2018 Fiscal Year Final Research Report
Hypothalamo-neurohypophysial and hypothalamo-spinal nociceptive pathways in the arthritis using transgenic rats
| Project/Area Number |
16K10925
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
上田 陽一 産業医科大学, 医学部, 教授 (10232745)
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| Research Collaborator |
SUZUKI Hitoshi
OHNISHI Hideo
SAKAI Akinori
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 関節炎 / オキシトシン / バゾプレッシン / 視床下部―下垂体―副腎軸 / 脊髄後角 / c-Fos遺伝子 / TRPV |
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| Outline of Final Research Achievements |
We evaluated the neurological reaction in the hypothalamo-neurohypophysial and spinal pathway using the knee arthritis model. The neuronal activity in the hypothalamus, anterior pituitary (AP) and lumbar segments (L4) were examined. The neuronal activities of oxytocin (OXT) and vasopressin (AVP) cells in the hypothalamus, and the lamina I-II cells associated nociceptive modulation of the ipsilateral dorsal horn in the L4, and the cells in the AP associated stress modulation were increased in the arthritis rats. The synthesis of nociceptive and stress related hormones such as OXT and AVP, corticotropin-releasing hormone and proopiomelanocortin were increased simultaneously by arthritis. In addition, transient receptor potential vanilloid (TRPV) 1 and 4 knock out mice were used to observe the responses of spinal dorsal horn cells to nociceptive stress. The result suggested that the deletion of these genes associated the neuronal activation in the lamina III-IV cells.
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| Free Research Field |
整形外科学
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| Academic Significance and Societal Importance of the Research Achievements |
疼痛受容において、全身の疼痛反応に密接に関係していると考えられている中枢神経系の役割は不明な点が多い。本研究課題では、関節炎発症による疼痛モデルラットを用い、疼痛受容経路（視床下部－脊髄後角Ⅰ層およびⅡ層）に局在するニューロンの活性化を最初期遺伝子であるc-Fosを指標に可視化・定量評価し、侵害受容およびストレス関連ホルモンの合成が増加していることを明らかにした。また、TRPV1および4 に着目し、疼痛刺激により、これらの遺伝子欠損は脊髄後角I-II層だけでなく、III-IV層神経細胞活性化を促すことを確認した点は、疼痛治療のターゲットとして注目される可能性があり社会的意義があると考える。
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