Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection

Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months’ duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment.     

Clinical Uses of Botulinum Neurotoxins: Current Indications,Limitations and Future Developments

Botulinum neurotoxins (BoNTs) cause flaccid paralysis by interfering with vesicle fusion and neurotransmitter release in the neuronal cells. BoNTs are the most widely used therapeutic proteins. BoNT/A was approved by the U.S. FDA to treat strabismus, blepharospam, and hemificial spasm as early as 1989 and then for treatment of cervical dystonia, glabellar facial lines, axillary hyperhidrosis, chronic migraine and for cosmetic use. Due to its high efficacy, longevity of action and satisfactory safety profile, it has been used empirically in a variety of ophthalmological, gastrointestinal, urological, orthopedic, dermatological, secretory, and painful disorders. Currently available BoNT therapies are limited to neuronal indications with the requirement of periodic injections resulting in immune-resistance for some indications. Recent understanding of the structure-function relationship of BoNTs prompted the engineering of novel BoNTs to extend therapeutic interventions in non-neuronal systems and to overcome the immune-resistance issue. Much research still needs to be done to improve and extend the medical uses of BoNTs.     

Management of bladder, prostatic and pelvic floor disorders with botulinum neurotoxin

Since its introduction in the late 1970s for the treatment of strabismus and blepharospasm, botulinum toxin (BoNT) has been increasingly used in the interventional treatment of several other disorders characterized by excessive or inappropriate muscle contractions. The use of this pluripotential agent has extended to a plethora of conditions including: focal dystonia; spasticity; inappropriate contraction in most sphincters of the body such as those associated with spasmodic dysphonia, esophageal achalasia, chronic anal fissure, and vaginismus; eye movement disorders; other hyperkinetic disorders including tics and tremors; autonomic disorders such as hyperhidrosis; genitourinary disorders such as overactive and neurogenic bladder, non-bacterial prostatitis and benign prostatic hyperplasia; and aesthetically undesirable hyperfunctional facial lines. In addition, BoNT is being investigated for the control of the pain, and for the management of tension or migraine headaches and myofascial pain syndrome. BoNT injections have several advantages over drugs and surgical therapies in the management of intractable or chronic disease. Systemic pharmacologic effects are rare; permanent destruction of tissue does not occur. Graded degrees of relaxation may be achieved by varying the dose injected; most adverse effects are transient. Finally, patient acceptance is high. In this paper, clinical experience over the last years with BoNT in urological impaired patients will be illustrated. Moreover, this paper presents current data on the use of BoNT to treat pelvic floor disorders.     

分娩方式对盆底自主收缩肌肉力量影响与盆底肌力训练作用的探究

目的探究分娩方式对盆底自主收缩肌肉力量的影响,分析盆底肌力训练的作用。方法选取自然分娩产妇50例为A组;选取剖宫产的产妇50例为B组;抽查未孕妇女50例为C组。对三组妇女的骨盆底肌力评分、15s内肌肉收缩次数、用力收缩持续时间进行对比分析,从而探究分娩方式对盆底自主收缩肌肉力量的影响。之后,从A、B组中各抽取25例组成D组,将A、B组其余妇女组成E组,其中D组妇女进行盆底肌力训练,E组妇女只做常规处理,对D组、E组妇女的骨盆底肌力评分、15s内肌肉收缩次数、用力收缩持续时间进行对比分析,从而分析盆底肌力训练的作用。结果 A组、B组妇女的骨盆底肌力评分、15s肌肉收缩次数、用力收缩持续时间均明显低于C组。B组妇女的骨盆底肌力评分、15s内肌肉收缩次数、用力收缩持续时间均明显低于A组。E组妇女的骨盆底肌力评分、15s内肌肉收缩次数、用力收缩持续时间均明显低于D组。结论剖宫产妇女、自然分娩妇女的骨盆底肌力评分、15s内肌肉收缩次数、用力收缩持续时间低于未孕妇女,剖宫产妇女的骨盆底肌力评分、15s内肌肉收缩次数、用力收缩持续时间低于自然分娩的妇女,盆地肌力训练能够有效地促进盆底自主收缩肌肉力量的恢复。     

盆底康复治疗产后阴道壁脱垂合并细菌性阴道病的临床研究

目的探讨盆底康复治疗（电刺激＋生物反馈治疗）用于产后阴道壁脱垂合并细菌性阴道病患者的临床效果。方法对产妇首先进行盆底肌力初次筛查,采用PHENIX机检测盆底Ⅰ、Ⅱ类纤维的肌力及阴道动态压力。对存在阴道壁脱垂合并细菌性阴道病患者155例按单盲法分为治疗组82例和对照组75例。治疗组根据PHENIXUSB4内置方案（脏器脱垂方案）进行盆底康复治疗5周,对照组进行盆底肌kegel训练5周。两组患者同时进行细菌性阴道病治疗。比较两组临床治疗效果。结果治疗组总有效率93．90％,优于对照组的74．67％（X^2=11．19,P〈0．05）。治疗组Aa点、Ap点值及POP—Q分期降低,阴道壁脱垂情况改善,盆底I类、Ⅱ类肌纤维肌力、阴道动态压力改善,与对照组差异均有统计学意义（均P〈0．05）。结论盆底康复治疗能明显改善产后患者阴道壁脱垂情况,且无损伤,无痛苦,疗效确切,治疗效果不受阴道炎影响,方法简便。     

天津地区产后盆底肌力损伤的相关因素分析

摘要：目的 探讨不同因素对产后盆底肌力损伤的影响,为早期防治盆底功能障碍性疾病（PFD）提供临床依据。方法 选取2011年12月-2014年12月参加天津市产后盆底功能筛查的产妇65 630例,采用统一的检测方法和诊断标准,由各区县妇幼保健机构对辖区内产妇进行盆底肌力测评,分析不同因素对产后盆底肌力的影响。结果 产后发生肌力异常19 452例,异常率为29.6%;其中农村妇女的肌力异常率高于城市妇女（33.9% vs 27.8%）,初中及以下学历的肌力异常率高于中专或高中和大专及以上学历者（34.1% vs 30.4% & 27.7%）,阴道手术产的肌力异常率高于自然产及剖宫产（40.8% vs 32.5% & 27.2%）,分娩2次及以上的肌力异常率高于初次分娩（34.6% & 31.5% vs 29.1%）。多因素分析显示,城市户籍、文化程度高、分娩次数少是产后肌力的保护因素,阴道手术产是危险因素。结论 产后盆底肌力损伤的发生率高,分析造成产后盆底肌力损伤的相关因素,在孕前及围产期加强管理,做到早防早治,可以有效减少PFD的发生。     

Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development

Botulinum neurotoxins (BoNTs) show increasing therapeutic applications ranging from treatment of locally paralyzed muscles to cosmetic benefits. At first, in the 1970s, BoNT was used for the treatment of strabismus, however, nowadays, BoNT has multiple medical applications including the treatment of muscle hyperactivity such as strabismus, dystonia, movement disorders, hemifacial spasm, essential tremor, tics, cervical dystonia, cerebral palsy, as well as secretory disorders (hyperhidrosis, sialorrhea) and pain syndromes such as chronic migraine. This review summarizes current knowledge related to engineering of botulinum toxins, with particular emphasis on their potential therapeutic applications for pain management and for retargeting to non-neuronal tissues. Advances in molecular biology have resulted in generating modified BoNTs with the potential to act in a variety of disorders, however, in addition to the modifications of well characterized toxinotypes, the diversity of the wild type BoNT toxinotypes or subtypes, provides the basis for innovative BoNT-based therapeutics and research tools. This expanding BoNT superfamily forms the foundation for new toxins candidates in a wider range of therapeutic options.     

盆底康复操对产后盆底功能障碍性疾病产妇盆底肌力与情绪状态的改善作用

目的 探究盆底康复操对产后盆底功能障碍性疾病(PFD)产妇盆底肌力和情绪状态的改善作用.方法 选取77例产后盆底功能障碍性疾病产妇作为研究对象,依据随机数字表法分为A组(38例)和B组(39例).A组产妇接受常规产后康复方式,B组产妇在A组基础上采用盆底康复操.对比两组治疗前后焦虑自评量表(SAS)、抑郁自评量表(SD...     

盆底肌训练和电刺激在产后盆底肌力康复中的应用

目的:探讨盆底肌训练和电刺激在产后盆底肌力康复中的应用效果。方法:研究对象为2016年5月~2018年5月于某院接受治疗的足月妊娠产妇120例,采用抓阄的方式将其分为3组,即A、B对照组与研究组各40例。3组患者采用不同的治疗方法,对3组产妇的康复疗效进行对比分析。结果:从优良率的比较来看,研究组产妇治疗优良率较A、B对照组明显更高,3组组间比较差异具有统计学意义(P<0.05);且研究组产妇静息压、盆底收缩压亦明显高于A、B对照组,3组组间比较差异具有统计学意义(P<0.05)。结论:盆底肌训练和盆底电刺激在产后盆地肌力康复中的联合应用可有效提高产妇的产后康复效果,临床可积极推广采用。     

盆底肌功能锻炼对会阴切口的影响

目的 探讨盆底肌功能锻炼对会阴切口愈合的临床效果.方法 将86例经阴道分娩产妇随机分为两组,对照组43例采用常规会阴护理,观察组43例采用一对一盆底肌功能锻炼指导,并观察两组的临床疗效.结果 观察组的第3d、5d会阴切口无肿胀程度及Ⅰ级切口疼痛均明显高于对照组（均P＜ 0.05）.结论 孕产妇坚持盆底肌功能锻炼,可促进会阴切口的愈合,缩短病程,减少住院时间,值得临床应用和推广.     

盆底康复治疗对盆底功能障碍患者盆腔器官脱垂、尿失禁以及性功能的作用

目的:探讨盆底功能障碍实施盆底康复治疗对盆腔器官脱垂、尿失禁、性功能的影响。方法:取2018年1月~12月在某院治疗的100例盆底功能障碍患者分为对照组和观察组各50例,所有患者均行常规治疗,再给予观察组盆底康复治疗,对比分析两组治疗效果。结果:观察组盆腔器官脱垂发生率、尿失禁发生率、性功能障碍发生率均显著低于对照组(P<0.05);与对照组比较,观察组盆底收缩压、阴道静息压、Ⅰ类肌纤维的持续收缩压均更高,持续时间更长,Ⅱ类肌纤维快速收缩压更高,收缩个数更多,组间对比差异有统计学意义(P<0.05)。结论:女性产后盆底功能障碍在常规盆底训练的同时再进行盆底康复治疗,能有效恢复盆底肌力,明显改善患者盆底功能。     

产后盆底肌肉康复治疗尿失禁435例分析

目的：探讨产后盆底肌肉康复治疗对尿失禁等盆底功能障碍康复的临床效果。方法选择产后6～8周尿失禁患者435例,采用尿失禁问卷调查（ ICI－QSF问卷）及性功能问卷调查（ FSFI问卷）对产妇分别进行尿失禁（ SUI）调查、盆腔脏器脱垂（ POP－Q）分度及性生活质量问卷调查。比较盆底康复治疗前后Ⅰ类肌、Ⅱ类肌的肌力和疲劳度、阴道动态压的变化等盆底功能的改变。盆底肌肉康复治疗包括：仿生物电刺激、生物反馈、场景反射训练及Kegel锻炼。结果盆底肌肉康复治疗后,盆底功能明显提高,盆底肌力提高,疲劳度下降,阴道动态压上升：肌电值治疗前（5．6±1．8）μV,治疗8周后（15．1±4．6）μV（t＝3．6,P＜0．05）;阴道动态压治疗前（48．7±11．0）cmH2O,治疗4周后（86．3±5．1）cmH2O（t＝7．2,P＜0．01）;疲劳度明显改善（P＜0．01）,尿失禁治疗效果非常明显（t＝5．6,P＜0．05）,盆腔脏器脱垂改善明显,阴道前后壁脱垂治疗前Ⅱ度63例、Ⅲ度14例,治疗后Ⅱ度16例、Ⅲ度0例,缓解率82％;子宫脱垂治疗前172例,治疗后39例,缓解率77．3％;性功能得到明显改善,治疗前评分（78．00±20．45）分,治疗后评分（100．00±25．36）分（ t＝8．6,P＜0．01）。结论盆底肌肉康复治疗有效提高产后妇女的盆底功能,可达到治疗尿失禁、改善盆腔脏器脱垂、提高性生活质量的目的。     

产后盆底肌力情况及影响因素分析

目的 评估产后女性盆底肌力的状态,分析影响产后女性盆底肌力评级的因素.方法 以2014年3月至2016年2月在南京军区福州总医院接受盆底肌力检测的产后女性共2188例作为研究对象,利用PHENIX 2诊断系统平台,结合评价盆底肌肉综合肌力的指标Oxford评分(MOS)对盆底不同类别的肌纤维进行肌力评级,并对影响肌力评级的相关因素进行相关统计学分析.结果 ①PHENIX评估和MOS评分对盆底肌力的评定无显著差异(P＞0.05).②近4/5的产后女性盆底肌力的异常.③孕前体重越大及孕前BMI越小,盆底Ⅰ类肌异常的风险越大;而产后体重越小及产后BMI越大,盆底Ⅰ类肌的风险越大.④顺产、孕周和产次的增加,都可导致盆底Ⅱ类肌纤维肌力异常的风险增加.⑤选择适当的会阴切开方式(胎头位置、长度、角度)在短时间内不会影响盆底肌纤维肌力.⑥在42～60 d的研究范围内,年龄、身高、胎儿体重不是影响盆底肌力的相关因素.结论 妊娠及分娩是影响产后女性盆底肌力的重要因素,通过对产后盆底肌力情况及影响因素进行分析,对女性盆底肌功能障碍的防治具有指导意义.     

雌激素联合手术治疗对绝经后女性盆底功能障碍盆底肌力和尿流动力学指标的影响

目的观察雌激素联合手术治疗对绝经后女性盆底功能障碍的治疗效果。方法将120例绝经后女性盆底功能障碍患者分为雌激素治疗组、手术治疗组、雌激素联合手术治疗组,分别观察各组治疗前后盆底肌力变化,并进行尿流动力学检查。结果雌激素组与雌激素联合手术组治疗后盆底肌力增加;三组尿流动力学指标明显改善,且雌激素联合手术治疗组优于雌激素治疗组及手术治疗组,差异有统计学意义(P<0.05)。结论雌激素联合手术治疗绝经后女性盆底功能障碍疗效显著。     

生物反馈电刺激联合盆底肌训练在产后盆底康复治疗中的效果

目的观察生物反馈电刺激联合盆底肌训练在产后盆底康复治疗中的效果。方法 2010年1月至12月住院顺产初产妇(单胎)共100例,随机分成两组。观察组接受生物反馈电刺激联合盆底肌训练,对照组仅予盆底肌功能训练。6个月后随访盆底功能。结果观察组各项盆底功能障碍发生率为8.0%,显著低于对照组(40.0%,P<0.01)。观察组盆底肌收缩力评分(4.22±0.42)分,对照组为(3.18±0.35)分(P<0.05)。结论生物反馈电刺激联合盆底肌训练有利于产后盆底功能的恢复。     

盆底肌功能锻炼对孕产妇痔愈合的影响

目的探讨盆底肌功能锻炼对孕产妇痔愈合及盆底肌张力的影响。方法将103例孕妇合并痔随机分为观察组(49例)和对照组(54例)。对照组采用常规痔的卫生宣教方法护理,观察组加用盆底肌功能锻炼指导。结果观察组产后痔肿胀与对照组相比均有差异性(P<0.05).观察组产后盆底肌张力恢复也较对照组快(P<0.05)。结论对孕产妇合并痔予盆底肌功能锻炼,可促进痔的愈合;同时,盆底肌功能锻炼能促进盆底肌张力的恢复,可作为预防痔的保健措施。     

Use of botulinum toxin A in adult neurological disorders: efficacy, tolerability and safety

The protein botulinum neurotoxin A (BoNT/A) is one of seven distinct neurotoxins produced by Clostridium botulinum. BoNT/A blocks cholinergic synapses with an extremely high specificity and potency. Appropriately purified and diluted, BoNT/A serves as a reliable and well tolerated drug that is applied by local injection.The efficacy of BoNT/A is evident in the symptomatic therapy of disorders in which muscular hyperactivity plays a prominent role, such as focal dystonias and hemifacial spasm; in these disorders, BoNT/A is considered first-line therapy. BoNT/A is also beneficial in the treatment of both adults and children with spasticity of various causes. The pain that frequently accompanies these conditions is effectively reduced by BoNT/A. A genuine analgesic effect for BoNT/A unrelated to skeletal muscle spasmolysis has been suggested on the basis of in vitro and in vivo (animal) data. However, studies in humans designed to detect such an effect were negative, as were controlled studies of BoNT/A in patients with primary headache disorders.BoNT/A also acts on cholinergic synapses of the autonomic nervous system, and injection of BoNT/A into salivary glands significantly decreases the production of saliva. This may be beneficial for patients with Parkinson's disease, in whom the excessive production of saliva may be problematic.Overall, BoNT/A has been confirmed as an efficacious, predictable and well tolerated drug in an ever-increasing number of neurological disorders.     

电刺激生物反馈疗法联合盆底肌肉锻炼治疗女性盆底功能障碍性疾病220例疗效观察

目的探讨使用电刺激生物反馈疗法联合盆底肌肉锻炼治疗女性盆底功能障碍性疾病的疗效。方法选择2010年7月1日-2012年1月113在本院妇产科门诊通过筛查诊断为盆底功能障碍性疾病患者440例,随机分为治疗组220例和对照组220例,治疗组采用电刺激生物反馈疗法联合盆底肌肉锻炼治疗,对照组单纯采用盆底肌肉锻炼治疗,1个疗程后进行一般情况问卷调查尿失禁改善情况、性生活情况及行盆底肌肉功能评估,盆腔脏器脱垂测定,评价治疗效果。结果盆底肌收缩力、子宫脱垂、性生活质量、压力性尿失禁等方面两组均有不同程度改善．但观察组疗效明显优于对照组,差异有统计学意义（P〈0．05）。结论电刺激生物反馈疗法联合盆底肌肉锻炼治疗女性盆底功能障碍性疾病疗效满意,较单纯盆底肌肉锻炼效果好,值得临床应用和推广。     

Botulinum toxin in the treatment of OAB, BPH, and IC

Botulinum neurotoxins (BoNTs) are well known for their ability to potently and selectively disrupt and modulate neurotransmission. BoNT is currently undergoing regulatory evaluation for urological disorders in the United States and the European Union and is not FDA approved for urologic use. Overactive bladder (OAB) and benign prostatic hyperplasia (BPH) are common urologic conditions characterized by urinary frequency, urgency, nocturia, urge incontinence and, in the case of BPH, decreased urine flow that are currently being evaluated in clinical trials with BoNT-A. Interstitial cystitis (IC) is a chronic condition in which patients describe urinary frequency, urgency and associated bladder/pelvic pain. In the two former conditions, BoNT-A is currently being evaluated in Phase II or Phase III clinical trials as a therapeutic agent. Evidence for BoNT in the treatment of IC is limited to small case series. The purpose of this article is to provide up to date clinical evidence regarding the use of BoNT to treat these three urologic problems. For the sake of clarity, BoNT-A describes the use of Botox^® unless otherwise specified. In addition, when describing OAB, two sub-populations exist: those with OAB of neurogenic origin (NDO) and those with OAB of unknown (idiopathic) origin (IDO).     

产后盆底康复的个体化治疗100例临床分析

目的 探讨盆底电刺激用于产后盆底康复的有效性和可行性.方法 随机选取产后42天女性分为研究组和对照组,研究组行盆底电刺激治疗,对照组自行恢复,随访观察治疗效果.结果 行盆底电刺激康复的研究组产妇主观自觉症状好转,阴道弹性改善,盆底综合肌力提高,超声检查和性生活满意度改变明显,50名产后女性接受治疗,治疗次数从2～20次不等,平均7.8次,治疗时间20～30分钟,平均分钟22.5分钟.两组治疗后变化情况比较差异有显著性（P＜0.05）.结论 盆底电刺激用于产后盆底康复有效修复盆底组织结构与功能损伤,可作为产后盆底康复的常规内容.