Involvement of TRPM2 in peripheral nerve injury-induced infiltration of peripheral immune cells into the spinal cord in mouse neuropathic pain model.
Involvement of TRPM2 in peripheral nerve injury-induced infiltration of peripheral immune cells into the spinal cord in mouse neuropathic pain model.
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DOI：
10.1371/journal.pone.0066410
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kaneko S
中科院分区：
文献类型：
--
作者：
Isami K;Haraguchi K;So K;Asakura K;Shirakawa H;Mori Y;Nakagawa T;Kaneko S
最近的证据表明，瞬时受体电位美拉他汀2 （TRPM2）在免疫细胞中表达，在免疫和炎症反应中起重要作用。我们最近报道了巨噬细胞和脊髓小胶质细胞中表达的TRPM2参与了小鼠炎症性和神经性疼痛的发病机制，加重了外周和中枢前感觉性炎症反应。为了进一步阐明外周免疫细胞表达的TRPM2在神经性疼痛中的作用，我们通过野生型（WT）和TRPM2敲除（TRPM2- ko）小鼠杂交，利用骨髓（BM）嵌合小鼠研究了外周神经损伤诱导的神经性疼痛的发生以及免疫细胞（特别是巨噬细胞）向损伤神经和脊髓的浸润。制备了四种BM嵌合小鼠，将经辐照的WT或TRPM2-KO受体小鼠与WT或TRPM2-KO供体小鼠来源的绿色荧光蛋白阳性（GFP+） BM细胞（TRPM2BM+/Rec+、TRPM2BM - /Rec+、TRPM2BM+/Rec -和TRPM2BM - /Rec -小鼠）移植。在TRPM2BM+/Rec+小鼠中观察到的部分坐骨神经结束术引起的机械异常性痛在TRPM2BM - /Rec+、TRPM2BM+/Rec -和TRPM2BM - /Rec -小鼠中减弱。神经损伤14天后，嵌合小鼠坐骨神经中GFP+ bm来源细胞和Iba1/GFP双阳性巨噬细胞的数量无显著差异。在脊髓中，与TRPM2BM+/Rec+小鼠相比，三个TRPM2-KO嵌合小鼠组中GFP+ bm来源的细胞数量，特别是GFP/Iba1双阳性巨噬细胞数量显著减少。然而，嵌合小鼠中GFP - /Iba1+常驻小胶质细胞的数量没有差异。这些结果表明，TRPM2在外周免疫细胞特别是巨噬细胞浸润脊髓中发挥重要作用，而不是外周免疫细胞浸润损伤神经并激活脊髓小胶质细胞。TRPM2介导的脊髓巨噬细胞浸润可能参与神经性疼痛的发病机制。
Recent evidence suggests that transient receptor potential melastatin 2 (TRPM2) expressed in immune cells plays an important role in immune and inflammatory responses. We recently reported that TRPM2 expressed in macrophages and spinal microglia contributes to the pathogenesis of inflammatory and neuropathic pain aggravating peripheral and central pronociceptive inflammatory responses in mice. To further elucidate the contribution of TRPM2 expressed by peripheral immune cells to neuropathic pain, we examined the development of peripheral nerve injury-induced neuropathic pain and the infiltration of immune cells (particularly macrophages) into the injured nerve and spinal cord by using bone marrow (BM) chimeric mice by crossing wildtype (WT) and TRPM2-knockout (TRPM2-KO) mice. Four types of BM chimeric mice were prepared, in which irradiated WT or TRPM2-KO recipient mice were transplanted with either WT-or TRPM2-KO donor mouse-derived green fluorescence protein-positive (GFP+) BM cells (TRPM2BM+/Rec+, TRPM2BM–/Rec+, TRPM2BM+/Rec–, and TRPM2BM–/Rec– mice). Mechanical allodynia induced by partial sciatic nerve ligation observed in TRPM2BM+/Rec+ mice was attenuated in TRPM2BM–/Rec+, TRPM2BM+/Rec–, and TRPM2BM–/Rec– mice. The numbers of GFP+ BM-derived cells and Iba1/GFP double-positive macrophages in the injured sciatic nerve did not differ among chimeric mice 14 days after the nerve injury. In the spinal cord, the number of GFP+ BM-derived cells, particularly GFP/Iba1 double-positive macrophages, was significantly decreased in the three TRPM2-KO chimeric mouse groups compared with TRPM2BM+/Rec+ mice. However, the numbers of GFP–/Iba1+ resident microglia did not differ among chimeric mice. These results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than the infiltration of peripheral immune cells into the injured nerves and activation of spinal-resident microglia. The spinal infiltration of macrophages mediated by TRPM2 may contribute to the pathogenesis of neuropathic pain.
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影响因子：
16
作者：
Hara, Y;Wakamori, M;Mori, Y
通讯作者：
Mori, Y
影响因子：
5.5
作者：
Armstrong, DA;Major, JA;Hamilton, TA
通讯作者：
Hamilton, TA
影响因子：
5.5
作者：
Kraft, R;Grimm, C;Harteneck, C
通讯作者：
Harteneck, C
DOI：
10.1523/jneurosci.4569-09.2009
发表时间：
2009-11-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Costigan M;Moss A;Latremoliere A;Johnston C;Verma-Gandhu M;Herbert TA;Barrett L;Brenner GJ;Vardeh D;Woolf CJ;Fitzgerald M
通讯作者：
Fitzgerald M
影响因子：
4.4
作者：
Kielian, T;Barry, B;Hickey, WF
通讯作者：
Hickey, WF