Spatio-temporal expression and functional involvement of transient receptor potential vanilloid 1 in diabetic mechanical allodynia in rats.
Spatio-temporal expression and functional involvement of transient receptor potential vanilloid 1 in diabetic mechanical allodynia in rats.
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瞬时受体电位 Vanilloid 1 在大鼠糖尿病机械异常性疼痛中的时空表达和功能参与
DOI：
10.1371/journal.pone.0102052
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Li YQ
中科院分区：
文献类型：
--
作者：
Cui YY;Xu H;Wu HH;Qi J;Shi J;Li YQ
糖尿病性神经病理性疼痛（DNP）是糖尿病（DM）最常见的临床表现之一，以机械异常性疼痛（DMA）为主要特征。然而，其分子机制尚未完全阐明。在这项研究中，我们研究了一个主要的伤害性通道蛋白瞬时受体电位香草酸1（TRPV 1）的时空表达，并分析了其功能参与鞘内（i.t.）TRPV 1拮抗剂在链脲佐菌素（STZ）诱导的DMA大鼠模型中的应用。Western blot和免疫荧光染色结果显示，STZ处理后14 d（DMA 14 d），背根神经节（DRG）神经元索马胞体中TRPV 1蛋白表达显著增加，而脊髓和皮肤中TRPV 1蛋白表达（主要来自DRG神经元的中枢和外周突起）在DMA 7 d时已开始增加，DMA 14 d时达到高峰。qRT-PCR实验证实，在DMA 7 d时，TRPV 1 mRNA在DRG中的表达显著上调，表明TRPV 1蛋白在索马体中有优先翻译，但在DMA条件下该蛋白优先分布于突起。免疫双染细胞计数法提示，TRPV 1阳性神经元可能是体积较小的CGRP阳性神经元。最后，单次或多次鞘内应用非特异性或特异性TRPV 1拮抗剂，钌红和辣椒平，在不同的剂量，有效地减轻DMA，虽然前者的效果更突出和持久。这些结果共同表明，TRPV 1的表达动态变化过程中的DMA和这种蛋白质可能发挥重要作用，在DRG神经元的机械伤害感受，可能是通过促进CGRP的释放。
Diabetic neuropathic pain (DNP) is one of the most common clinical manifestations of diabetes mellitus (DM), which is characterized by prominent mechanical allodynia (DMA). However, the molecular mechanism underlying it has not fully been elucidated. In this study, we examined the spatio-temporal expression of a major nociceptive channel protein transient receptor potential vanilloid 1 (TRPV1) and analyzed its functional involvement by intrathecal (i.t.) application of TRPV1 antagonists in streptozocin (STZ)-induced DMA rat models. Western blot and immunofluorescent staining results showed that TRPV1 protein level was significantly increased in the soma of the dorsal root ganglion (DRG) neurons on 14 days after STZ treatment (DMA 14 d), whereas those in spinal cord and skin (mainly from the central and peripheral processes of DRG neurons) had already been enhanced on DMA 7 d to peak on DMA 14 d. qRT-PCR experiments confirmed that TRPV1 mRNA level was significantly up-regulated in the DRG on DMA 7 d, indicating a preceding translation of TRPV1 protein in the soma but preferential distribution of this protein to the processes under the DMA conditions. Cell counting assay based on double immunostaining suggested that increased TRPV1-immunoreactive neurons were likely to be small-sized and CGRP-ergic. Finally, single or multiple intrathecal applications of non-specific or specific TRPV1 antagonists, ruthenium red and capsazepine, at varying doses, effectively alleviated DMA, although the effect of the former was more prominent and long-lasting. These results collectively indicate that TRPV1 expression dynamically changes during the development of DMA and this protein may play important roles in mechanical nociception in DRG neurons, presumably through facilitating the release of CGRP.
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DOI：
10.1159/000268118
发表时间：
2009
期刊：
Digestive diseases (Basel, Switzerland)
影响因子：
--
作者：
Holzer P;Holzer-Petsche U
通讯作者：
Holzer-Petsche U
影响因子：
2.5
作者：
Ivanusic, Jason J.
通讯作者：
Ivanusic, Jason J.
影响因子：
4.7
作者：
Morioka, N;Takeda, K;Nakata, Y
通讯作者：
Nakata, Y
影响因子：
--
作者：
Morrow, Thomas J
通讯作者：
Morrow, Thomas J
影响因子：
25
作者：
Naeini, RS;Witty, MF;Bourque, CW
通讯作者：
Bourque, CW