility of PK-PD modeling in understanding the effects of BoNT/A and provides a foundation for future research on other BoNT/A products.

RimabotulinumtoxinB: An Update.

Botulinum type-A toxin is a well established aesthetic and medical treatment. While the usage of type-B toxin is less common, there is a growing interest in using type-B toxin, especially in those who are treatment resistant. To evaluate the primary FDA-approved clinical applications of rimabotulinumtoxinB, along with established and emerging off-label clinical indications. Articles were reviewed from PubMed database and Food and Drug Adminstration guidelines. Facial rhytids tend to use a higher conversion ratio between type A and type B toxin, due to type B toxin's weaker affinity to muscles and higher affinity for sweat glands. Specially, a 1:100 to 1:50 ratio was utilized for glabellar rhytids, a 1:25 to 1:50 ratio for periocular rhytids, a 1:50 to 1:66.6 ratio for cervical dystonia, a 1:20 to 1:50 ratio for hyperhidrosis, and a 1:25 to 30 ratio for sialorrhea. Type B toxin has demonstrated its safety and efficacy in treating facial rhytids, cervical dystonia, sialorrhea and hyperhidrosis, with potential for novel applications under investigation. Regardless of injection location and clinical applications, dry mouth and dysphagia remained the most common side effects. Across all indications, type B toxin appeared to have a faster onset of action, a dose-dependent clinical duration, and a dose-dependent adverse effect profile.

Rare and novel complications of botulinum neurotoxin type A and dermal filler injections

Botulinum neurotoxin type A (BoNTA) and filler injection procedures usually provide predicted outcomes with a low incidence of complications. Most of the complications after these procedures have been extensively discussed. In this study, we report on these injectables’ less well-known, recently reported, and novel complications and attempt to clarify the underlying mechanisms. Counterfeit or mishandled BoNTA has been associated with botulism. BoNTA has been linked to uncommon complications, including morphea-like lesions, nontuberculous mycobacterial infections, vascular occlusion, and pseudoaneurysm of the superficial temporal artery. Unusual complications from filler injection include nonscarring alopecia, intraoral necrosis, nontuberculous mycobacterial infections, xanthelasma-like reactions, intracranial perforation, and pneumosinus dilatans. Post-BoNTA injection nodules and filler infection from bone destruction due to cocaine use are new complications. These complications pose a challenge for diagnosis and treatment. This publication aims to assist in promptly identifying and managing these rare and novel complications when necessary.

Comprehensive Observational and Longitudinal study on the Outbreak of Stroke-related Spasticity focusing on the Early Onset management with Botulinum NeuroToxin (COLOSSEO-BoNT): protocol for a real-world prospective observational study on upper limb spasticity

IntroductionPoststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its...

Assessing muscle architecture with ultrasound: implications for spasticity.

Botulinum Neurotoxin Type A (BoNT-A) injections using Ultrasound (US) guidance have led to research evaluating changes in muscle architecture. Controversy remains as to what constitutes increased Echo-Intensity (EI) in spastic muscles and whether this may affect outcomes. We aim to provide a narrative review of US muscle architecture changes following Central Nervous System (CNS) lesions and explore their relationship to spasticity. Medline, CINAHL, and Embase databases were searched with keywords: ultrasonography, hypertonia, spasticity, fibrosis, and Heckmatt. Three physicians reviewed the results of the search to select relevant papers. Reviews identified in the search were used as a resource to identify additional studies. A total of 68 papers were included. Four themes were identified, including histopathological changes in spastic muscle, effects of BoNT-A on the muscle structure, available US modalities to assess the muscle, and utility of US assessment in clinical spasticity. Histopathological studies revealed atrophic and fibro-fatty changes after CNS lesions. Several papers described BoNT-A injections contributing to those modifications. These changes translated to increased EI. The exact significance of increased muscle EI remains unclear. The Modified Heckmatt Scale (MHS) is a validated tool for grading muscle EI in spasticity. The use of the US may be an important tool to assess muscle architecture changes in spasticity and improve spasticity management. Treatment algorithms may be developed based on the degree of EI. Further research is needed to determine the incidence and impact of these EI changes in spastic muscles.

Ready-to-use abobotulinumtoxinA solution versus powder botulinumtoxinA for treatment of glabellar lines: Investigators' and subjects' experience in a Phase IV study.

Botulinum neurotoxin type A (BoNT-A) is well-established for treatment of glabellar lines (GLs), and mostly formulated as powders requiring reconstitution for injection. The approved liquid formulation, ready-to-use (RTU) abobotulinumtoxinA was developed to ease injection procedures and prevent reconstitution errors. This multicenter, open-label, Phase IV study evaluated GL treatment experience using RTU abobotulinumtoxinA versus powder BoNT-A (onabotulinumtoxinA). Females with experience of BoNT-A facial treatment were randomized 2:1 to GL treatment with 50 U RTU abobotulinumtoxinA (N = 99) or 20 U powder BoNT-A (N = 51) and followed-up for 6 months or 1 month, respectively. Assessments included: time to prepare each product for injection (primary endpoint); investigators' experience with product preparation/reconstitution; investigators' and subjects' treatment experience; safety; and for the RTU product: aesthetic improvement of GLs; subject satisfaction. Compared with powder BoNT-A, RTU abobotulinumtoxinA required statistically significantly less preparation time (mean 0:33 vs. 1:34 min: s; p < 0.0001). Investigators preferred RTU abobotulinumtoxinA over powder BoNT-A (81% of treatment sessions) and found it allowed more time to communicate with subjects (97%). All investigators (100%) also found it easy-to-use, easy-to-learn, and that it fulfilled their expectations. Subjects found the RTU abobotulinumtoxinA treatment comfortable (91%), and through 6 months posttreatment, most reported satisfaction with their appearance (≥88%), looking natural (≥95%) and refreshed (≥80%). At Month 1, 99% of RTU-treated subjects had investigator-assessed improved aesthetic appearance in GLs, maintained in 76% at Month 6. No serious adverse events occurred. RTU abobotulinumtoxinA for GL treatment is well-tolerated, efficacious, shows high levels of subject satisfaction throughout 6 months, saves time, and is preferred by clinicians over powder BoNT-A. NCT05277337.

Delphi Analysis: Anatomy and Botulinum Neurotoxin Type-A (BoNT-A) Injection Training for Spasticity and Dystonia

Delphi Analysis: Anatomy and Botulinum Neurotoxin Type-A (BoNT-A) Injection Training for Spasticity and Dystonia

Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain.

Neuropathic pain (NPP) remains a clinically challenging condition, driven by the activation of spinal astrocytes and the complex release of inflammatory mediators. This study aimed to examine the roles of Rab8a and SNARE complex proteins in activated astrocytes to uncover the underlying mechanisms of NPP. The research was conducted using a rat model with chronic constriction injury (CCI) of the sciatic nerve and primary astrocytes treated with lipopolysaccharide. Enhanced expression of Rab8a was noted specifically in spinal dorsal horn astrocytes through immunofluorescence. Electron microscopy observations showed increased vesicular transport and exocytic activity in activated astrocytes, which was corroborated by elevated levels of inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α detected through quantitative PCR. Western blot analyses confirmed significant upregulation of Rab8a, VAMP2, and Syntaxin16 in these cells. Furthermore, the application of botulinum neurotoxin type A (BONT/A) reduced the levels of vesicle transport-associated proteins, inhibiting vesicular transport in activated astrocytes. These findings suggest that the Rab8a/SNARE pathway in astrocytes enhances vesicle transport and anchoring, increasing the secretion of bioactive molecules that may play a crucial role in the pathophysiology of NPP. Inhibiting this pathway with BONT/A offers a novel therapeutic target for managing NPP, highlighting its potential utility in clinical interventions.

The Usefulness of Salivary Gland Organoids for Evaluation of the Potency of Botulinum Neurotoxin.

Botulinum neurotoxin (BoNT) is a substance used to treat chronic sialorrhea, muscle dystonia, and is used in cosmetic applications. Measuring the potency of BoNT is crucial because it acts even with a small amount. However, the current methods for measuring the potency of BoNT involve using two-dimensional neuroblastoma cell line-based methods. In this study, we aimed to develop a new method to measure the potency of BoNT using a three-dimensional organoid culture system. We established the optimal conditions for coculturing N2a neuronal cells with murine salivary gland organoids (SGOs). After determining the appropriate chemical concentrations, we treated the SGOs cocultured with N2a cells with BoNT type A (BoNT/A). We confirmed the expression of salivary gland-related genes and proteins using real-time polymerase chain reaction (PCR) and immunofluorescence staining. The SGOs cocultured with N2a cells showed that the dendrites or axons of neuronal cells were in contact with the outermost layer of the SGOs. When we applied acetylcholine and neostigmine to the coculture systems, the mRNA expression of Aqp5 and Bhlha15, associated with salivary gland secretory cells, increased. However, this effect was reversed when BoNT/A was applied, as confirmed through real-time PCR. We found that the coculture system of SGOs and N2a neuronal cells can potentially serve as a potency testing platform for BoNT. NA Laryngoscope, 134:2697-2704, 2024.

Development of plug-and-deliverable intracellular protein delivery platforms based on botulinum neurotoxin

Intracellular protein delivery systems have great potential in the fields of therapeutics development and biomedical research. However, targeted delivery, passing through the cell membrane without damaging the cells, and escaping from endosomal entrapment of endocytosed molecular cargos are major challenges of the system. Here, we present a novel intracellular protein delivery system based on modularly engineered botulinum neurotoxin type A (BoNT/A). LHNA domain, consisting of light chain and endosomal escape machinery of BoNT/A, was genetically fused with SpyCatcher (SC) and EGFR targeting affibody (EGFRAfb) to create SC-LHNA-EGFRAfb, a target-specific and protein cargo-switchable BoNT/A-based intracellular protein delivery platform. SC-LHNA-EGFRAfb was purely purified in large quantities, efficiently ligated with multiple ST-fused protein cargos individually, generating a variety of protein cargo-containing intracellular delivery complexes, and successfully delivered ligated protein cargos into the cytosol of target cells via receptor-mediated endocytosis, followed by endosomal escape and subsequent cytosolic delivery. SC-LHNA-EGFRAfb enhanced intracellular delivery efficiency of protein toxin, gelonin, by approximately 100-fold, highlighting the crucial roles of EGFRAfb and LHNA domain as a targeting ligand and an endosomal escape machinery, respectively, in the delivery process. The BoNT-based plug-and-deliverable intracellular protein delivery system has the potential to expand its applications in protein therapeutics and manipulating cellular processes.

A sensitive cell-based assay for testing potency of botulinum neurotoxin type A

Botulinum neurotoxin type A (BoNT/A) is a biopharmaceutic widely used for the treatment of neu­rological diseases and in aesthetic medicine to achieve months-long paralysis of target muscles and glands. Large numbers of mice are used in the mouse bioassay (MBA) for various botulinum-related applications including batch release potency testing, antitoxin testing, countermeasure development, and basic research. BoNT/A intoxication causes severe suffering to the mice used for testing, and application-specific, non-animal alternatives are urgently needed. Cell-based assays (CBA) need to replicate all the physiological steps of botulinum intoxication, comprising neuronal binding, internali­zation, endosomal escape, and cleavage of synaptosomal-associated protein of 25 kDa (SNAP25). However, the CBA currently in use have limitations. In this study we show that LAN5 cells, a human neuroblastoma-derived cell line, are sensitive to BoNT/A and can be engineered to express a recom­binant NanoLuciferase (NanoLuc)-tagged SNAP25 reporter molecule. On exposure, the reporter molecule is cleaved and releases a NanoLuc-SNAP25 fragment that can be captured on a 96-well plate for quantitative luminometry using a cleavage-specific SNAP25 antibody. We demonstrate, using purified BoNT/A and a commercial BoNT/A product, that the sensitivity of this new cell-based assay is in the fM range, comparable to that of the MBA. The new assay could replace the MBA in research and commercial testing of BoNT/A, benefiting both scientific progress and animal welfare.

Machine learning powered detection of biological toxins in association with confined lateral flow immunoassay (c-LFA).

Biological weapons, primarily dispersed as aerosols, can spread not only to the targeted area but also to adjacent regions following the movement of air driven by wind. Thus, there is a growing demand for toxin analysis because biological weapons are among the most influential and destructive. Specifically, such a technique should be hand-held, rapid, and easy to use because current methods require more time and well-trained personnel. Our study demonstrates the use of a novel lateral flow immunoassay, which has a confined structure like a double barbell in the detection area (so called c-LFA) for toxin detection such as staphylococcal enterotoxin B (SEB), ricinus communis (Ricin), and botulinum neurotoxin type A (BoNT-A). Additionally, we have explored the integration of machine learning (ML), specifically, a toxin chip boosting (TOCBoost) hybrid algorithm for improved sensitivity and specificity. Consequently, the ML powered c-LFA concurrently categorized three biological toxin types with an average accuracy as high as 95.5%. To our knowledge, the sensor proposed in this study is the first attempt to utilize ML for the assessment of toxins. The advent of the c-LFA orchestrated a paradigm shift by furnishing a versatile and robust platform for the rapid, on-site detection of various toxins, including SEB, Ricin, and BoNT-A. Our platform enables accessible and on-site toxin monitoring for non-experts and can potentially be applied to biosecurity.

New approach to generating of human monoclonal antibodies specific to the proteolytic domain of botulinum neurotoxin A.

Botulinum neurotoxins (BoNTs) cause botulism and are the most potent natural toxins known. Immunotherapy with neutralizing monoclonal antibodies (MAbs) is considered to be the most effective immediate response to BoNT exposure. Hybridoma technology remains the preferred method for producing MAbs with naturally paired immunoglobulin genes and with preserved innate functions of immune cells. The affinity-matured human antibody repertoire may be ideal as a source for antibody therapeutics against BoNTs. In an effort to develop novel BoNT type A (BoNT/A) immunotherapeutics, sorted by flow cytometry plasmablasts and activated memory B cells from a donor repeatedly injected with BoNT/A for aesthetic botulinum therapy could be used due to obtain hybridomas producing native antibodies. Plasmablasts and activated memory B-cells were isolated from whole blood collected 7 days after BoNT/A injection and sorted by flow cytometry. The sorted cells were then electrofused with the K6H6/B5 cell line, resulting in a producer of native human monoclonal antibodies (huMAbs). The 3 antibodies obtained were then purified by affinity chromatography, analyzed for binding by Western blot assay and neutralization by FRET assay. We have succeeded in creating 3 hybridomas that secrete huMAbs specific to native BoNT/A and the proteolytic domain (LC) of BoNT/A. The 1B9 antibody also directly inhibited BoNT/A catalytic activity in vitro. The use activated plasmablasts and memory B-cells isolated at the peak of the immune response (at day 7 of immunogenesis) that have not yet completed the terminal stage of differentiation but have undergone somatic hypermutation for hybridization allows us to obtain specific huMAbs even when the immune response of the donor is weak (with low levels of specific antibodies and specific B-cells in blood). A BoNT/A LC-specific antibody is capable of effectively inhibiting BoNT/A by mechanisms not previously associated with antibodies that neutralize BoNT. Antibodies specific to BoNT LC can be valuable components of a mixture of antibodies against BoNT exposure.

Treatment with botulinum toxin of masseter hypertrophy, myalgia of the tendons and attrition induced by bruxism

Bruxism is a disabling condition in which unconscious contractions of the masticulatory muscles lead to teeth grinding and jaw clenching. Symptoms include toothache, temporomandibular dysfunction, headache and attrition. Treatment options range from conservative approaches to invasive interventions. Education, stress reduction, avoidance of stimulants, and relaxation techniques can help in mild cases. Wearing an occlusal splint can reduce attrition. Botulinum neurotoxin type A (BoNT-A) injections are a treatment option temporarily causing partial paralysis of the masticulatory muscles. BoNT-A is a treatment for reducing symptoms and improving the quality of life of patients with bruxism that has been proven safe and effective. The effects usually last several months. To achieve the best results and minimize side effects, BoNT-A injections should be applied by an experienced practitioner.