A life of pelvic pain

Pelvic pain associated with menstruation, i.e., dysmenorrhea, is a chronic pelvic pain that not only interferes with a woman's wellbeing for a large part of her life but also often co-occurs with other chronic painful conditions such as interstitial cystitis and irritable bowel syndrome and others. Little has been known about mechanisms underlying these chronic pelvic pains. This paper reviews 37 years of research in my laboratory at Florida State University on such mechanisms. Our research, mostly on rats, has contributed to the following findings: (1) Female reproductive organs are innervated in a topographic fashion by afferents in the pelvic (vagina/cervix) and hypogastric (cervix/uterine horn) nerves. (2) The input contributes to uterine and vaginal perceptions (nociception) that are modified by reproductive status. (3) Throughout the CNS, neurons responsive to stimulation of the reproductive tract also respond to stimulation of skin and other internal organs, in a manner modifiable by reproductive status and peripheral pathophysiology. (4) This dynamic physiological convergence may reflect extensive anatomical divergence of and interconnections between pathways entering the CNS via gateways through the spinal cord, dorsal column nuclei, and solitary nucleus. (5) The convergence also indicates the existence of extensive cross-system, viscero-visceral interactions within the CNS, that, while organized for coherent bodily functioning, serves as a substrate by which pathophysiology in one organ can influence physiology and responses to pathophysiology in other organs. (6) Some cross-system effects observed so far include: (a) Bladder inflammation reduces the rate of uterine contractions and the effects of drugs on the uterus. (b) Colon inflammation produces signs of inflammation in the otherwise healthy bladder and uterus. (c) A surgical model of endometriosis produces vaginal hyperalgesia, exacerbates pain behaviors induced by a ureteral stone, and reduces volume voiding thresholds if the bladder. These cross-system effects, which likely involve CNS mechanisms, likely also underlie co-occurrence of painful clinical conditions. Research continues on details of these mechanisms and their relevance for clinical diagnosis and therapy. None of this work could have been done without collegial support of colleagues and technical staff at Florida State University.     

基质金属蛋白酶-2、3及其组织抑制剂TIMP-1在子宫内膜异位症中的表达

目的探讨基质金属蛋白酶(MMP-2、MMP-3)及其抑制剂(TIMP-1)在子宫内膜异位症发生及发展中的作用.方法采用免疫组化SP法分别测定MMP-2、MMP-3 、TIMP-1在卵巢子宫内膜异位症异位内膜60例(A组),子宫腺肌症异位内膜40例(B组),子宫肌瘤子宫内膜30例(对照组C)的表达强度.结果 A、B组中MMP-2、MMP-3的表达强度明显高于对照组(P<0.05)而TIMP-1的表达明显低于对照组(P<0.05);A、B组间MMP-2、MMP-3 、TIMP-1 的表达无明显差异(P>0.05).结论在子宫内膜异位症中MMP-2、MMP-3的过度表达及TIMP-1的低表达可能与内异症的发生与发展有关.     

孤啡肽与子宫内膜异位不孕的相关研究

目的探讨子宫内膜异位症(内异症)不孕患者血孤啡肽含量的变化及对生殖内分泌的影响.方法采用放射免疫法测定21例内异症不孕妇女(不孕组)、23例单纯输卵管阻塞不孕妇女(对照组)及30例健康妇女(正常组)血孤啡肽及卵泡刺激素(FSH)、黄体生成素(LH)的含量.结果 (1)不孕组妇女血孤啡肽及FSH、LH的含量分别为(29.61±6.33)ng.L-1 、(2.03±0.32)IU.L-1及(6.43±1.89)IU.L-1,对照组妇女血孤啡肽及FSH、LH的含量分别为(10.18±3.64)ng.L-1、(4.05±0 51)IU.L-1及(15.05±4.26)IU.L-1,正常组分别为(11.35±3.71)ng.L-1、(3.82±0.46)IU.L-1及(12.63±3.18)IU.L-1.(2)内异症不孕组妇女血孤啡肽水平显著高于对照组及正常组(P<0.01及P<0.05).(3)不孕组妇女血FSH、LH的含量显著低于对照组及正常组(P<0.01及P<0.05).(4)内异症不孕妇女血孤啡肽及FSH、LH水平显著负相关(P<0.05).结论孤啡肽与子宫内膜异位不孕的发生发展密切相关,其机理可能与抑制FSH及LH的分泌有关.     

子宫内膜异位症不孕妇女腹腔液对精子运动及穿卵的影响

目的探讨子宫内膜异位症（内异症）性不孕妇女的腹腔液对人精子运动及穿卵率的影响。方法将行诊断性腹腔镜检查的不孕妇女40例分为内异症组20例,根据r—AFS分期：早期（Ⅰ／Ⅱ）12例,晚期（Ⅲ／Ⅳ）8例,对照组20例为其它原因不孕者,酶标双抗体夹心法（ELISA）测定两组患者腹腔液肿瘤坏死因子（TNF—α）的含量;正常人精液按1：1比例和两组腹腔液共同孵育,测定精子运动参数（平均曲线速度、平均直线速度、平均路径速度、直线前向运动百分率）和去透明带地鼠卵穿透试验的变化。结果内异症组腹腔液TNF—α含量高于其它原因不孕组（P〈0．05）,且晚期内异症组的TNF-α又明显高于早期患者（P〈0．05）;内异症组四项精子运动参数指标均低于对照组,与TNF—α含量呈负相关（P〈0．05）;内异症组穿卵数值明显低于对照组（P〈0．05）。结论体外观察内异症不孕患者腹腔液对精子活力及穿卵受精能力有明显抑制作用,内异症患者腹腔液内TNF—α值升高与疾病程度正相关,可能是导致不孕的机理之一。     

RANTES基因多态性与子宫内膜异位症的相关性研究

目的研究RANTES基因启动子区-28C/G的多态性与子宫内膜异位症的关系。方法应用聚合酶链反应-限制性酶切片段长度多态性技术(PCR-RFLP)并进行测序的方法检测子宫内膜异位症患者46例(内异症组),非子宫内膜异位症患者35例(对照组)。结果子宫内膜异症组RANTES-28C/C、C/G两种基因型分布频率分别为84.78%、15.22%,对照组RANTES-28C/C、C/G两种基因型分布频率分别为85.71%、14.29%;两组间的组之间的基因型分布频率比较差异无显著性(P>0.05)。RANTES基因-28位点C、G等位基因型在内异症组中的分布频率分别为92.39%、7.61%,在对照组中分别为92.86%、7.14%,两组间等位基因型频率比较差异无统计学意义(P>0.05)。结论 RAN-TES启动子区-28C/G基因多态性与子宫内膜异位症遗传易感性无关联。     

Increase in the production of interleukin-6, interleukin-10, and interleukin-12 by lipopolysaccharide-stimulated peritoneal macrophages from women with endometriosis

PROBLEM: To verify whether the peritoneal macrophage (PM) is activated in endometriosis. METHOD OF STUDY: We examined the synthesis of nitric oxide (NO), total antioxidant, interleukin (IL)-6, IL-10, and IL-12 by cultured PMs, which were either unstimulated or stimulated with lipopolysaccharide (LPS), from women with endometriosis (early, n = 12; advanced, n = 11) or without endometriosis (n = 13). RESULTS: After stimulation with 2 ng/mL LPS for 24 hr, PMs from women with early-stage endometriosis secreted more NO, IL-6, and IL-10 than the controls. Higher IL-12 levels were noted in women with advanced endometriosis when compared with the controls. After 2 ng/mL-LPS stimulation for 24 hr, we also detected higher total antioxidant levels in the advanced-endometriosis group than those in the early-endometriosis group. CONCLUSION: The increased production of IL-6, IL-10, and IL-12 by stimulated PMs confirmed previous observations that the PM is the principle source of these cytokines in peritoneal fluid.     

DNA甲基转移酶1和组蛋白去乙酰化酶1在子宫内膜异位症在位内膜的表达

目的 探讨DNA甲基转移酶1（DNMT1）和组蛋白去乙酰化酶1（HDAC1）在子宫内膜异位症患者子宫内膜中的表达及其两者在子宫内膜异位症发生、发展中的作用。方法 选取子宫内膜异位症患者在位内膜18例, 无子宫内膜异位症的对照子宫内膜20例,应用免疫组织化学法测定DNMT1的分布,应用免疫印迹法检测内膜组织中DNMT1和HDAC1蛋白的表达。结果 免疫组织化学提示,DNMT1主要分布于子宫内膜腺上皮细胞和间质细胞的胞核;子宫内膜异位症在位内膜中DNMT1的表达强度显著高于对照组子宫内膜（P<0.01）。免疫印迹发现,子宫内膜异位症在位内膜DNMT1和HDAC1蛋白的表达高于对照组子宫内膜, 差异有统计学意义（P<0.05）;且两者的表达呈正相关 （P<0.05）。结论 DNMT1和HDAC1在EMs患者的高表达可能在子宫内膜异位症的发生、发展中起着重要作用。     

The Peritoneal Leptin,MCP‐1 and TNF‐α in the Pathogenesis of Endometriosis‐Associated Infertility

Citation Tao Y, Zhang Q, Huang W, Zhu H, Zhang D, Luo W. The peritoneal leptin, MCP‐1 and TNF‐α in the pathogenesis of endometriosis‐associated infertility. Am J Reprod Immunol 2011; 65: 403–406 Problem To explore the roles of leptin, monocyte chemotactic protein (MCP)‐1, and tumour necrosis factor (TNF)‐α in the peritoneal fluid (PF) in the pathogenesis of endometriosis‐associated infertility. Method of study Leptin, MCP‐1, and TNF‐α levels in the PF from 28 infertile women with endometriosis (study group), 23 women with fallopian‐associated infertility (controls), and 24 women with myoma (controls) were determined by performing enzyme‐linked immunosorbent assay (ELISA). Result Leptin and TNF‐α levels in the PF showed no significant difference among three groups. The MCP‐1 level in patients with endometriosis was higher than those in fallopian‐associated infertility group and myoma group (P < 0.01). There was a positive correlation between leptin and MCP‐1 levels in the PF of patients with endometriosis (P < 0.05). Conclusion Peritoneal leptin and MCP‐1 play important roles in the pathogenesis of infertility in the early stage of endometriosis.     

干细胞因子与MMP-9在子宫内膜异位症中的表达及意义

目的探讨SCF与MMP-9在子宫内膜异位症(EM s)患者的异位和在位内膜组织中的表达。方法采用免疫组化SABC法,检测28例EM s病人异位内膜(异位内膜组)及在位内膜组织(在位内膜组)SCF与MMP-9的表达,并与30例非EM s病人在位内膜(对照组)进行比较。结果 (1)异位和在位内膜组中,SCF阳性表达平均光密度(MOD)均高于对照组(P<0.05)。(2)异位和在位内膜组中,MMP-9阳性表达也均高于对照组的0.20±0.04(P<0.05)。(3)SCF与MMP-9在异位内膜组I/II期与III/IV期中的表达无显著性差异(P>0.05)。(4)异位和在位内膜组中,SCF与MMP-9的表达呈正相关(P<0.05)。结论 SCF与MMP-9在EM s的发生、发展中可能起着重要作用。     

Interleukin 1 alpha (IL1A) polymorphisms and risk of endometriosis in Iranian population: a case-control study

Abstract

Endometriosis is one of the most common gynecological diseases and a major cause of pain and infertility. It is influenced by genetic, epigenetic, and environmental factors. Recently, genome-wide association studies have revealed a strong association between IL1A single nucleotide polymorphisms (SNPs) and increased risk of endometriosis in Japanese women. The aim of the present study was to evaluate the association of three IL1A SNPs, rs17561, rs1304037, and rs2856836 with the risk of endometriosis in Iranian population. Totally, 105 women with diagnosis of endometriosis and 102 healthy women as control group were included. Three SNPs of the IL1A, rs17561?G/T, rs1304037 A/G, and rs2856836 T/C, were genotyped by PCR and RFLP. The rs2856836?TC genotype was significantly higher (p?=?.002; OR?=?3.1, 95% CI: 1.5–6.5) in the patients (28.1%) than the control group (12.7%). The rs2856836?CC genotype was significantly higher (p?=?.047; OR?=?2.3, 95% CI: 1.0–5.3) in the patients (17.5%) than the control group (10.8%). The rs2856836 C allele was significantly higher (p?=?.001; OR?=?2.2, 95% CI: 1.4–3.6) in the patients (31.6%) than the control group (17.2%). The IL1A rs2856836 T/C SNP was associated with susceptibility to endometriosis and the rs2856836 C allele may increase the risk of endometriosis in Iranian women.