Effects of neonatal pain on developing neuronal networks

• Project/Area Number: 18K08854
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Kobe University
• Principal Investigator: Nomura Yuki 神戸大学, 医学研究科, 助教 (60643955)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 若年期疼痛 / ミクログリア / c-Fos / 炎症性疼痛 / 新生児 / 疼痛 / グリア細胞 / 神経細胞 / 行動異常 / 脳発達

Outline of Final Research Achievements

This study suggests that painful stimuli given in childhood induces hyperactive behavior later in life. Immunohistochemical analysis of c-Fos expression in the mature brain revealed neural activation in the cerebral cortex and piriform cortex. It suggests that neuronal activation in the amygdala-piriform cortex transition region might be associated with stress hormone responses (Nature 532;103, 2016), and that childhood pain stimulation might induce the changes to the stress response.S ince it was difficult to isolate glial cells from small brain regions where c-Fos expression was observed, we analyzed gene expression of markers of activation, cytokines, and chemokines in microglia isolated from a wider range of cerebral cortex or spinal cord. There was not significant difference in gene expression between the control and pain-stimulated groups. Isolation from local tissues and comprehensive gene analysis will be necessary in the future.

Academic Significance and Societal Importance of the Research Achievements

幼児期の疼痛刺激およびストレスは、神経発達や精神発達において有害事象を伴うことが明らかにされているが、その分子機構については不明な点が多い。本研究によって若年期の疼痛刺激が成熟期に多動性行動を示す可能性が示唆された。また、分子メカニズムの特定には至らなかったものの、梨状皮質をはじめとした、ストレス応答に関与する脳領域の神経活動の変化が認められたことから、ストレス耐性の脆弱化による行動変化が生じていた可能性が示唆される。今後は、神経活動の動態変化を含めた解析を加えることで、若年期の疼痛刺激による長期的な影響の分子メカニズムを解明する一助となる。

Research Products

• [Journal Article] Pain induces stable, active microcircuits in the somatosensory cortex that provide a new therapeutic target. (2021)
  • Author(s): Okada T, Kato D, Nomura Y, Obata N, Quan X, Morinaga A, Yano H, Guo Z, Aoyama Y, Tachibana Y, Moorhouse AJ, Matoba O, Takiguchi T, Mizobuchi S and Wake H
  • Journal Title: Sci Adv Volume: 7 Issue: 12 Pages: 8261-8261
  • DOI: 10.1126/sciadv.abd8261
  • Peer Reviewed / Open Access / Int'l Joint Research