Expression and Regulation of Cav3.2 T-Type Calcium Channels during Inflammatory Hyperalgesia in Mouse Dorsal Root Ganglion Neurons.
Expression and Regulation of Cav3.2 T-Type Calcium Channels during Inflammatory Hyperalgesia in Mouse Dorsal Root Ganglion Neurons.
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DOI：
10.1371/journal.pone.0127572
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ugawa S
中科院分区：
文献类型：
--
作者：
Watanabe M;Ueda T;Shibata Y;Kumamoto N;Shimada S;Ugawa S
Cav3.2亚型的T型钙通道在背根神经节（DRG）的初级感觉神经元中表达，这些通道有助于大鼠的伤害性疼痛和神经病理性疼痛。然而，关于这些通道在大鼠和小鼠疼痛处理中的作用有相互矛盾的报道。此外，T-型通道在持续性炎性痛觉过敏中的功能还知之甚少。我们进行了行为和全面的组织化学分析，以表征Cav3.2表达DRG神经元，并检查了角叉菜胶诱导的炎性痛觉过敏的C57 BL/6小鼠DRG中T型通道的调节。我们发现大约20%的小鼠背根神经节神经元表达Cav3.2 mRNA和蛋白。大多数Cav3.2阳性DRG神经元（69 ± 8%）的横截面积为300 - 700 μm2，估计直径为20 - 30 μm。这些通道与neurobeneficent-H（NF-H）或外周蛋白共定位。外周蛋白阳性细胞也重叠的isolectin B4（IB 4）和降钙素基因相关肽（CGRP）阳性的神经元，但不同的瞬时受体电位香草素1（TRPV 1）阳性神经元在正常小鼠状态。在角叉菜胶诱导的炎性痛觉过敏的小鼠中，Cav3.2通道，而不是Cav3.1或Cav3.3通道，在亚急性期在同侧DRG神经元中上调。Cav3.2表达的增加部分是由于Cav3.2免疫反应性神经元数量的增加;这种数量的增加对于TRPV 1阳性神经元特别显著。最后，在小鼠的急性和亚急性阶段，预先和定期足底内给予T型钙通道阻滞剂米贝拉地尔和NNC 55-0396分别显著降低和逆转了机械性痛觉过敏。这些数据表明，Cav3.2 T型通道参与炎症性痛觉过敏的发展，该通道可能发挥更大的作用，在亚急性期的炎性疼痛，由于增加与TRPV 1受体的共定位相比，在正常状态下。
The Cav3.2 isoform of the T-type calcium channel is expressed in primary sensory neurons of the dorsal root ganglion (DRG), and these channels contribute to nociceptive and neuropathic pain in rats. However, there are conflicting reports on the roles of these channels in pain processing in rats and mice. In addition, the function of T-type channels in persistent inflammatory hyperalgesia is poorly understood. We performed behavioral and comprehensive histochemical analyses to characterize Cav3.2-expressing DRG neurons and examined the regulation of T-type channels in DRGs from C57BL/6 mice with carrageenan-induced inflammatory hyperalgesia. We show that approximately 20% of mouse DRG neurons express Cav3.2 mRNA and protein. The size of the majority of Cav3.2-positive DRG neurons (69 ± 8%) ranged from 300 to 700 μm2 in cross-sectional area and 20 to 30 μm in estimated diameter. These channels co-localized with either neurofilament-H (NF-H) or peripherin. The peripherin-positive cells also overlapped with neurons that were positive for isolectin B4 (IB4) and calcitonin gene-related peptide (CGRP) but were distinct from transient receptor potential vanilloid 1 (TRPV1)-positive neurons during normal mouse states. In mice with carrageenan-induced inflammatory hyperalgesia, Cav3.2 channels, but not Cav3.1 or Cav3.3 channels, were upregulated in ipsilateral DRG neurons during the sub-acute phase. The increased Cav3.2 expression partially resulted from an increased number of Cav3.2-immunoreactive neurons; this increase in number was particularly significant for TRPV1-positive neurons. Finally, preceding and periodic intraplantar treatment with the T-type calcium channel blockers mibefradil and NNC 55-0396 markedly reduced and reversed mechanical hyperalgesia during the acute and sub-acute phases, respectively, in mice. These data suggest that Cav3.2 T-type channels participate in the development of inflammatory hyperalgesia, and this channel might play an even greater role in the sub-acute phase of inflammatory pain due to increased co-localization with TRPV1 receptors compared with that in the normal state.
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影响因子：
4.5
作者：
Comunanza, Valentina;Carbone, Emilio;Ursu, Daniel
通讯作者：
Ursu, Daniel
DOI：
10.1523/jneurosci.4991-12.2013
发表时间：
2013-05-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Btesh J;Fischer MJM;Stott K;McNaughton PA
通讯作者：
McNaughton PA
影响因子：
7.3
作者：
Okubo, Kazumasa;Matsumura, Midori;Kawabata, Atsufumi
通讯作者：
Kawabata, Atsufumi
DOI：
10.1124/jpet.103.060814
发表时间：
2004-04-01
影响因子：
3.5
作者：
Huang, LP;Keyser, BM;Li, M
通讯作者：
Li, M
影响因子：
11.4
作者：
Bourinet, E;Alloui, A;Nargeot, J
通讯作者：
Nargeot, J