Liedman Ragner, Skillern Laurence, James Ian, McLeod Alison, Grant Lee, Akerlund Mats
Department of Obstetrics and Gynecology, University Hospital of Lund, Sweden.
Acta Obstet Gynecol Scand. 2006;85(4):451-7. doi: 10.1080/00016340500432432.
The myometrial hyperactivity and reduced uterine blood flow of primary dysmenorrhea is to a large extent caused by increased vasopressin secretion. A new therapeutic approach for this condition is to develop antagonists of uterine vasopressin V1a receptors. We studied a test model of vasopressin-induced dysmenorrhea in healthy, sterilized women and compared responses against those in dysmenorrheic subjects.
Eight women with primary dysmenorrhea and eight sterilized, healthy women participated in recordings of intrauterine pressure and experienced pain on days 1-2 of two menstruations. We tried to identify biochemical markers in plasma of uterine ischemia. Furthermore, the effects of repeated bolus injections of 10 pmol/kg b w of vasopressin or placebo on these parameters were assessed.
The vasopressin injections caused statistically significant increases in the area under the intrauterine pressure curve (AUC) in both healthy volunteers and patients with dysmenorrhea, the overall responses being greater in healthy volunteers. The experienced pain measured by visual analog scale in individual dysmenorrheic subjects tended to show higher maximal post-dose scores for the vasopressin injections than for placebo. Maximum visual analog scale scores and maximum AUCs in individual subjects tended to be related. Mean creatine kinase MB levels were higher in women with dysmenorrhea than in healthy subjects both before and after vasopressin administration, the converse being observed for C-reactive protein levels.
The present model appears to be useful for evaluating new drugs for the treatment of primary dysmenorrhea.
原发性痛经的子宫肌层活动亢进和子宫血流量减少在很大程度上是由血管加压素分泌增加所致。针对这种情况的一种新的治疗方法是开发子宫血管加压素V1a受体拮抗剂。我们研究了健康绝育女性中血管加压素诱导的痛经测试模型,并将其反应与痛经患者的反应进行了比较。
八名原发性痛经女性和八名绝育的健康女性参与了子宫内压记录,并在两个月经周期的第1 - 2天经历疼痛。我们试图确定子宫缺血血浆中的生化标志物。此外,评估了以10 pmol/kg体重重复推注血管加压素或安慰剂对这些参数的影响。
血管加压素注射导致健康志愿者和痛经患者的子宫内压曲线下面积(AUC)在统计学上显著增加,健康志愿者的总体反应更大。痛经个体受试者通过视觉模拟量表测量的疼痛体验显示,血管加压素注射后的最大剂量后评分往往高于安慰剂。个体受试者的最大视觉模拟量表评分和最大AUC往往相关。血管加压素给药前后,痛经女性的平均肌酸激酶MB水平均高于健康受试者,而C反应蛋白水平则相反。
目前的模型似乎有助于评估治疗原发性痛经的新药。