Botulinum toxin in muscles of mastication

咀嚼肌中的肉毒杆菌毒素

• 批准号: 7872827
• 负责人: SUSAN W HERRING
• 金额: $ 37.19万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7872827
• 关键词: Accounting; Address; Affect; Animal Model; Animals; Architecture; Atrophic; Behavior; Biology; Biomechanics; Bite Force; Bontoxilysin; Botox; Botulinum Toxin Type A; Botulinum Toxins; Cell Death; Clinical; Clinical Treatment; Contracture; Cosmetics; Data; Dental Implants; Electromyography; FDA approved; Face; Family suidae; Fibroblasts; Fibrosis; Fracture; Future; Goals; Health; Histology; Human; Individual; Injection of therapeutic agent; Intramuscular; Jaw; Larynx; Learning; Life; Location; Mandible; Masseter Muscle; Mastication; Masticatory muscles; Measures; Medial; Motion; Motor; Motor Neurons; Movement; Muscle; Muscle function; Muscular Atrophy; Myosin Heavy Chains; Names; Natural regeneration; Nerve; Neuronal Plasticity; Oryctolagus cuniculus; Osteopenia; Outcome; Pain; Paralysed; Patients; Pattern; Pharmaceutical Preparations; Physiological; Population; Provider; Pterygoid Muscle; Recovery; Recovery of Function; Reporting; Research; Rest; Series; Side; Skeleton; System; Techniques; Temporomandibular Joint; Testing; Time; Toxin; Validation; alveolar bone; base; bone; bone loss; bone mass; cholinergic; craniofacial; muscle degeneration; muscular system; nerve supply; neuromuscular; neuron loss; orbit muscle; public health relevance; regenerative; repaired; research study; response; satellite cell; success

DESCRIPTION (provided by applicant): Botulinum neurotoxin type A (BoNT/A), a potent paralytic, is a widely used treatment for the masseter muscles. Clinical reports suggest that some effects of BoNT/A treatment (atrophy, reduced electrical activity) are unusually long-lasting in jaw muscles, but the reasons for this are not clear. Possible explanations are reduction in the number of motor units or a poor response of the satellite cell population, but as yet no animal studies have been performed to study the biology of jaw muscles after toxin treatment. In clinical usage, bite force recovers more rapidly than the masseter, but the mechanism for this is unknown. Additionally, one benefit claimed for BoNT/A but unproven is that the jaw will be unloaded after muscle paralysis. If so, then disuse loss of bone should result, but this too is undemonstrated. The proposed research is a systematic examination of the effects of BoNT/A on the masseter muscle and the mandible, using two accepted animal models of human masticatory function, rabbit and pig. Specific Aim 1 will use electromyography and motion analysis to clarify whether compensatory patterns of muscle usage account for the early return of bite force and masticatory ability. Specific Aim 2 will assess the possible unloading of the injection side mandible by strain gage recording and microCT examination of bony architecture. Masseter paralysis is hypothesized to be followed rapidly by loss of bone mass in unloaded regions. Specific Aim 3 will investigate whether BoNT/A paralysis causes reorganization of motor units within the masseter and will employ neurotracing and nerve stimulation techniques. The immediate response to the toxin is expected to be expansion of normally highly restricted motor unit territories. The possibility of motor neuron loss will also be investigated. Specific Aim 4 will establish the course of muscle degeneration and repair to explore why atrophy is long-lasting in the masseter. The activity of the satellite cell population will be described through markers of replication and cell death and by tracking changes in myosin heavy chain composition. In summary, this project addresses the biology underlying a common clinical treatment. It will provide new information on how the muscles and their nerves are affected, how jaw biomechanics are altered, and the extent of neuroplasticity of the jaw motor system. The results will provide an informed background for patient treatment and for interpreting outcomes. PUBLIC HEALTH RELEVANCE: Botulinum neurotoxin type A, better known under the commercial name of Botox, paralyzes muscles for extended periods of time, during which the muscles atrophy and the nerves reorganize. Thousands of patients have received the drug in order to shrink large jaw muscles. The proposed research will use animal models to study how the chewing system adapts to the toxin and the biology of the regenerative response. The results will guide clinicians in understanding functional consequences and help to validate clinical rationales for treatment.

描述（由申请人提供）：A型肉毒杆菌神经毒素A型（BONT/A），一种有效的麻痹，是一种广泛使用的咬肌。临床报道表明，BONT/A治疗的某些影响（萎缩，电活动降低）在下颌肌肉中异常长期持久，但原因尚不清楚。可能的解释是减少运动单位的数量或卫星细胞种群的反应不佳，但尚未进行动物研究来研究毒素治疗后颌骨的生物学。在临床用法中，咬伤力的恢复速度比咬人机更快，但尚不清楚的机制。此外，声称BONT/A但未经证实的一个好处是，下颌将在肌肉麻痹后卸载。如果是这样，则应消除骨骼的损失，但这也是没有证明的。拟议的研究是对BONT/A对咬合肌肉和下颌骨的影响进行系统的检查，使用了两个可接受的人类咀嚼功能，兔和猪的动物模型。特定目标1将使用肌电图和运动分析来阐明肌肉使用的补偿模式是否解释了咬合力和咀嚼能力的早期回归。特定的目标2将通过应变计记录和骨体系结构的Microct检查来评估注射侧的卸载。假设摩托瘫痪迅速在未加载区域中骨骼质量丧失。具体目标3将研究BONT/A瘫痪是否会导致咬合体内运动单位的重组，并采用神经接触和神经刺激技术。对毒素的直接反应预计将是通常受到高度限制的运动单位领土的扩展。运动神经元丧失的可能性也将被研究。特定的目标4将建立肌肉变性和修复的过程，以探讨为什么肥胖症在棒球中持续持久。卫星细胞种群的活性将通过复制和细胞死亡的标记以及跟踪肌球蛋白重链组成的变化来描述。总而言之，该项目涉及常见临床治疗的生物学。它将提供有关肌肉和神经如何影响，下颌生物力学的改变以及下颌运动系统神经可塑性程度的新信息。结果将为患者治疗和解释结果提供知情的背景。公共卫生相关性：A型肉毒杆菌毒素A型，以肉毒杆菌毒素的商业名称为商业名称，瘫痪了肌肉长时间，在此期间，肌肉萎缩和神经重组。成千上万的患者已经接受了这种药物，以收缩大颌骨。拟议的研究将使用动物模型研究咀嚼系统如何适应毒素和再生反应的生物学。结果将指导临床医生理解功能后果，并有助于验证临床理由进行治疗。