Department of Urology, Bács-Kiskun County Teaching Hospital, Kecskemét, Hungary.
Institute of Surgical Research, University of Szeged, Szeged, Hungary.
Neurourol Urodyn. 2018 Feb;37(2):690-698. doi: 10.1002/nau.23376. Epub 2017 Aug 1.
This study was initiated to investigate the involvement of neutrophil leukocyte activation in neurogenic inflammation, a process also involved in human urinary pathologies, elicited in the rat urinary bladder by the local administration of capsaicin, the archetypal TRPV1 agonist. The contribution of afferent nerves and sensory neuropeptides to leukocyte activation in the urinary bladder microcirculatory bed was examined.
Following a 15-min topical application of capsaicin (50 μM), leukocyte-endothelial interactions were examined for an observation period of 45 min with intravital microscopy. Expression of adhesion molecules E-selectin and ICAM-1 implicated in these interactions was assessed by immunohistochemistry. Selective sensory denervation was performed by neonatal treatment with capsaicin. The role of the TRPV1 receptor and two sensory neuropeptides (CGRP and substance P [SP]) were studied using the selective antagonists capsazepine, CGRP and RP67580, respectively.
Capsaicin induced rapid increases in leukocyte rolling and adhesion and increased the expression of E-selectin and ICAM-1 in the postcapillary venules. Sensory chemodenervation via capsaicin and also TRPV1 receptor antagonism effectively prevented these changes. A similar reduction was observed in leukocyte adhesion after topical application of CGRP or RP67580, but only CGRP reduced the capsaicin-evoked leukocyte rolling.
Topical application of capsaicin induces early neurogenically mediated cellular microcirculatory inflammatory reactions via the activation of the TRPV1 receptor and the release of CGRP and SP from sensory nerves in the bladder. Co-administration of SP and CGRP receptor antagonists may ameliorate microcirculatory inflammatory changes elicited by capsaicin in the urinary bladder.
本研究旨在探讨中性粒细胞白细胞激活在神经源性炎症中的作用，这种炎症过程也涉及人类泌尿道疾病，由辣椒素（TRPV1 激动剂的原型）在大鼠膀胱中的局部给药引发。本研究还研究了传入神经和感觉神经肽对膀胱微循环床中白细胞激活的贡献。
在局部应用辣椒素（50μM）15 分钟后，通过活体显微镜观察 45 分钟，检查白细胞-内皮相互作用。通过免疫组织化学评估参与这些相互作用的粘附分子 E-选择素和 ICAM-1 的表达。通过新生期用辣椒素处理进行感觉神经去神经支配。使用选择性 TRPV1 受体拮抗剂辣椒素和两种感觉神经肽（CGRP 和 P 物质[SP]）分别研究 TRPV1 受体和两种感觉神经肽（CGRP 和 P 物质[SP]）的作用。
辣椒素诱导白细胞滚动和黏附的快速增加，并在后毛细血管静脉中增加 E-选择素和 ICAM-1 的表达。通过辣椒素和 TRPV1 受体拮抗剂进行感觉化学去神经支配可有效预防这些变化。局部应用 CGRP 或 RP67580 后，白细胞黏附也观察到类似的减少，但只有 CGRP 减少了辣椒素诱导的白细胞滚动。
辣椒素的局部应用通过激活 TRPV1 受体和从膀胱感觉神经释放 CGRP 和 SP，诱导早期神经介导的细胞微循环炎症反应。共同给予 SP 和 CGRP 受体拮抗剂可能会改善膀胱中辣椒素引起的微循环炎症变化。
