Department of Urology, Tohoku Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
Int Urogynecol J. 2023 Jun;34(6):1211-1218. doi: 10.1007/s00192-022-05335-x. Epub 2022 Aug 30.
In women with chronic pelvic pain (CPP), interstitial cystitis/bladder pain syndrome (IC/BPS) and endometriosis frequently coexist. The mechanism of these diseases coexisting is explained by cross-sensitization between endometriosis and IC/BPS. The overlapped symptoms may be related to cross-sensitization with transient receptor potential vanilloid 1 (TRPV1) and/or transient receptor potential ankyrin 1 (TRPA1) hyperexpression. This study was aimed at exploring whether bladder hypersensitivity is evoked in the surgically induced ectopic endometriosis rat and whether TRPV1 and/or TRPA1 play a vital role.
A total of 63 Sprague-Dawley female rats were divided into two groups, 39 for physiological examination and 24 for molecular analysis. Surgical induction of ectopic endometriosis (ENDO, n=27), surgical sham treatment (n=18), and treatment for endometriosis by GnRH analog (ENDO-G) (n=18) were performed. Bladder function was investigated by cystometry (for TRPV1 in the sham [n=6] and ENDO [n=9] groups and for TRPA1 in the sham [n=6], ENDO [n=9], and ENDO+G [n=9] groups), and TRPV1 and TRPA1 mRNA expressions were measured using real-time qPCR in the bladder and dorsal root ganglia (DRGs).
On cystometry, the relative intercontraction interval (ICI) after/before resiniferatoxin (RTx; TRPV1 activator) infusion to the bladder showed no significant difference between the two groups, whereas relative ICI after/before allyl isothiocyanate (AITC; TRPA1 activator) infusion was significantly lower in the ENDO group than in the sham group. TRPA1 mRNA expression in the bladder and L5 DRG was considerably higher in the ENDO group than in the sham group on real-time qPCR. TRPA1 mRNA hyperexpression and bladder hypersensitivity after AITC infusion were reduced in the ENDO-G group.
Bladder cross-sensitization in ENDO rats occurs in association with hyperexpression of TRPA1 at both the DRG and the bladder mucosa. This can be understood by the "cross-sensitization of endometriosis to bladder" theory explaining overlapping symptoms among BPS/IC and ectopic endometriosis.
在患有慢性盆腔疼痛（CPP）的女性中，间质性膀胱炎/膀胱疼痛综合征（IC/BPS）和子宫内膜异位症经常同时存在。这些疾病同时存在的机制可以用子宫内膜异位症和 IC/BPS 之间的交叉致敏来解释。重叠的症状可能与瞬时受体电位香草醛 1（TRPV1）和/或瞬时受体电位锚蛋白 1（TRPA1）过度表达有关。本研究旨在探讨手术诱导的异位子宫内膜异位症大鼠是否会引起膀胱过敏，以及 TRPV1 和/或 TRPA1 是否起重要作用。
共 63 只 Sprague-Dawley 雌性大鼠分为两组，39 只为生理检查，24 只为分子分析。进行手术诱导异位子宫内膜异位症（ENDO，n=27）、手术假手术处理（n=18）和 GnRH 类似物治疗子宫内膜异位症（ENDO-G，n=18）。通过膀胱测压法（用于 TRPV1 的 sham [n=6]和 ENDO [n=9]组，以及用于 TRPA1 的 sham [n=6]、ENDO [n=9]和 ENDO+G [n=9]组）研究膀胱功能，并用实时 qPCR 测量膀胱和背根神经节（DRG）中 TRPV1 和 TRPA1 的 mRNA 表达。
在膀胱测压法中，膀胱内树脂毒素（TRPV1 激活剂）输注前后的相对间歇收缩间期（ICI）在两组之间无显著差异，而膀胱内丙烯基异硫氰酸酯（TRPA1 激活剂）输注前后的相对 ICI 在 ENDO 组显著低于 sham 组。实时 qPCR 显示，ENDO 组膀胱和 L5 DRG 的 TRPA1 mRNA 表达明显高于 sham 组。ENDO-G 组的 TRPA1 mRNA 过度表达和 AITC 输注后的膀胱过敏反应降低。
ENDO 大鼠的膀胱交叉致敏与 DRG 和膀胱黏膜上的 TRPA1 过度表达有关。这可以用“子宫内膜异位症对膀胱的交叉致敏”理论来解释 BPS/IC 和异位子宫内膜异位症之间重叠的症状。
