The role of neuron-glia interaction in neuropathic pain

神经元-胶质细胞相互作用在神经病理性疼痛中的作用

• 批准号: 15209051
• 负责人: INOUE Kazuhide
• 金额: $ 23.71万
• 依托单位: KYUSHU UNIVERCITY (2004-2005)National Institute of Health Sciences (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15209051/
• 关键词: ATP; P2X4; microglia; BDNF; anion gradient; GABA; ATP受容体; 神経因性疼痛; p38; MAPキナーゼ; アロディニア; サイトカイン; 行動薬理学; 脊髄後角

In neuropathic pain animal models, spinal microglia become hypertrophic in their short and thick processes within the first 24 hrs after peripheral nerve injury. The time-course of microglial activation in the dorsal horn correlated with that of the development of tactile allodynia. Also we found that the microglia over-expressed P2X4 receptors and that P2X_4 stimulation of microglia is not only necessary for tactile allodynia, but is also sufficient to cause the allodynia (Nature 424,778-783,2003). Next we found that P2X_4 receptor activation is necessary to sustain the depolarizing shift in E_<anion> in rats with nerve injury, and that P2X4 stimulation evoked the release of BDNF from microglia. BDNF itself caused the depolarizing shift in E_<anion> in rat spinal neurons. Blocking the action of P2X4,BDNF caused the reduction of allodynia. These findings show that both the decrease in paw withdrawal threshold and the shift in E_<anion> in LI neurons caused by ATP-stimulated microglia through P2X_4 require BDNF-TrkB signaling and that the source of BDNF is the microglia themselves (Nature,438,1017-1021).

在神经病理性疼痛动物模型中，脊髓小胶质细胞在其短而厚的突起中在外周神经损伤后的前24小时内变得肥大。背角小胶质细胞激活的时间过程与触觉异常性疼痛的发展相关。我们还发现小胶质细胞过度表达P2 X4受体，并且小胶质细胞的P2X_4刺激不仅是触觉异常性疼痛所必需的，而且足以引起异常性疼痛（Nature 424，778 - 783，2003）。我们还发现，P2X_4受体激活是维持神经损伤大鼠E_1去极化的必要<anion>条件，刺激P2X_4受体可引起小胶质细胞BDNF的释放。BDNF本身可引起大鼠脊髓神经元E_1的去极化偏移<anion>。BDNF阻断P2 X4的作用，引起异常性疼痛的减轻。这些发现表明，<anion>由ATP刺激的小胶质细胞通过P2X_4引起的缩爪阈值的降低和LI神经元中E_1的偏移都需要BDNF-TrkB信号传导，并且BDNF的来源是小胶质细胞本身（Nature，438，1017-1021）。

项目成果

Structure-activity relationship of bile acids and bile acid analogs in regard to FXR activation

• DOI: 10.1194/jlr.m300215-jlr200
• 发表时间: 2004-01-01
• 期刊: JOURNAL OF LIPID RESEARCH
• 影响因子: 6.5
• 作者: Fujino, T;Une, M;Nishimaki-Mogami, T
• 通讯作者: Nishimaki-Mogami, T

Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis.

DNA 微阵列分析揭示了全反式视黄酸和 Am80 诱导的 HL-60 细胞分化过程中 PI3 激酶/Akt 途径的差异调节。

• 发表时间: 2004
• 期刊: Biochemical Pharmacology 68
• 作者: S.Ishida;Y.Shigemoto-Mogami;Y.Shinozaki;H.Kagechika;K.Shudo;S.Ozawa;J.Sawada;Y.Oh
• 通讯作者: Y.Oh

ATP受容体. 麻酔管理

ATP 受体麻醉管理。

• 发表时间: 2003
• 作者: Miura H;Kato H;Kusakabe Y;Ninomiya Y;Hino A;井上和秀
• 通讯作者: 井上和秀

T.Moriyama, T.Iida, K.Kobayashi, T.Higashi, T.Fukuoka, H.Tsumura, C.Leon, N.Suzuki, K.Inoue, C.Gachet, K.Noguchi, M.Tominaga: "Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated th

T.Moriyama、T.Iida、K.Kobayashi、T.Higashi、T.Fukuoka、H.Tsumura、C.Leon、N.Suzuki、K.Inoue、C.Gachet、K.Noguchi、M.Tominaga：“可能

P2×4 receptors induced in spinal microglia gate tactile allodynia after nerve injury.

神经损伤后脊髓小胶质细胞诱导的 P2×4 受体导致触觉异常性疼痛。

• 发表时间: 2003
• 期刊: Nature 424
• 作者: M.Tsuda;Y.Shigemoto-Mogami;S.Koizumi;A.Mizokoshi;S.Kohsaka;M.W.Salter;K.Inoue
• 通讯作者: K.Inoue