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Title: Involvement of TRPM2 in Peripheral Nerve Injury-Induced Infiltration of Peripheral Immune Cells into the Spinal Cord in Mouse Neuropathic Pain Model.
Authors: Isami, Kouichi
Haraguchi, Kayo
So, Kanako
Asakura, Kayoko
Shirakawa, Hisashi  kyouindb  KAKEN_id
Mori, Yasuo  kyouindb  KAKEN_id
Nakagawa, Takayuki  kyouindb  KAKEN_id
Kaneko, Shuji  kyouindb  KAKEN_id
Author's alias: 中川, 貴之
Issue Date: 30-Jul-2013
Publisher: Public Library of Science
Journal title: PloS one
Volume: 8
Issue: 7
Thesis number: e66410
Abstract: 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 (TRPM2(BM+/Rec+), TRPM2(BM-/Rec+), TRPM2(BM+/Rec-), and TRPM2(BM-/Rec-) mice). Mechanical allodynia induced by partial sciatic nerve ligation observed in TRPM2(BM+/Rec+) mice was attenuated in TRPM2(BM-/Rec+), TRPM2(BM+/Rec-), and TRPM2(BM-/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 TRPM2(BM+/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.
Rights: © 2013 Isami et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI(Published Version): 10.1371/journal.pone.0066410
PubMed ID: 23935822
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