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吻側延髄腹内側部に連絡する新経路が及ぼす口腔顔面慢性疼痛への役割

连接延髓头侧腹内侧的新通路对口面部慢性疼痛的作用

基本信息

批准号：
21K11256
负责人：
杉生真一
金额：
$ 2.66万
依托单位：
Osaka University of Human Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2021
资助国家：
日本
起止时间：
2021-04-01 至 2024-03-31
项目状态：
已结题

项目摘要

口腔顔面領域の一次中継核である三叉神経脊髄路核中間亜核（Vi）と尾側亜核（Vc）の移行部（Vi/Vc）と下行性疼痛調節を担う吻側延髄腹内側部：Rostral ventromedial medulla（RVM）に連絡するVi/VcのVc領域での役割を調べるために、三叉神経第3枝の下顎神経の枝である左側（L）下歯槽神経（IAN）を切断し、右側（R）IANは無処置の動物をCut群とし、またLのIANを無切断で露出のみ、RのIANは無処置の動物をSham群とした。手術2週後にCut群とSham群の動物動態をデジタルVon Freyテストにより、調べた結果、三叉神経第2枝の支配領域の口髭部皮膚領域での機械的疼痛逃避行動を引き起こす閾値（g）は、Sham群（L：16.5±3.9, R：14.0±2.5）を示し、Cut群（L：8.2±1.6, R：16.2±4.3）を示した。Cut群Lの閾値は、Sham群Lに比べ有意な減少を認めたことにより、Cut群を神経障害性疼痛のモデルとして確立した。これらの動物を使用し、三叉神経第2枝の中枢側のVcI/II層領域のFosとGABAの発現数について調べた結果、Cut群LのFosは、Sham群Lに比べ有意に増加した。これらの結果から、Cut群はSham群に比べ、VcI/II層領域での2次ニューロンの活動性が亢進していることが示された。一方Cut群LのGABAの発現は、Cut群R、Sham群LとSham群Rに比べ有意に減少した。これらの結果から、Cut群はSham群に比べ、VcI/IIでのGABA作動性抑制の欠如が示された。以上の結果から、口腔顔面領域における神経障害性疼痛時にGABAが減少したことで、VcI/II層の抑制の欠如が起こり、その結果Fosの発現（2次ニューロンの活性）を増加させ、神経障害性疼痛が生じている可能性が示唆された。

The primary medial nucleus of the oral-facial region (Vi), the transitional portion of the trigeminal spinal pathway nucleus (Vc), and the descending pain regulator (Vi/Vc) are located in the ventral medial portion of the rostral extension: Rostral ventromedial medla (RVM) is the third branch of the trigeminal nerve in the mandibular nerve. The left (L) inferior dentinal nerve (IAN) is Cut off. The right (R) IAN is not cut off. The animals in the RVM are cut off. The IAN in the L is not cut off. R's IAN has no disposal of animals. 2 weeks after surgery, the animal dynamics of Cut group and Sham group were measured by Von Frey test, and the mechanical pain avoidance behavior in the mandible skin area dominated by the second branch of trigeminal nerve was induced by threshold (g). Sham group (L: 16.5±3.9, R: 14.0±2.5) was measured by threshold (g). Cut group (L: 8.2±1.6, R: 16.2±4.3) was measured by threshold (g). The threshold value of Cut Group L is lower than that of Sham Group L. The threshold value of Cut Group L is lower than that of Sham Group L. The threshold value of Sham Group L is lower than that of Sham Group L. The threshold value of Cut Group L is lower than that of Sham Group L. The threshold value of Sham Group L is lower than that of Sham Group L. The threshold value of Cut Group L is lower than that of Sham Group L. The threshold value of Sham Group L is lower than that of Sham Group L. The threshold value of Cut Group L is lower than that of Sham Group L. The threshold value of Sham Group L is lower than that of Sham Group L. The threshold value of Sham Group L is lower than that of Sham Group L. The threshold value of Cut Group L is lower than that of Sham Group L. The threshold value of Sham Group L. The threshold value of Sham Group L is lower than that of Sham Group L. The threshold value of Sham Group L. The threshold value of Sham Group L is lower than that of Sham Group L. The number of Fos and GABA in the central VcI/II region of the second branch of the trigeminal nerve was adjusted. The number of Fos and GABA in the cut group L was increased intentionally. The result is that the Cut-off group is higher than the Sham group, and the activity of the Cut-off group is higher than that of the Sham group. The occurrence of GABA in Cut group L, Cut group R, Sham group L and Sham group R is intentionally reduced. The results showed that the ratio of Cut group to Sham group and VcI/II group to GABA action inhibition was insufficient. The above results showed that GABA decreased during neuropathic pain in the oral facial region, inhibition of VcI/II layer increased, and the occurrence of Fos (activity of 2 times neuropathic pain) increased, indicating the possibility of neuropathic pain occurring.