Tingåker Berith K, Ekman-Ordeberg Gunvor, Facer Paul, Irestedt Lars, Anand Praveen
Karolinska Institutet, Department of Woman and Child Health, Division of Obstetrics and Gynecology, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
Reprod Biol Endocrinol. 2008 Feb 12;6:8. doi: 10.1186/1477-7827-6-8.
Cervical ripening is a prerequisite for a normal obstetrical outcome. This process, including labor, is a painful event that shares features with inflammatory reactions where peripheral nociceptive pathways are involved. The capsaicin and heat receptor TRPV1 is a key molecule in sensory nerves involved in peripheral nociception, but little is known regarding its role in the pregnant uterus. Therefore, the aim of this study was to investigate human corpus and cervix uteri during pregnancy and labor and non-pregnant controls for the presence of TRPV1.
We have investigated human uterine corpus and cervix biopsies at term pregnancy and parturition. Biopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8), in labor (n = 8) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 8). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial frozen sections were examined immunohistochemically using specific antibodies to TRPV1 and nerve markers (neurofilaments/peripherin).
In cervix uteri, TRPV1-immunoreactive fibers were scattered throughout the stroma and around blood vessels, and appeared more frequent in the sub-epithelium. Counts of TRPV1-immunoreactive nerve fibers were not significantly different between the three groups. In contrast, few TRPV1-immunoreactive fibers were found in nerve fascicles in the non-pregnant corpus, and none in the pregnant corpus.
In this study, TRPV1 innervation in human uterus during pregnancy and labor is shown for the first time. During pregnancy and labor there was an almost complete disappearance of TRPV1 positive nerve fibers in the corpus. However, cervical innervation remained throughout pregnancy and labor. The difference in TRPV1 innervation between the corpus and the cervix is thus very marked. Our data suggest that TRPV1 may be involved in pain mechanisms associated with cervical ripening and labor. Furthermore, these data support the concept that cervix uteri may be the major site from which labor pain emanates. Our findings also support the possibility of developing alternative approaches to treat labor pain.
宫颈成熟是正常产科结局的前提条件。这个过程,包括分娩,是一个痛苦的事件,与涉及外周伤害性感受途径的炎症反应有共同特征。辣椒素和热受体TRPV1是参与外周伤害感受的感觉神经中的关键分子,但关于其在妊娠子宫中的作用知之甚少。因此,本研究的目的是调查妊娠和分娩期间的人体子宫体和宫颈以及非妊娠对照中TRPV1的存在情况。
我们研究了足月妊娠和分娩时的人体子宫体和宫颈活检组织。活检组织取自足月剖宫产时子宫切口的上缘(n = 8)、分娩时(n = 8)以及子宫切除术后非妊娠子宫的相应区域(n = 8)。宫颈活检组织经阴道从宫颈前唇获取。使用针对TRPV1和神经标志物(神经丝/外周蛋白)的特异性抗体对连续冰冻切片进行免疫组织化学检查。
在子宫颈中,TRPV1免疫反应性纤维散布于整个基质和血管周围,并且在上皮下更为常见。三组之间TRPV1免疫反应性神经纤维的计数无显著差异。相比之下,在非妊娠子宫体的神经束中发现的TRPV1免疫反应性纤维很少,而在妊娠子宫体中未发现。
在本研究中,首次展示了妊娠和分娩期间人体子宫中TRPV1的神经支配情况。在妊娠和分娩期间,子宫体中TRPV1阳性神经纤维几乎完全消失。然而,宫颈神经支配在整个妊娠和分娩期间持续存在。因此,子宫体和宫颈之间TRPV1神经支配的差异非常明显。我们的数据表明,TRPV1可能参与与宫颈成熟和分娩相关的疼痛机制。此外,这些数据支持子宫颈可能是分娩疼痛产生的主要部位这一概念。我们的发现还支持开发治疗分娩疼痛替代方法的可能性。