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

摘要 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 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的条件。 骨盆底张力亢进（PFH）在CPP患者中普遍存在，并且存在于高达85%的女性中 IC/BPS PFH是一个多因素的问题，涉及骨盆肌肉组织的松弛受损， 伤害感受器的激活和炎症化学物质的释放。目前的临床策略采用 物理治疗干预放松肌肉，以改善肌肉协调。的替代疗法 当保守方法失败时，建议使用口服或阴道内肌肉松弛剂。具体地说， 肉毒杆菌神经毒素（BoNT）在治疗继发于PFH的骨盆疼痛方面受到越来越多的关注。Bont 抑制神经肌肉接头处的神经肌肉传递，由神经支配区（IZs）指示， 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。 尽管它的效力和安全性，BoNT可能会导致剂量依赖性的不良反应，并且价格昂贵。研究 已经证明，从IZ增加1cm的注射距离通过以下方式降低了BoNT的作用： 百分之四十六临床上重要的是在体内定位IZ分布在盆底肌肉，以指导精度 BoNT注射以降低治疗成本获得最佳治疗效果。 我们的团队已经成功地开发了一种新的高密度表面肌电图（HD-sEMG）技术 为了1）可靠和定量地评估PFH和2）准确地成像高渗PFM的IZ分布， 并且3）成功地证明了BoNT注射的治疗结果的显著改善 有HD-sEMG与无HD-sEMG指导的肌肉痉挛管理对比。这项提案的目的是 开发一种由阴道内HD-sEMG指导的个性化、精确的BoNT注射方法， IC/BPS管理的治疗结果。这项研究代表了定量和 客观地研究使用阴道内HD-sEMG进行个性化、精确引导的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一种体内 骨盆底表型分析工具，可用于提供个性化的BoNT注射到个性化的 个性化剂量的注射部位，这将导致更有效的BoNT治疗， 治疗成本（通过减少注射剂量）。这项研究还将促进我们对 PFH的病理生理机制和BoNT的治疗机制，并帮助建立先进的标准 PFH和BoNT注射的客观评估。

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.