Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome.
Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome.
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DOI：
10.1016/j.pain.2014.04.009
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发表时间：
2014-07
期刊：
影响因子：
7.4
通讯作者：
Thumbikat P
中科院分区：
文献类型：
--
作者：
Roman K;Done JD;Schaeffer AJ;Murphy SF;Thumbikat P
慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)影响高达15%的男性人口，以盆腔疼痛为特征。肥大细胞在小鼠实验性自身免疫性前列腺炎(EAP)模型中被认为是慢性盆腔疼痛发生的关键。在其他内脏疾病模型中，肥大细胞介质类胰蛋白酶-β及其同源受体蛋白水解酶激活受体2(PAR2)也参与介导疼痛。对CP/CPPS患者的前列腺液和尿液进行肥大细胞脱颗粒产物的检测。目的：探讨类胰蛋白酶β和PAR2在小鼠实验性自身免疫性前列腺炎中的表达。在存在或不存在PAR2表达和PAR2中和的情况下评估盆腔疼痛和炎症。CP/CPPS组与健康对照组比较，类胰蛋白酶-β和羧基肽酶A3均升高。Tryptase-β可诱导盆腔疼痛，并与其受体PAR2一起在EAP中升高。PAR2在EAP慢性盆腔疼痛的发生发展中起重要作用。背根神经节中的PAR2信号导致ERK1/2磷酸化和钙内流。使用抗体中和PAR2可减轻EAP患者的慢性盆腔疼痛。类胰蛋白酶-PAR2轴是EAP盆腔疼痛的重要介质，可能在CP/CPPS的发病机制中起一定作用。
Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine experimental autoimmune prostatitis (EAP). Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia lead to ERK1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS.
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发表时间：
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