High-Density Surface Electromyography Guided Precision Botulinum Neurotoxin Injections to Manage Chronic Pelvic Floor Pain

高密度表面肌电图引导精准肉毒杆菌神经毒素注射治疗慢性盆底疼痛

基本信息

批准号：
10512273
负责人：
Yingchun Zhang
金额：
$ 31.1万
依托单位：
UNIVERSITY OF HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10512273
关键词：
Acetylcholine Adverse effects Alternative Therapies Bontoxilysin Chemicals Chronic Clinical Clinical Trials Crossover Design Data Diagnosis Disease Dose Electromyography Ensure Etiology Feasibility Studies Foundations Functional disorder Future Goals Hyperalgesia Image Impairment Individual Inflammatory Injections Interstitial Cystitis Maps Methods Mission Muscle Muscle Spasticity Muscle relaxants Muscle relaxation phase National Institute of Diabetes and Digestive and Kidney Diseases Neuromuscular Junction Nociceptors Oral Pain Patients Pattern Pelvic Floor Muscle Pelvic Pain Pelvic floor structure Pelvis Phenotype Physical therapy Protocols documentation Quality of life Randomized Randomized Controlled Clinical Trials Relaxation Research Safety Secondary to Severities Sex Behavior Site Skeletal Muscle Surface Techniques Therapeutic Intervention Treatment Cost Treatment Efficacy Treatment outcome Woman chronic pelvic pain density dosage efficacy testing improved in vivo interest nerve supply neuromuscular transmission novel optimal treatments pain relief pain symptom personalized approach recruit research clinical testing response success tool treatment optimization treatment strategy

项目摘要

Abstract Interstitial cystitis/ bladder pain syndrome (IC/BPS) is one of the most debilitating chronic pelvic pain (CPP) conditions that negatively impacts the quality of life and sexual activities in 2.7% to 6.5% of women in the US. Pelvic floor hypertonicity (PFH) is prevalent among patients with CPP, and is present in up to 85% of women with IC/BPS. PFH is a multifactorial problem that involves impaired relaxation of the pelvic musculature due to the activation of nociceptors and release of inflammatory chemicals. Current clinical strategies employ physical therapy interventions to relax the muscle to improve muscle coordination. Alternative therapies that use oral or intra-vaginal muscle relaxants may be suggested when conservative methods fail. Specifically, botulinum neurotoxin (BoNT), has received growing interest in managing pelvic pain secondary to PFH. BoNT inhibits the neuromuscular transmission at neuromuscular junctions, indicated by innervation zones (IZs), by blocking the acetylcholine release, leading to transient muscle relaxation, and the relief of pain symptoms. Despite its potency and safety, BoNT can cause dose-dependent adverse effects and is expensive. Studies have demonstrated that increasing the injection distance by 1 cm from the IZs reduced the effect of BoNT by 46%. It is clinically important to localize in vivo the IZ distributions in the pelvic floor muscles to guide precision BoNT injections for optimal treatment efficacy with reduced treatment cost. Our team has successfully developed a novel high-density surface electromyography (HD-sEMG) technique to 1) reliably and quantitatively assess PFH and 2) accurately image the IZ distributions of hypertonic PFMs, and has 3) successfully demonstrated the significant improvement in treatment outcome of BoNT injection with HD-sEMG vs. without HD-sEMG guidance, in managing muscle spasticity. The goal of this proposal is to develop a personalized, precision BoNT injection approach guided by intra-vaginal HD-sEMG to optimize the treatment outcome in IC/BPS management. This research represents the first effort to quantitatively and objectively study the feasibility of using intra-vaginal HD-sEMG for personalized, precision guided BoNT injections to optimize the diagnosis and treatment of IC/BPS. The proposed technique will serve as an in vivo pelvic floor phenotyping tool that can be used to deliver personalized injection of BoNT to personalized injection sites with personalized doses, which will lead to more effective BoNT treatment with reduced treatment cost (by reducing injection dose). The study will also advance our understanding of the pathophysiology of PFH, and mechanism of BoNT management, and help establishing an advanced standard of objective assessment of PFH and BoNT injections.

抽象的间质性膀胱炎/膀胱疼痛综合征 (IC/BPS) 是最令人衰弱的慢性盆腔疼痛 (CPP) 之一这些状况对美国 2.7% 至 6.5% 的女性的生活质量和性活动产生负面影响。盆底肌张力过高 (PFH) 在 CPP 患者中普遍存在，高达 85% 的女性存在这种情况与 IC/BPS。 PFH 是一个多因素问题，涉及骨盆肌肉组织松弛受损，这是由于激活伤害感受器并释放炎症化学物质。目前的临床策略采用物理治疗干预措施可以放松肌肉，改善肌肉协调性。替代疗法当保守方法失败时，可能建议使用口服或阴道内肌肉松弛剂。具体来说，肉毒杆菌神经毒素 (BoNT) 在治疗 PFH 继发的盆腔疼痛方面越来越受到关注。肉毒毒素抑制神经肌肉接头处的神经肌肉传递，由神经支配区 (IZ) 表示，通过阻断乙酰胆碱的释放，导致短暂的肌肉松弛，并缓解疼痛症状。尽管 BoNT 具有效力和安全性，但它可能会引起剂量依赖性的不良反应，而且价格昂贵。研究已经证明，将 IZ 的注射距离增加 1 cm 会降低 BoNT 的效果 46%。在体内定位盆底肌肉中的 IZ 分布以指导精确度在临床上非常重要 BoNT 注射可实现最佳治疗效果并降低治疗成本。我们的团队成功开发了一种新型高密度表面肌电图（HD-sEMG）技术 1) 可靠且定量地评估 PFH，2) 准确地对高渗 PFM 的 IZ 分布进行成像， 3）成功证明了BoNT注射治疗效果的显着改善使用 HD-sEMG 与不使用 HD-sEMG 指导在控制肌肉痉挛方面的比较。该提案的目标是开发一种由阴道内 HD-SEMG 引导的个性化、精准 BoNT 注射方法，以优化 IC/BPS 管理中的治疗结果。这项研究代表了定量和客观研究使用阴道内 HD-sEMG 进行个性化、精确引导 BoNT 的可行性注射以优化 IC/BPS 的诊断和治疗。所提出的技术将作为体内盆底表型分析工具，可用于为个性化患者提供个性化的 BoNT 注射具有个性化剂量的注射部位，这将导致更有效的 BoNT 治疗，并减少治疗费用（通过减少注射剂量）。这项研究还将加深我们对 PFH的病理生理学和BoNT管理机制，并帮助建立先进的标准 PFH 和 BoNT 注射的客观评估。