Roles of a rachidonic acid cascade in radicular pain induced by herniated nucleus pulposus in the rat

花生四烯酸级联在大鼠髓核突出引起的根性疼痛中的作用

• 批准号: 10671377
• 负责人: KAWAKAMI Mamoru
• 金额: $ 2.05万
• 依托单位: Wakayama Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671377/
• 关键词: nucleus pulposus; inflammation; nerve root; hyperalgesia; leukocyte; thromboxane; leukotriene; cyclooxygenase-2; radiculopathy; pain; disc herniation; leukocytopenia

It has been shown that autologous nucleus pulposus relocated on the lumbar nerve root in rats produces time dependent and reversible mechanical hyperalgesia which is thought to be an pain related behavior in peripheral neuropathic pain models. The purpose of this study were to examine the roles of leukocyte and biologically active substances including in the arachidonic acid cascade in pathophysiological mechanisms of radicular pain induced by the herniated nucleus pulposus. In rats with nitorgen mustard induced lekocytopenia, the nucleus pulposus produced neither mechanical hyperalgesia nor abundant inflammatory cells. Neuropathic pain produced by the nucleus pulposus, when placed on the nerve root, may be related to inflammatory cell infiltration induced by relocation of the nerve root, may be related to inflammatory cell infiltration induced by relocation of the nucleus pulposus rather than the nucleus pulposus it self. Biologically active substances such as prostaglandins, thrombox … More anes, leukotriences, and cyclooxygenase-2 (COX-2) which are metabolites involved in the arachidonic a acid cascade, are detected in herniated disc samples obtained from patients with lumbar disc herniation. Thromboxane AィイD22ィエD2 (TXAィイD22ィエD2) synthase inhibitor, leukotriene BィイD24ィエD2 (LTBィイD24ィエD2) receptor antagonist and COX-2 inhibitor, which were injected into the epidural space, resulted in decrease of mechanical hyperalgesia 3 and 7 days after epidural injection. Inflammatory reactions and granulation tissue were less pronounced 7 days after the epidural injection. It is possible that TXAィイD22ィエD2 LTBィイD24ィエD2 and COX-2, which are produced in the inflammatory cells around the nerve root, play a significant role in mechanical hyperalgesia induced by application of nucleus pulposus on the nerve root in the rat. Epidural injection of LTBィイD24ィエD2 receptor antagonist, TXAィイD22ィエD2 synthase inhibitor and/or COX-2 inhibitor may be therapeutically useful, and may attenuate painful radiculopathy due to lumbar disc herniation. Less

已经表明，在大鼠腰神经根上重新定位的自体髓核会产生时间依赖性和可逆的机械痛觉过敏，这被认为是周围神经性疼痛模型中的疼痛相关行为。本研究的目的是探讨白细胞和生物活性物质（包括花生四烯酸级联）在髓核突出引起的根性疼痛的病理生理机制中的作用。在氮芥诱导的白细胞减少症大鼠中，髓核既不产生机械性痛觉过敏，也不产生丰富的炎症细胞。髓核置于神经根时产生的神经性疼痛，可能与神经根移位引起的炎性细胞浸润有关，可能与髓核移位引起的炎性细胞浸润有关，而不是与髓核本身有关。从腰椎间盘突出症患者获得的椎间盘突出样品中检测到生物活性物质，如前列腺素、血栓素、白三烯和环氧合酶-2 (COX-2)，它们是参与花生四烯酸级联的代谢物。将血栓素 AィイD22ィエD2 (TXAィイD22ィエD2) 合成酶抑制剂、白三烯 BィイD24ィエD2 (LTBィイD24ィエD2) 受体拮抗剂和 COX-2 抑制剂注射到硬膜外腔，导致第 3 天和第 7 天机械性痛觉过敏减少硬膜外注射后。硬膜外注射后 7 天，炎症反应和肉芽组织不太明显。神经根周围炎症细胞产生的TXAィイD22ィエD2、LTBィイD24ィエD2和COX-2可能在大鼠神经根应用髓核引起的机械性痛觉过敏中发挥重要作用。硬膜外注射LTBィイD24ィエD2受体拮抗剂、TXAィイD22ィエD2合酶抑制剂和/或COX-2抑制剂可能具有治疗作用，并且可以减轻腰椎间盘突出引起的疼痛性神经根病。较少的

项目成果

Mamoru Kawakami, et al: "Messenger RNA expression of interleukins, phospholipase A2 and nitric oxide synthase in the nerve root and dorsal root ganglion induced by autologous nucleus pulposus in the rat"J Orthopaedic Research. 17. 941-946 (1999)

Mamoru Kawakami 等人：“大鼠自体髓核诱导的神经根和背根神经节中白细胞介素、磷脂酶 A2 和一氧化氮合酶的信使 RNA 表达”J Orthopaedic Research。

Kawakami M, et al: "The role of leukocytes in radicular pain secondary to lumbar disc herniation"SIROT99. 679-684 (1999)

Kawakami M 等人：“白细胞在腰椎间盘突出继发的神经根性疼痛中的作用”SIROT99。

Mamoru Kawakami: "Possible mechanism of painful radiculopathy in lumbar disc herniation." Clinical Orthopaedics and Related Research. 351. 241-251 (1998)

Mamoru Kawakami：“腰椎间盘突出症中疼痛性神经根病的可能机制。”

Mamoru Kawakami, Tetsuya Tamaki, Takuji Matsumoto, Koichi Kuribayashi, Toru Takenaka, Masahiro Shinozaki: "Role of leukocytes in radicular pain secondary to herniated nucleus pulposus."Clinical Orthopedics and Related research. (in press). (2000)

Mamoru Kawakami、Tetsuya Tamaki、Takuji Matsumoto、Koichi Kuribayashi、Toru Takenaka、Masahiro Shinozaki：“白细胞在髓核突出继发性根性疼痛中的作用。”临床骨科及相关研究。

Mamoru Kawakami, Tetsuya Tamaki, Takuji Matsumoto, Koichi Kuribayashi, Toru Takenaka, Masahiro shinozaki: "The role of leukocytes in radicular pain secondary to lumbar disc herniation."SIROT 99, Edited by H Stein, Se-II Suk, Ping-Chung Leung, K-G Thorngre

Mamoru Kawakami、Tetsuya Tamaki、Takuji Matsumoto、Koichi Kuribayashi、Toru Takenaka、Masahiro shinozaki：“白细胞在腰椎间盘突出症继发性根性疼痛中的作用。”SIROT 99，由 H Stein、Se-II Suk、Ping-Chung Leung 编辑