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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia
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Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia

机译：氧化亚油酸代谢产物激活脊髓TRPV1有助于炎性痛觉过敏

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摘要

Transient receptor potential vanilloid 1 (TRPV1) plays a major role in hyperalgesia and allodynia and is expressed both in the peripheral and central nervous systems (CNS). However, few studies have evaluated mechanisms by which CNS TRPV1 mediates hyperalgesia and allodynia after injury. We hypothesized that activation of spinal cord systems releases endogenous TRPV1 agonists that evoke the development of mechanical allodynia by this receptor. Using in vitro superfusion, the depolarization of spinal cord triggered the release of oxidized linoleic acid metabolites, such as 9-hydroxyoctadecadienoic acid (9-HODE) that potently activated spinal TRPV1, leading to the development of mechanical allodynia. Subsequent calcium imaging and electrophysiology studies demonstrated that synthetic oxidized linoleic acid metabolites, including 9-HODE, 13-HODE, and 9 and 13-oxoODE, comprise a family of endogenous TRPV1 agonists. In vivo studies demonstrated that intrathecal application of these oxidized linoleic acid metabolites rapidly evokes mechanical allodynia. Finally, intrathecal neutralization of 9- and 13-HODE by antibodies blocks CFA-evoked mechanical allodynia. These data collectively reveal a mechanism by which an endogenous family of lipids activates TRPV1 in the spinal cord, leading to the development of inflammatory hyperalgesia. These findings may integrate many pain disorders and provide an approach for developing analgesic drugs.
机译：瞬态受体电位香草酸1（TRPV1）在痛觉过敏和异常性疼痛中起主要作用，并在周围和中枢神经系统（CNS）中表达。但是，很少有研究评估中枢神经系统TRPV1介导损伤后痛觉过敏和异常性疼痛的机制。我们假设脊髓系统的激活释放了内源性TRPV1激动剂，该激动剂引起了该受体对机械性异常性疼痛的发展。使用体外灌注，脊髓的去极化触发了氧化亚油酸代谢产物的释放，例如有效激活脊髓TRPV1的9-羟基十八碳二烯酸（9-HODE），导致了机械性异常性疼痛的发展。随后的钙成像和电生理研究表明，合成的氧化亚油酸代谢物（包括9-HODE，13-HODE以及9和13-氧代ODE）组成了内源TRPV1激动剂家族。体内研究表明鞘内应用这些氧化的亚油酸代谢产物会迅速引起机械性异常性疼痛。最后，抗体在鞘内中和9-和13-HODE可以阻断CFA诱发的机械性异常性疼痛。这些数据共同揭示了内源性脂质家族激活脊髓中TRPV1的机制，从而导致炎症性痛觉过敏的发展。这些发现可能整合了许多疼痛疾病，并为开发止痛药提供了一种方法。

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    Amol M. Patwardhan; Phoebe E. Scotland; Armen N. Akopian; Kenneth M. Hargreaves;

  • 作者单位

    Departments of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229;

    Departments of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229;

    Departments of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229;

    Departments of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 Departments of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    inflammation; pain;

    机译：炎;痛;

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