Acid-sensing ion channel 3 expression in mouse knee joint afferents and effects of carrageenan-induced arthritis.

Acid-sensing ion channel 3 expression in mouse knee joint afferents and effects of carrageenan-induced arthritis.
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DOI:
10.1016/j.jpain.2008.10.010
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发表时间:
2009-03
期刊:
The journal of pain
影响因子:
--
通讯作者:
Sluka KA
Sluka KA
中科院分区:
其他
文献类型:
--
作者:
Ikeuchi M;Kolker SJ;Sluka KA

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关节炎与局部pH值的降低有关。在酸敏感离子通道(ASIC)中,ASIC 3对这种pH值变化最敏感,在背根神经节(DRG)中大量表达,并且对于继发性痛觉过敏的发展至关重要。本研究的目的是使用小鼠中的急性关节炎疼痛模型研究ASIC 3的上调。我们通过逆行标记和免疫组织化学方法检测了支配膝关节的DRG神经元中ASIC 3的表达,并与角叉菜胶诱导的关节炎进行了比较。我们还研究了ASIC 3 +/+和ASIC 3-/-小鼠之间DRG表型的差异。31%的膝关节传入纤维中存在ASIC 3免疫反应性,并且主要存在于小细胞中。关节炎症后,ASIC 3免疫反应阳性神经元的数量显著增加了50%。CGRP在ASIC 3 +/+和ASIC 3-/-小鼠中增加相似。不表达CGRP的ASIC 3阳性神经元的索马胞体大小分布向直径较小的神经元偏移。我们的研究结果表明,ASIC 3在急性关节炎疼痛中起着重要作用。具体而言,我们提出,ASIC 3上调沿着CGRP和表型变化的ASIC 3免疫反应神经元没有CGRP负责角叉菜胶诱导的关节炎继发性痛觉过敏的发展。
Arthritis is associated with decreases in local pH. Of the acid sensing ion channels (ASIC), ASIC3 is most sensitive to such a pH change, abundantly expressed in dorsal root ganglion (DRG), and critical for the development of secondary hyperalgesia. The purpose of this study was to investigate the upregulation of ASIC3 using an acute arthritic pain model in mice. We examined ASIC3 expression in DRG neurons innervating the knee joint with and without carrageenan-induced arthritis by means of retrograde labeling and immunohistochemistry. We also examined the difference of DRG phenotype between ASIC3+/+ and ASIC3-/- mice. ASIC3 immunoreactivity was present in 31% of knee joint afferents and dominantly in small cells. After joint inflammation, ASIC3-immunoreactive neurons significantly increased in number by 50%. CGRP increased similarly in both ASIC3+/+ and ASIC3-/- mice. Soma size distribution of ASIC3-immunoreactive neurons without CGRP expression was shifted to smaller diameter neurons. Our results suggest that ASIC3 plays an important role in acute arthritic pain. Specifically, we propose that ASIC3 upregulation along with CGRP and phenotypic change in ASIC3-immunoreactive neurons without CGRP are responsible for the development of secondary hyperalgesia following carrageenan-induced arthritis.
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