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Studies in a new pain control of spinorphin, an endogenous peptide, in rheumatoid arthritis

旋诺啡（一种内源性肽）在类风湿性关节炎中的新疼痛控制研究

基本信息

批准号：
16591577
负责人：
YAMAMOTO Yukio
金额：
$ 1.92万
依托单位：
Tokyo Metropolitan Organization for Medical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

We have studied the characterization of a neuropeptide called spinorphin (LVVYPWT), an endogenous peptide derived from bovine spinal cord, which plays a role in anti-inflammatory and anti-nociceptive activity. Spinorphin significantly inhibits bradykinin (BK)-induced nociceptive flexor responses in mice. Notably, the mechanism of the inhibition of BK-responses by spinorphin is different from that of morphine, an analgesic. Spinorphin also plays roles in polymorphonuclear neutrophils-mediated inflammation. To clarify the roles of spinorphin in inflammation and pain control, we focused on the changes that occur in the proteins of synovial and cerebrospinal fluids (CSF) of rheumatoid arthritis (RA) patients, a complex autoimmune disease characterized by chronic and nociceptive pain. Recently, several proteins such as the S100A8/A9 (MRP8/MRP14) heterocomplex (small calcium binding proteins) in synovial fluid, and collagen type II and heat shock protein in serum, have been described as RA-a … More ssociated marker candidates. Biomarkers in cerebrospinal fluid (CSF), considered to reflect signals of RA pain, have, however, scarcely been investigated. Here, we examined biomarkers of RA in CSF as compared with those of controls or of osteoarthritis (OA) using two-dimensional difference gel electrophoresis (2D-DIGE) together with mass spectrometry (MS) and Western blotting.Differences over 2-fold in the level of protein were compared among the 3 groups. The expression of the protein spots was not significantly different among the groups ; however, some notable changes in the expression of spots were observed in the RA group : 70-80 kD proteins increased 2-fold or more in 4 of 7 RA patients, while 10-15 kD proteins decreased 2-fold or more in 6 of 7 patients compared with those in the control or the OA group. Differentially expressed spots among the groups were analyzed by tandem MS. Western blotting revealed some proteins with several antibodies. These results indicate that the proteins may be marker candidates of RA pathology. Further identification of these proteins, and the relation between changes in their expression and pathology are now in progress. Less

我们研究了一种名为Spin的神经肽(LVVYPWT)的特性，它是一种来自牛脊髓的内源性多肽，具有抗炎和抗伤害性活性。Spinogin显著抑制缓激肽(BK)诱导的小鼠伤害性屈肌反应。值得注意的是，Spin抑制BK反应的机制与镇痛剂吗啡不同。Spinogin也在中性粒细胞介导的炎症中发挥作用。为了阐明Spin在炎症和疼痛控制中的作用，我们重点研究了类风湿关节炎(RA)患者滑液和脑脊液(CSF)中蛋白质的变化。RA是一种复杂的自身免疫性疾病，以慢性和伤害性疼痛为特征。最近，滑液中的S100A8/A9(mrp8/mrp14)异源复合体(小钙结合蛋白)、血清中的II型胶原和热休克蛋白等几种蛋白被描述为RA-a…。更多关联标记候选对象。脑脊液中的生物标志物被认为是反映类风湿关节炎疼痛的信号，然而，很少有人对其进行研究。在这里，我们用二维差示凝胶电泳法(2D-DGE)结合质谱仪(MS)和Western blotting检测脑脊液中RA的生物标志物，并与对照组或骨关节炎(OA)的生物标志物进行比较。各组间蛋白斑点表达差异无统计学意义，但类风湿关节炎组斑点蛋白表达有显著变化：7例RA患者中4例70-80kD蛋白表达增加2倍以上，6例10-15kD蛋白表达减少2倍或以上。两组间的差异表达斑点进行串联分析，Western blotting显示了一些带有几种抗体的蛋白质。这些结果表明，这些蛋白可能是类风湿关节炎病理的候选标记。对这些蛋白质的进一步鉴定以及它们的表达变化与病理之间的关系目前正在进行中。较少

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

新しい疼痛抑制物質spinorphinの疾病時における動態-関節リウマチ患者の脳脊髄液において-

类风湿性关节炎患者脑脊液中新型止痛药斯诺啡在患病期间的动态变化

DOI：
发表时间：
2005
期刊：
ペインクリニック 26(12)
影响因子：
0
作者：
田井重行;小原京子;遠田正治;山元行男;羽里忠彦
通讯作者：
羽里忠彦

A change of a new sharp pain resistant material, spinorphin, in cerebrospinal fluids with the rheumatoid arthritis patients.

类风湿性关节炎患者的脑脊液中出现了一种新的抗剧烈疼痛物质——旋啡肽。

DOI：
发表时间：
2005
期刊：
Pain Clinic 26(12)
影响因子：
0
作者：
Shigeyuki;T. et al.
通讯作者：
T. et al.

Levels of spinorphin in cerebrospinal fluid derived from patients with pain increase with decreasing dipeptidyl peptidase III.

来自疼痛患者的脑脊液中的旋诺啡水平随着二肽基肽酶 III 的减少而增加。

DOI：
发表时间：
2005
期刊：
Pain Research 20
影响因子：
0
作者：
Yamamoto;Y.;Sato;H.;Fukasaku;S.;Hiramatsu;K.;Tai;S.;Shimamura M.;Hazato;T.
通讯作者：
T.

Two-dimensional electrophoretic analysis of disease-associated proteins in human cerebrospinal fluid from patients with rheumatoid arthritis.

对类风湿性关节炎患者脑脊液中疾病相关蛋白进行二维电泳分析。

DOI：
发表时间：
2005
期刊：
J.Electrophoresis 49
影响因子：
0
作者：
Yamamoto;Y.;Akita;Y.;Tai;S.;Fukasaku;S.;Yamaguchi;T.;Oshizawa;T.;Yamaoka;K.;Shimamura;M.;Hazato;T.
通讯作者：
T.

Levels of spinorphin in cerebrospinal fluid derived from patients with pain increases with decreasing dipeptidyl peptidase III.

来自疼痛患者的脑脊液中的旋诺啡水平随着二肽基肽酶 III 的减少而增加。