Involvement of stem cell factor and its receptor tyrosine kinase c-kit in pain regulation
Involvement of stem cell factor and its receptor tyrosine kinase c-kit in pain regulation
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DOI：
10.1016/j.neuroscience.2008.02.073
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发表时间：
2008-06-02
期刊：
影响因子：
3.3
通讯作者：
Ito, S.
中科院分区：
文献类型：
--
作者：
Takagi, K.;Okuda-Ashitaka, E.;Ito, S.
C-kit受体酪氨酸激酶在背根神经节(DRG)和脊髓浅层的中小型神经元中表达。干细胞因子(SCF)是c-kit受体的配体，可诱导DRG突起生长，并支持表达c-kit的神经元存活。为了阐明SCF/c-kit受体系统在成年动物中的可能功能，我们用新开发的抗c-kit单抗H2C7研究了c-kit受体在脊髓和DRG中的表达与疼痛的关系。南加州大学。鞘内注射SCF可显著降低对机械刺激的缩足阈值，鞘内注射SCF最大剂量为10pg，可引起清醒小鼠的机械性痛觉过敏。鞘内SCF还显著缩短了小鼠对热刺激的缩足潜伏期。在降钙素基因相关肽(CGRP)阳性的DRG神经元中，c-kit受体共表达的比例为58.4%，而在异凝素B4阳性的DRG神经元中，c-kit受体的阳性表达比例仅为5.1%。在脊髓中，c-kit受体位于背角浅层，并与CGRP共同定位于DRG神经元的中央终末。新生辣椒素治疗选择性消除无髓C纤维导致脊髓浅层c-kit受体和CGRP表达显著减少。细胞大小分析显示，新生辣椒素处理和神经损伤后，中型DRG神经元c-kit受体的表达分别显著上调和下调。这些结果表明，c-kit受体主要在肽能小型DRG神经元中表达，可能参与外周和中枢的痛觉调节。(C)2008年IBRO。爱思唯尔有限公司出版。保留所有权利。
The c-kit receptor tyrosine kinase is expressed in a subpopulation of small- and medium-sized neurons of the dorsal root ganglia (DRG) and in the superficial layer of the spinal cord. Stem cell factor (SCF), a ligand of the c-kit receptor, induces neurite outgrowth from DRG and supports the survival of c-kit-expressing neurons. To clarify the possible function of the SCF/c-kit receptor system in the adult animal, we investigated the expression of c-kit receptor in the spinal cord and DRG in relation to pain by using H2C7, a newly developed anti-c-kit monoclonal antibody. S.c. and intrathecal injection of SCF markedly reduced the paw withdrawal threshold to mechanical stimuli and intrathecal SCF at 10 pg maximally induced mechanical allodynia in conscious mice. Intrathecal SCF also reduced the paw withdrawal latency to heat stimuli significantly but transiently. The c-kit receptor was co-expressed in 58.4% of calcitonin gene-related peptide (CGRP) -positive, but only 5.1% of isolectin B4-positive, DRG neurons. In the spinal cord, the c-kit receptor was detected in the superficial layer of the dorsal horn and co-localized there with CGRP in central terminals of DRG neurons. Selective elimination of unmyelinated C-fibers by neonatal capsaicin treatment resulted in marked reduction of the c-kit receptor and CGRP expression in the superficial layer of the spinal cord. Cell-size profiles showed that c-kit receptor expression was significantly up-regulated and down-regulated in medium-sized DRG neurons after neonatal capsaicin treatment and nerve injury, respectively. These results suggest that the c-kit receptor is mainly expressed in peptidergic small-sized DRG neurons and may be involved in pain regulation both peripherally and centrally. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.