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

我们研究了一种名为spinorphin（LVVYPWT）的神经肽的特性，该肽是一种来自牛脊髓的内源性肽，在抗炎和抗伤害活性中起作用。Spinorphin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，Spinorphin抑制BK反应的机制与镇痛剂吗啡不同。Spinorphin也在多形嗜中性粒细胞介导的炎症中发挥作用。为了阐明Spinorphin在炎症和疼痛控制中的作用，我们专注于类风湿性关节炎（RA）患者滑膜和脑脊液（CSF）蛋白质的变化，RA是一种以慢性和伤害性疼痛为特征的复杂自身免疫性疾病。最近，几种蛋白质如滑液中的S100 A8/A9（MRP 8/MRP 14）异源复合物（小钙结合蛋白）和血清中的II型胶原和热休克蛋白已被描述为RA-α ...更多信息 相关标记候选者。脑脊液（CSF）中的生物标志物，被认为是反映类风湿关节炎疼痛的信号，但是，很少被调查。在此，我们使用二维差异凝胶电泳（2D-DIGE）结合质谱（MS）和蛋白质印迹法（Western blotting）检测了CSF中RA的生物标志物，并与对照组或骨关节炎（OA）的生物标志物进行了比较。蛋白质斑点的表达在各组之间没有显著差异;然而，在RA组中观察到一些显著的变化：7例RA患者中有4例70-80 kD蛋白质的表达增加2倍或更多，而7例患者中有6例10-15 kD蛋白质的表达减少2倍或更多。通过串联MS分析各组之间的差异表达点。Western blotting揭示了一些具有几种抗体的蛋白质。这些结果表明，蛋白质可能是RA病理学的候选标记物。这些蛋白质的进一步鉴定以及它们的表达变化与病理学之间的关系正在进行中。少

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