Schwartz Erica S, Xie Amy, La Jun-Ho, Gebhart G F
Department of Anesthesiology, Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Pain. 2015 Aug;156(8):1537-1544. doi: 10.1097/j.pain.0000000000000201.
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) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate 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 4 weeks of inflammation. Open-field pain-related behaviors (eg, 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 the study of mechanisms underlying pain in chronic prostatitis.
慢性非细菌性前列腺炎以盆腔区域生殖泌尿疼痛为特征，且无明确病因，在成年男性中很常见。令人惊讶的是，前列腺的感觉神经支配以及使其神经支配敏感化的介质很少受到关注。因此，我们对慢性前列腺炎的小鼠模型进行了表征，重点关注前列腺神经支配以及器官炎症如何影响背根神经节（DRG）中前列腺传入躯体感觉神经元的假定伤害性标记物的基因表达和前列腺中的介质。从前列腺进行逆行示踪（快蓝）显示，胸腰段和腰骶段DRG是前列腺传入神经元躯体的主要来源。在前列腺发炎（前列腺内注射酵母聚糖）后长达四周的时间里，快蓝标记的胸腰段和腰骶段躯体中的伤害性标记物（例如，瞬时受体电位、TREK和P2X通道）上调。酵母聚糖注射后14、21和28天，组织学上可见前列腺炎症明显，有单核细胞浸润且肥大细胞类胰蛋白酶活性显著增加。在整个炎症的4周期间，前列腺中的白细胞介素10和神经生长因子也显著上调。前列腺发炎的小鼠在旷场试验中与疼痛相关的行为（例如，竖毛）未发生变化，表明没有持续性伤害感受，但对下腹部压力的撤防阈值显著降低。发炎前列腺中白细胞介素10、肥大细胞类胰蛋白酶和神经生长因子的增加与腹部探查阈值降低以及支配前列腺的DRG躯体中伤害性标记物上调同时发生。这些结果为慢性前列腺炎疼痛的潜在机制研究提供了见解和方向。
