Epigenetic transcriptional activation of monocyte chemotactic protein 3 contributes to long-lasting neuropathic pain

• DOI: 10.1093/brain/aws330
• Publication Date: 2013-01-31T04:57:53Z
• Authors: Satoshi Imai; Daigo Ikegami; Akira Yamashita; Toshikazu Shimizu; Michiko Narita; Keiichi Niikura; Masaharu Furuya; Yasuhisa Kobayashi; Kazuhiko Miyashita; Daiki Okutsu; Akira Kato; Atsushi Nakamura; Akiko Araki; Kazuo Omi; Masaya Nakamura; Hirotaka James Okano; Hideyuki Okano; Takayuki Ando; Hideyuki Takeshima; Toshikazu Ushijima; Naoko Kuzumaki; Tsutomu Suzuki; Minoru Narita
• Keywords: CCR2

A multiplex analysis for profiling the expression of candidate genes along with epigenetic modification may lead to a better understanding complex machinery neuropathic pain. In present study, we found that partial sciatic nerve ligation most remarkably increased monocyte chemotactic protein 3 (MCP-3, known as CCL7) total 33 541 in spinal cord, which lasted 4 weeks. This increase MCP-3 gene transcription was accompanied by decreased trimethylation histone H3 at Lys27 promoter. The associated its observed cord almost abolished interleukin 6 knockout mice ligation. Consistent these findings, single intrathecal injection recombinant proteins significantly messenger RNA decrease level promoter mice. Furthermore, deletion C–C chemokine receptor type 2 (CCR2) gene, encodes MCP-3, failed affect acceleration after robust protein, up weeks surgery, dorsal horn seen mostly astrocytes, but not microglia or neurons. On other hand, increases both and astrocytes were Moreover, this CCR2 deletion, whereas affected nerve-ligated lacked gene. We also either vivo vitro treatment caused activation. Under conditions, administration antibody suppressed within mouse pain-like behaviours injury. With use functional magnetic resonance imaging analysis, demonstrated induced dramatic signal intensity pain-related brain regions. These findings suggest dependent injury, serve facilitate astrocyte–microglia interaction could play critical role state.