女性慢性盆腔痛的神经生物学研究进展

盆腔痛是女性常见妇科疾病之一,以慢性盆腔痛为主,对女性的姿势、平衡能力等都有着较大的影响,严重威胁着女性患者的生活质量和生命健康。但是目前关于女性慢性盆腔痛发生的生物学基础尚不清楚,病因也尚不明确,且对慢性盆腔痛的评估和治疗也比较复杂,给女性慢性盆腔痛的治疗和康复带来了较大的困难。为了给女性盆腔痛预防和治疗提供进一步的理论基础,拟对女性内生殖系统和外生殖系统的神经支配、中枢神经系统影像改变和疼痛易感性、细胞因子和外周神经纤维的相互作用、炎症因子在降低外周神经敏感性中的作用、钠离子通道介导神经元疼痛信号的传导、神经元的激酶信号传导通路激活进行综述,重点探讨信号通路和细胞因子等因素在疼痛发生中的作用。     

生殖系统肿瘤引起的盆腔痛

盆腔痛是女性生殖系统良性或恶性肿瘤常见的症状之一。生殖系统肿瘤引起盆腔痛的原因、临床表现和治疗有一定的特殊性，现简述如下。１　肿瘤性盆腔痛的原因　　文献［１］报告，肿瘤引起疼痛的原因有５种：①肿瘤本身引起的疼痛；②肿瘤治疗引起的疼痛；③与肿瘤间接有关的疼痛；④与肿瘤无关的伴发症；⑤心理和社会因素。女性生殖系统肿瘤引起盆腔痛的原因，临床最常见的是肿瘤本身引起，其次是肿瘤治疗引起，其它原因较少见。有关调查报道［２］，我国１９种原发癌患病率高低顺序中，女性生殖器癌居第９位。引起疼痛的主要原因是肿瘤的进…     

妇科恶性肿瘤与盆腔痛

盆腔痛是女性生殖系统恶性肿瘤常见的症状之一，主要是由肿瘤侵犯内脏器官、骨组织及神经发生广泛转移，或经放疗、化疗后的并发症所引起。文章对妇科恶性肿瘤引起盆腔痛的类型、原因、临床症状和治疗方法进行了阐述。     

生殖系统炎症引起的盆腔痛

盆腔痛是妇科常见的症状之一,生殖系统炎症是引起盆腔疼痛最主要的原因。按炎症发生的部位,大致可分为上、下生殖道炎症。前者即感染侵袭内生殖器,发生于子宫及其周围结缔组织、输卵管、卵巢及盆腔腹膜的炎症,称为盆腔炎;盆腔炎按其起病急缓、病程长短又有急、慢性之分。后者即炎症发生于下生殖道如外阴炎、阴道炎及宫颈炎,一般以外阴瘙痒、白带增多为主。因此,生殖系统炎症引起的盆腔痛主要指由急、慢性盆腔炎所致的急、慢性下腹部及腰骶部疼痛。而慢性盆腔痛是指病程超过６个月以上的非周期性盆腔疼痛。１　生殖系统炎症引起盆腔痛…     

子宫内膜异位症相关疼痛的免疫学研究进展

子宫内膜异位症(endometriosis),简称内异症,是一个广泛影响年轻育龄期女性的疾病,其主要的表现为不孕不育和慢性盆腔痛。慢性盆腔痛严重影响患者的生存质量,而免疫系统的紊乱是目前对于内异症的研究热点。与内异症相关的异常免疫细胞主要包括巨噬细胞、肥大细胞、中性粒细胞等;相关的炎性介质或细胞因子包括神经营养因子(NTs)家族的神经生长因子(NGF)、脑源性神经营养因子(BDNF),还有肿瘤坏死因子α(TNF-α)、单核细胞化学引诱物-1(MCP-1)、白细胞介素(IL)等。这些免疫调节细胞和因子通过神经炎性反应、成神经作用、中枢和外周的神经敏化、改变细胞膜电位差以及调节内分泌等功能,导致了内异症患者的疼痛症状。本文旨在回顾目前关于内异症相关疼痛的免疫学研究进展。     

黎小斌运用当归芍药散治疗慢性盆腔疼痛的经验

当归芍药散来源于《金匮要略》,具有活血、柔肝、健脾、祛瘀的功效,原为治疗妇人腹中诸痛。慢性盆腔疼痛定义为源自盆腔器官、结构的疼痛症候群,持续时间超过6个月,疼痛通常与消极的认知行为、性行为和负面情感相关,也可与下尿路、生殖系统、胃肠道、盆底肌筋膜或性功能障碍有关,危害女性身心健康。黎小斌教授运用当归芍药散治疗慢性盆腔疼痛有良效。     

骶神经调节治疗慢性盆腔痛的研究进展

慢性盆腔痛(CPP)指一种病因不明、病史复杂的疾病,严重时会影响患者的生活质量,其治疗方法以药物及手术治疗为主,一部分患者并不能获得满意的疗效。骶神经调节(SNM)术是利用介入技术将刺激电极放置骶神经孔,通过低频电脉冲兴奋或抑制神经通路,进而影响并调节骶神经支配的靶器官功能,从而达到治疗效果的一种神经调节技术。目前研究发现,SNM在常规治疗失败的CPP患者中取得了不错的效果,其术后疼痛视觉模拟评分有明显改善,特别是伴有泌尿系统症状的女性患者,其可能的机制为调节疼痛传导通路及盆底肌张力,但还需要大样本长期随访以进一步评估。     

神经阻滞疗法治疗慢性盆腔痛及痛经

女性慢性盆腔痛与痛经的主要治疗方法包括药物治疗、手术治疗以及神经阻滞疗法等。当药物及手术治疗效果不佳或者并非首选时,神经阻滞疗法是值得期待的一种疗法。研究表明,化学性神经阻滞疗法中的上腹下丛神经阻滞、阴部神经阻滞和交感神经阻滞中的奇神经节阻滞及星状神经节阻滞术治疗女性慢性盆腔痛及痛经均有一定疗效,在临床上不失为治疗方法的一个选择。但其治疗的长期效果、治疗的副反应及适应证的选择都有待进一步研究。     

Hedgehog通路对女性生殖系统肿瘤的作用

Hedgehog(HH)信号通路对女性生殖系统的发育起重要作用,并在多种肿瘤细胞中异常激活,提示其活化可能与肿瘤的发生和进展有关。本文将对近年来HH通路在女性生殖系统肿瘤中的研究进展及其抑制剂的临床应用作一综述,旨在为相关肿瘤的靶向治疗提供临床依据。     

下腹上丛神经阻滞在妇科手术后镇痛中的应用

下腹上丛(SHP)神经位于骶岬前方,包含传导盆腔脏器痛觉的感觉神经纤维。影像学引导下行SHP神经阻滞可有效缓解盆腔子宫内膜异位症及恶性肿瘤导致的慢性盆腔痛。全子宫切除或子宫动脉栓塞手术中同时行SHP神经阻滞可明显减少术后镇痛药物的使用,显著降低疼痛评分。SHP神经阻滞操作简便快捷,不良反应少见,是一种安全高效的缓解盆腔疼痛的方法。     

巨噬细胞在子宫内膜异位症神经纤维及血管生成中的作用及机制

子宫内膜异位症（endometriosis,EMs）是育龄期女性常见疾病,其发病机制目前尚未明确,其中神经纤维及血管生成是促进疾病进展、产生慢性盆腔痛及子宫内膜异位病灶增大的重要机制,而其形成原因亦非常复杂,很可能与EMs免疫微环境的改变密切相关。而作为EMs免疫因素重要成分的巨噬细胞,在疾病发生、发展中异常募集并产生表型及功能的改变,分泌多种促炎及抗炎细胞因子,引起神经信号的过度兴奋和通路转导异常,并参与血管内皮生长因子（VEGF）通路的调控,对神经血管的生成有重要作用。总结在EMs中巨噬细胞表型功能变化对神经纤维异常生成及盆腹腔中血管增生的作用及其潜在机制,为针对巨噬细胞与EMs神经血管生成的靶向治疗可以干预炎症过程、周围神经和血管的生成提供理论支持,为解析EMs的发病机制提供新的思路。     

Obturator Neuromodulation with Laparoscopic Placement of an Obturator Lead for the Treatment of Intractable Opioid-Dependent Chronic Pelvic Pain due to Obturator Neuralgia

Chronic pelvic pain (CPP) is a common condition in women that can have a devastating effect on quality of life. Some of the most severe forms of CPP are related to peripheral nerve injuries, causing persistent neuropathic pain. We present a case of a young woman with severe opioid-dependent chronic pelvic and right groin pain due to obturator neuralgia. She had failed amultitude of treatments, including multiple medications, manual physical therapy, nerve blocks, surgical neurolysis, and spinal cord stimulation, without significant benefit. She underwent a trial of peripheral neuromodulation of the obturator nerve with laparoscopic placement of a quadripolar lead. During the 6-day trial, she experienced almost complete relief of her pain; therefore, she underwent permanent implantation of an intermittent pulse generator. Over the next 6 months, she was completely weaned off chronic opioids. At 23 months postimplantation, she had essentially no pain and was no longer receiving any analgesic, antidepressant, or membrane-stabilizing medications.     

Surgical management of chronic pelvic pain

Chronic pelvic pain is a common debilitating condition affecting women and presents a major challenge to healthcare providers. Laparoscopy is the only test capable of diagnosing peritoneal endometriosis and adhesions. Gynaecologists have, therefore, seen it as an essential tool in the assessment of women with chronic pelvic pain. This article explores the role of surgery in the management of chronic pelvic pain. The approach to women with chronic pain must be therapeutic, supportive and sympathetic. Depending on the severity of disease found, ideal practice is to diagnose and remove the disease surgically at the same time during laparoscopy. A maximum surgical effort must be expended to resect all endometriosis, restore normal pelvic anatomy, resect nerve fibres and treat surgically accessible disease.     

The role of laparoscopy in the diagnosis and treatment of conditions associated with chronic pelvic pain

Laparoscopy is a useful tool for the diagnosis and treatment of conditions associated with chronic pelvic pain. In the evaluation of chronic pelvic pain, laparoscopic techniques vary from conservative procedures, such as pain mapping, excision, and nerve ablation, to more extensive procedures like oophorectomy and hysterectomy. Although useful for diagnosis, laparoscopy continues to have a controversial role in the treatment of chronic pelvic pain.     

Bilateral oophorectomy and hysterectomy in the treatment of intractable pelvic pain associated with pelvic congestion.

OBJECTIVE--To determine whether bilateral oophorectomy combined with hysterectomy is an effective treatment for chronic pelvic pain due to congestion. DESIGN--Prospective non-randomized single centre study. SETTING--Tertiary referral centre to a specialist pelvic pain clinic in a teaching hospital. SUBJECTS--36 women, 33 of whom had failed to obtain long term relief of pain on medical therapy. MAIN OUTCOME MEASURES--Relief of pain, coital frequency, and effect on daily life. Histology of uterus and ovaries. RESULTS--Median pain score on visual analogue scale fell from a pre-operative value of 10 to 0 at one year. Twelve of the 36 women had some residual pain at one year postoperatively, but in only one woman was the pain affecting her daily life. Thirty women were noted to have pelvic tenderness pre-operatively, at one year, 26 had no tenderness and four minimal tenderness on pelvic examination. The median frequency of sexual intercourse increased from once per month preoperatively to eight times per month one year postoperatively. The uterus was histologically normal in 25 women, adenomyosis was present in eight of whom two had ovarian endometriosis. Fibroids were present in three and endometriosis was found confined to the ovaries in one woman. Multiple peripheral cysts were present in the ovaries of 25 women. CONCLUSION--Bilateral oophorectomy combined with hysterectomy and hormone replacement therapy is an effective treatment for chronic pelvic pain due to venous congestion, which has failed to respond to medical treatment and leads to restoration of normal coital function and daily life.     

Chronic inflammation of the peritoneum and vagina: review of its significance, immunologic pathogenesis, investigation and rationale for treatment

Chronic inflammation is not an infrequent histologic finding in symptomatic gynecologic patients. It is present in 14.6% of peritoneal biopsies in women with chronic pelvic pain in whom no other cause of pain is evident. It is found in almost all vaginal biopsies in noninfected women with dyspareunia and discharge of vaginal mucosal origin. It represents a local immunologically activated inflammatory disorder. When investigations are car ried out as to whether it is a local representation of a systemic disorder, numerous systemic inflammatory and autoimmune disorders are discovered. A study of chronic pain reveals that the immune system is intimately involved in the production, conduction and exacerbation of pain and of its clinicalfeatures, such as hyperalgesia and allodynia. Immune modification using local steroids and disease-modifying antirheumatic drugs, such as hydroxychloroquine, are known to inhibit inflammatory cells and cytokines, such as interleukin-1, interleukin-6 and tumor necrosis factor, which are responsible for pain and tissue damage. These drugs are found to be effective in the treatment of chronic pelvic pain when of an inflammatory nature and for symptomatic chronic inflammation of the vagina.     

A double-blind randomised controlled trial of laparoscopic uterine nerve ablation for women with chronic pelvic pain

OBJECTIVE: To determine the effectiveness of laparoscopic uterine nerve ablation (LUNA) for chronic pelvic pain in women with endometriosis and women with no laparoscopic evidence of endometriosis. DESIGN: A prospective double-blind randomised controlled trial (RCT). SETTING: Single-centre, secondary-level gynaecology outpatient service and tertiary-level pelvic pain and endometriosis outpatient service in Auckland, New Zealand. POPULATION: One hundred and twenty-three women undergoing laparoscopy for investigation and management of chronic pelvic pain, 56 with no laparoscopic evidence of endometriosis and 67 with endometriosis. METHODS: Women were randomised from the two populations, firstly those with no evidence of endometriosis and secondly those undergoing laparoscopic surgical treatment for endometriosis, to receive LUNA or no LUNA. Participant and assessor blinding was employed. Follow up for pain outcomes was undertaken at 24 hours, 3 months and 12 months. MAIN OUTCOME MEASURES: Changes in non-menstrual pelvic pain, dysmenorrhoea, deep dyspareunia and dyschezia were assessed primarily by whether there was a decrease in visual analogue score for these types of pain of 50% or more from baseline and additionally whether there was a significantly different change in median visual analogue score. The numbers requiring further surgery or starting a new medical treatment for pelvic pain and complications were also measured. RESULTS: There was a significant reduction in dysmenorrhoea at 12 month follow up in women with chronic pelvic pain in the absence of endometriosis who underwent LUNA (median change in visual analogue scale (VAS) from baseline -4.8 versus-0.8 (P= 0.039), 42.1%versus 14.3% experiencing a successful treatment defined as a 50% or greater reduction in visual analogue pain scale for dysmenorrhoea (P= 0.045). There was no significant difference in non-menstrual pelvic pain, deep dyspareunia or dyschezia in women with no endometriosis undergoing LUNA versus no LUNA. The addition of LUNA to laparoscopic surgical treatment of endometriosis was not associated with a significant difference in any pain outcomes. CONCLUSIONS: LUNA is effective for dysmenorrhoea in the absence of endometriosis, although there is no evidence of effectiveness of LUNA for non-dysmenorrhoeic chronic pelvic pain or for any type of chronic pelvic pain related to endometriosis.     

The role of laparoscopy in the management of pelvic pain in women of reproductive age

Objective: To review the diagnostic and therapeutic roles of laparoscopy in women of reproductive age with acute and chronic pelvic pain.Data Identification: Studies relating to the use of laparoscopy in women with acute and chronic pelvic pain were identified through the literature and MEDLINE searches.Conclusion(s): Laparoscopy has an important place in the management of conditions that cause acute pelvic pain in women of reproductive age, including ectopic pregnancy, pelvic inflammatory disease, tubo-ovarian abscess, and adnexal torsion. The procedure frequently facilitates the diagnosis and provides the necessary access for surgical treatment. Prompt diagnosis and effective management prevent complications and help preserve fertility. The role of laparoscopy in women with chronic pelvic pain is more controversial and limited, but abnormal laparoscopic findings are detected in approximately 60% of those who have undergone a multidisciplinary investigation and received a tentative clinical diagnosis. The access provided by laparoscopy permits the effective surgical treatment of many of the conditions encountered, including endometriosis, pelvic adhesions, ovarian lesions, and symptomatic uterine retroversion.     

Pathophysiology of endometriosis-associated pain: A review of pelvic and central nervous system mechanisms

Although pain is one of the main symptoms women with endometriosis present with, there is poor correlation between symptom severity and disease burden and the underlying biological mechanisms by which pain arises are still only poorly understood. We briefly review the neurobiology of pain before considering mechanisms that may be specifically relevant in the context of endometriosis. The role of pelvic factors such as new nerve fibre growth, peritoneal fluid and inflammation is explored with a particular focus on studies where these factors have been associated with pain symptoms rather than just being compared between women with endometriosis and disease-free controls. We then consider the role of the central nervous system and associated systems, including the stress axis and psychological factors, in the modulation of pain. The potential for changes in these systems to be a cause and/or a consequence of the pain and how they might explain some of the known associations between endometriosis and other somatic symptoms is discussed. The chapter concludes by considering the implications of these mechanisms on treatment strategies for these women.     

Quantitative Sensory Testing in Gynaecology: Improving Preoperative and Postoperative Pain Diagnosis

Chronic pelvic pain presents difficulties for women suffering its complex presentation. It also presents difficulties for clinicians involved in diagnosing and managing the problem. We review here clinically relevant information related to visceral pathology and its association with peripheral and central aspects of pain hypersensitivity. We address why surgery appears to be successful in some cases but less than successful in others, and what cautionary indicators should be taken into account. A categorization of chronic pelvic pain based on our understanding of pain physiology and mechanisms involved is proposed. The benefits of multidimensional sensory and pain testing in gynaecological care are reviewed.