Expression of TRPV1 channels after nerve injury provides an essential delivery tool for neuropathic pain attenuation.
Expression of TRPV1 channels after nerve injury provides an essential delivery tool for neuropathic pain attenuation.
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DOI：
10.1371/journal.pone.0044023
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kitagawa J
中科院分区：
文献类型：
--
作者：
Zakir HM;Mostafeezur RM;Suzuki A;Hitomi S;Suzuki I;Maeda T;Seo K;Yamada Y;Yamamura K;Lev S;Binshtok AM;Iwata K;Kitagawa J
神经损伤后，瞬时受体电位香草样蛋白1 （TRPV1）通道的表达增加，可能促进QX-314进入伤害性神经元，从而实现有效和选择性的疼痛缓解。在本研究中，我们假设QX-314/辣椒素(QX-CAP) -诱导的有害行为阻断水平可以作为TRPV1通道功能表达的间接体内测量。我们采用QX-CAP联合检测大鼠下肺泡神经（IAN）横断后再生神经元中TRPV1的功能表达。我们通过分析心理外侧皮肤机械刺激的逃逸阈值，评估了该组合对IAN横断后不同时间点疼痛阈值的影响。IAN横断2周后，未见QX-CAP介导的机械性痛觉过敏阻滞，提示TRPV1通道无功能性表达。这些结果通过三叉神经节（TG）再生神经元的免疫组织化学染色证实。这表明TRPV1通道的表达是QX-CAP介导的阻断的必要条件。此外，我们发现，在IAN横断后3周和4周，QX-CAP的应用使逃避阈值逐渐增加，这与再生TG神经元中检测到的TRPV1通道水平增加相平行。免疫组织化学分析还显示，与有髓鞘神经元相比，无髓鞘神经元在横断IAN后再生较慢。我们还发现TRPV1的表达向髓鞘神经元转移。我们的研究结果表明，神经损伤调节了再生神经元中TRPV1的表达模式，QX-CAP诱导的阻断的有效性取决于再生神经元中TRPV1功能性受体的可用性。本研究结果还表明，基于QX-CAP的方法可以作为一种新的行为工具，用于检测各种病理条件下TRPV1表达的动态变化。
Increased expression of the transient receptor potential vanilloid 1 (TRPV1) channels, following nerve injury, may facilitate the entry of QX-314 into nociceptive neurons in order to achieve effective and selective pain relief. In this study we hypothesized that the level of QX-314/capsaicin (QX-CAP) - induced blockade of nocifensive behavior could be used as an indirect in-vivo measurement of functional expression of TRPV1 channels. We used the QX-CAP combination to monitor the functional expression of TRPV1 in regenerated neurons after inferior alveolar nerve (IAN) transection in rats. We evaluated the effect of this combination on pain threshold at different time points after IAN transection by analyzing the escape thresholds to mechanical stimulation of lateral mental skin. At 2 weeks after IAN transection, there was no QX-CAP mediated block of mechanical hyperalgesia, implying that there was no functional expression of TRPV1 channels. These results were confirmed immunohistochemically by staining of regenerated trigeminal ganglion (TG) neurons. This suggests that TRPV1 channel expression is an essential necessity for the QX-CAP mediated blockade. Furthermore, we show that 3 and 4 weeks after IAN transection, application of QX-CAP produced a gradual increase in escape threshold, which paralleled the increased levels of TRPV1 channels that were detected in regenerated TG neurons. Immunohistochemical analysis also revealed that non-myelinated neurons regenerated slowly compared to myelinated neurons following IAN transection. We also show that TRPV1 expression shifted towards myelinated neurons. Our findings suggest that nerve injury modulates the TRPV1 expression pattern in regenerated neurons and that the effectiveness of QX-CAP induced blockade depends on the availability of functional TRPV1 receptors in regenerated neurons. The results of this study also suggest that the QX-CAP based approach can be used as a new behavioral tool to detect dynamic changes in TRPV1 expression, in various pathological conditions.
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