Potential pain-releasing action of PAF antagonists in neuropathic pain animal models and the mechanisms of action

PAF拮抗剂在神经病理性疼痛动物模型中的潜在止痛作用及其作用机制

• 批准号: 21592421
• 负责人: MOTOYAMA Naoyo
• 金额: $ 2.91万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592421/
• 关键词: 保存修復学; 歯痛; アロディニア; 神経障害性疼痛; 難治性疼痛; 歯髄; 鎮痛

The present study elucidated the effectiveness of platelet-activating factor (PAF) antagonists against neuropathic pain in several different models of peripheral nerve injury and inserted them into the mechanism of anti-allodynia action. PAF antagonists by intravenous and oral administration have potent anti-allodynia action in mice with several different models of neuropathies. Also, PAF antagonists have potent anti-inflammatory and analgesic action in mice inflammatory pain models. Those effects were achieved with low doses and long lasting. Intrathecal injection of the PAF antagonists and siRNA against PAF receptor ameliorated allodynia. Together, these results suggest that PAF aggravates peripheral and spinal pronociceptive inflammatory responses and contributes to the pathogenesis of inflammatory and neuropathic pain. Regulation of PAF/PAF receptor system may be targets for future innovations for pathological pain management.

本研究阐明了血小板活化因子（PAF）拮抗剂在几种不同的周围神经损伤模型中对抗神经性疼痛的有效性，并将其纳入抗异常性疼痛作用机制中。PAF拮抗剂通过静脉内和口服给药在具有几种不同神经病模型的小鼠中具有有效的抗异常性疼痛作用。PAF拮抗剂在小鼠炎性疼痛模型中也具有较强的抗炎镇痛作用。这些效果是通过低剂量和长期持续来实现的。鞘内注射PAF拮抗剂和针对PAF受体的siRNA可改善异常性疼痛。总之，这些结果表明，PAF加剧外周和脊髓的疼痛性炎症反应，并有助于炎症和神经病理性疼痛的发病机制。PAF/PAF受体系统的调节可能是未来病理性疼痛管理创新的目标。

项目成果

Anti-allodynia Effects of Glycine Transporter inhibitors in Neuropathic Pain Models

甘氨酸转运蛋白抑制剂在神经病理性疼痛模型中的抗异常疼痛作用

• 发表时间: 2010
• 作者: Motoyama N ;Morita K;Kitayama T;Nishimura F;Kanemastu T;Dohi T
• 通讯作者: Dohi T

Mechanisms of phase-dependent pain-relief activity of glycine transporter inhibitors after nerve injury

神经损伤后甘氨酸转运蛋白抑制剂的相位依赖性镇痛活性机制

• 发表时间: 2010
• 作者: Morita K;Motoyama N;Kitayama T;Jinnin Y;Nishimura F;Kanemastu T;Dohi T
• 通讯作者: Dohi T

Mechanisms of phase-dependent pain-relief activity of glycine transporter inhibitors after nerve injury.

神经损伤后甘氨酸转运蛋白抑制剂的阶段依赖性疼痛缓解活性机制。

• 发表时间: 2010
• 作者: Morita K;Motoyama N;Kitayama T;Jinnin Y;Nishimura F;Kanemastu T;Dohi T
• 通讯作者: Dohi T

Mechanisms of phase-dependent pain-relief activity of glycine transp orter inhibitors after nerve injury; in MEDIMOND-Monduzzi Editore Internationa l Proceeding Division, 3rd Internationa l Congress on Neuropathic Pain NeuPSIG, Athens (Greece), 2010. Inte

神经损伤后甘氨酸转运蛋白抑制剂的阶段依赖性镇痛活性机制

• 发表时间: 2010
• 作者: Morita K;Motoyama N;Kitayama T;Kanemastu T;Dohi T
• 通讯作者: Dohi T

女性の痛み;性ホルモンによる疼痛制御

女性疼痛通过性激素控制；

• 发表时间: 2011
• 作者: 本山直世;森田克也;柏典子;本山智得;西村英紀
• 通讯作者: 西村英紀