Assessment of spinal cord chemokine signaling in the mechanism of neuropathic pain.

• Project/Area Number: 25460721
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: Kyushu University
• Principal Investigator: Saitoh Hidetoshi 九州大学, 薬学研究科(研究院), 准教授 (90444794)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 神経障害性疼痛 / ミクログリア / ケモカイン / グリア

Outline of Final Research Achievements

Neuropathic pain is a debilitating pain state, which is often caused by injury to the nervous system. Hallmark symptoms of neuropathic pain include tactile allodynia and thermal hyperalgesia, which are refractory to currently available treatments such as non-steroidal anti-inflammatory drugs and opioids. The mechanism underlying development of neuropathic pain remains largely unknown. Therefore, unraveling the molecular and cellular basis of the development and maintenance of neuropathic pain is essential for the discovery of new treatments.
In this study, we reported that upregulation of CCL3 and CCR5 was induced in the spinal cord after nerve injury, and that the CCR5 antagonist can alleviate neuropathic pain.Further more, in primary cultured microglia,we found that P2Y12 receptor activation induced CCL3 expression via NFAT signaling.
These results suggest that CCL3-CCR5 axis is crucial in the mechanism of neuropathic pain, and CCR5 might be a therapeutic target for neuropathic pain.

Research Products

• [Journal Article] 慢性痛とグリア細胞 (2015)
  • Author(s): 齊藤秀俊，津田誠，井上和秀
  • Journal Title: Clinical Neuroscience Volume: 33 Pages: 860-861
• [Journal Article] Interferon regulatory factor 8 expressed in microglia contributes to tactile allodynia induced by repeated cold stress in rodents. (2014)
  • Author(s): Akagi T, Matsumura Y, Yasui M, Minami E, Inoue H, Masuda T, Tozaki-Saitoh H, Tamura T, Mizumura K, Tsuda M, Kiyama H, Inoue K.
  • Journal Title: Journal of Pharmacological Science Volume: 126 Pages: 172-176
  • Peer Reviewed
• [Journal Article] Involvement of the chemokine CCL3 and the purinoceptor P2X7 in the spinal cord in paclitaxel-induced mechanical allodynia. (2014)
  • Author(s): Ochi-ishi R, Nagata K, Inoue T, Tozaki-Saitoh H, Tsuda M, Inoue K.
  • Journal Title: Mol Pain. Volume: 10:53 Pages: 1-6
  • DOI: 10.1186/1744-8069-10-53
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans (2014)
  • Author(s): Kobayakawa K, Kumamaru H, Saiwai H, Kubota K, Ohkawa Y, Kishimoto J, Yokota K, Ideta R, Shiba K, Tozaki-Saitoh H, Inoue K, Iwamoto Y, Okada S
  • Journal Title: Science Translational Medicine Volume: 6 Issue: 256 Pages: 256-256
  • DOI: 10.1126/scitranslmed.3009430
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain. (2014)
  • Author(s): Masuda T, Iwamoto S, Yoshinaga R, Tozaki-Saitoh H, Nishiyama A, Mak TW, Tamura T, Tsuda M, Inoue K.
  • Journal Title: Nat Commun. Volume: 5 Issue: 1 Pages: 3771-3771
  • DOI: 10.1038/ncomms4771
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IRF8 is a transcriptional determinant for microglial motility. (2014)
  • Author(s): Masuda T, Nishimoto N, Tomiyama D, Matsuda T, Tozaki-Saitoh H, Tamura T, Kohsaka S, Tsuda M, Inoue K.
  • Journal Title: Purinergic Signal. Volume: 10（3） Issue: 3 Pages: 515-21
  • DOI: 10.1007/s11302-014-9413-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] C-C chemokine receptor type 5 is an important pathological regulator in the development and maintenance of neuropathic pain. (2014)
  • Author(s): K. Matsushita, C. Kojima, H. Tozaki-Saitoh, M. Tsuda, K. Inoue, S. Hoka.
  • Journal Title: Anesthesiology Volume: 印刷中 Issue: 6 Pages: 1491-503
  • DOI: 10.1097/aln.0000000000000190
  • Peer Reviewed / Open Access
• [Presentation] 侵害刺激時における脊髄アストロサイトシグナリングのin vivo imaging (2014)
  • Author(s): 松田 烈士、齊藤 秀俊、津田 誠、井上 和秀
  • Organizer: 第67回日本薬理学会西南部会
  • Place of Presentation: 北九州
  • Year and Date: 2014-11-23
• [Presentation] C-C chemokine receptor type 5 is an important pathological regulator in the development and maintenance of neuropathic pain (2014)
  • Author(s): Katsuyuki Matsushita, Chinami Kojima, Hidetoshi Tozaki-Saitoh, Makoto Tsuda, Sumio Hoka, Kazuhide Inoue
  • Organizer: 日本薬理学会
  • Place of Presentation: 仙台
• [Remarks] 九州大学薬学研究院薬理学分野
  • URL: http://yakkou.phar.kyushu-u.ac.jp/