Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.
Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.
复制标题
慢性前列腺炎小鼠模型中的伤害性和炎症介质上调。
DOI：
10.1097/j.pain.0000000000000201
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发表时间：
2015-08
期刊：
影响因子：
7.4
通讯作者：
Gebhart GF
中科院分区：
文献类型：
--
作者：
Schwartz ES;Xie A;La JH;Gebhart GF
慢性非细菌性前列腺炎在成年男性中很常见，其特征是在没有可识别的原因的情况下盆腔区域的泌尿生殖系统疼痛。令人惊讶的是，前列腺的感觉神经支配以及使其神经敏感的介体几乎没有受到关注。因此，我们描述了一种慢性前列腺炎的小鼠模型，重点研究了前列腺的神经支配以及器官炎症如何影响背根节(DRG)中前列腺体传入体中可能的伤害性标记的基因表达以及前列腺中的介质。从前列腺逆行追踪(快蓝，FB)可见，胸腰段(TL)和腰骶段(LS)背根节是前列腺传入体节的主要来源。在前列腺炎性反应(前列腺内注射酵母多糖)后，伤害性标志物(如Trp、Trek和P2X通道)在FB标记的TL和LS Somata中上调长达四周。注射酵母多糖后14、21和28天，前列腺炎性反应明显，单核细胞浸润，肥大细胞类胰蛋白酶活性显著升高。在四周的炎症过程中，白介素10和神经生长因子在前列腺中也显著上调。前列腺炎小鼠的旷场疼痛相关行为(例如，站立)没有变化，这表明没有持续的伤害感，但降低腹压的戒断阈值显著降低。炎症前列腺组织中IL-10、肥大细胞类胰蛋白酶和神经生长因子的升高与探腹阈值降低和支配前列腺的背根节伤害性标志物表达上调同步。这些结果为研究慢性前列腺炎疼痛的机制提供了洞察力和方向。
Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue, FB) from the prostate revealed that thoracolumbar (TL) and lumbosacral (LS) DRG are the principal sources of somata of prostate afferents. Nociceptive markers (e.g., TRP, TREK and P2X channels) were upregulated in FB-labeled TL and LS somata for up to four weeks after inflaming the prostate (intra-prostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21 and 28 days after zymosan injection. Interleukin-10 and NGF were also significantly upregulated in the prostate throughout the four weeks of inflammation. Open field pain-related behaviors (e.g., rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for study of mechanisms underlying pain in chronic prostatitis.