Botulinum toxin in muscles of mastication

咀嚼肌中的肉毒杆菌毒素

• 批准号: 7583606
• 负责人: SUSAN W HERRING
• 金额: $ 36.13万
• 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/7583606
• 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; Cholinergic Agents; Classification; Clinical; Clinical Treatment; Condition; Contracture; Cosmetics; Data; Dental Implants; Electromyography; Face; Family suidae; Fibroblasts; Fibrosis; Fracture; Future; Goals; Health; Histology; Human; Individual; Injection of therapeutic agent; Intramuscular; Invasive; 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; Numbers; Oryctolagus cuniculus; Outcome; Pain; Paralysed; Patients; Pattern; Pharmaceutical Preparations; Physiological; Population; Provider; Pterygoid Muscle; Public Health; Recovery; Recovery of Function; Reporting; Research; Rest; Series; Side; Skeleton; Sus scrofa; System; Techniques; Temporomandibular Joint; Testing; Time; Toxin; Validation; alveolar bone; base; bone; bone loss; cholinergic; craniofacial; human study; nerve supply; neuron loss; 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（BoNT/A）是一种强效麻痹剂，广泛用于治疗咬肌。临床报告表明，BoNT/A 治疗的某些影响（萎缩、电活动减少）对下颌肌肉的影响异常持久，但其原因尚不清楚。可能的解释是运动单位数量减少或卫星细胞群反应不佳，但迄今为止尚未进行动物研究来研究毒素治疗后下颌肌肉的生物学。在临床使用中，咬合力比咬肌恢复得更快，但其机制尚不清楚。此外，BoNT/A 声称的一项但未经证实的好处是，肌肉麻痹后下颌将减轻负荷。如果是这样，那么就会导致废用性骨质流失，但这也没有得到证实。拟议的研究是使用两种公认的人类咀嚼功能动物模型（兔子和猪）系统检查 BoNT/A 对咬肌和下颌骨的影响。具体目标 1 将使用肌电图和运动分析来阐明肌肉使用的代偿模式是否可以解释咬合力和咀嚼能力的早期恢复。具体目标 2 将通过应变计记录和骨结构的 microCT 检查来评估注射侧下颌骨可能的卸载。据推测，咬肌麻痹后，无负荷区域的骨量会迅速减少。具体目标 3 将研究 BoNT/A 麻痹是否会导致咬肌内运动单位的重组，并将采用神经追踪和神经刺激技术。对毒素的立即反应预计是扩大通常高度受限的运动单位区域。还将研究运动神经元丢失的可能性。具体目标4将建立肌肉退化和修复的过程，以探索为什么咬肌会长期萎缩。卫星细胞群的活性将通过复制和细胞死亡标记以及跟踪肌球蛋白重链组成的变化来描述。总之，该项目探讨了常见临床治疗的生物学基础。它将提供有关肌肉及其神经如何受到影响、下颌生物力学如何改变以及下颌运动系统的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背景。公共健康相关性：A 型肉毒杆菌神经毒素（其商业名称为 Botox）使肌肉长时间麻痹，在此期间肌肉萎缩，神经重组。成千上万的患者已经接受了这种药物来缩小大下巴的肌肉。拟议的研究将使用动物模型来研究咀嚼系统如何适应毒素以及再生反应的生物学。结果将指导临床医生了解功能后果，并有助于验证治疗的临床原理。