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

我们研究了一种叫做spinorphin （LVVYPWT）的神经肽的特性，这是一种来源于牛脊髓的内源性肽，在抗炎和抗伤害活性中起作用。Spinorphin显著抑制小鼠缓激肽（BK）诱导的伤害性屈肌反应。值得注意的是，spinorphin抑制bk反应的机制不同于止痛剂吗啡。Spinorphin也在多形核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，我们重点研究了类风湿性关节炎（RA）患者滑膜和脑脊液（CSF）蛋白的变化。类风湿性关节炎是一种以慢性和痛觉性疼痛为特征的复杂自身免疫性疾病。最近，滑膜液中的S100A8/A9 （MRP8/MRP14）异复合体（小钙结合蛋白）、血清中的II型胶原蛋白和热休克蛋白等几种蛋白已被描述为RA-a -更多相关标志物候选物。然而，脑脊液（CSF）中的生物标志物，被认为反映类风湿性关节炎疼痛的信号，很少被研究。在这里，我们使用二维凝胶电泳（2D-DIGE）结合质谱（MS）和Western blotting检测脑脊液中RA的生物标志物，并将其与对照组或骨关节炎（OA）的生物标志物进行比较。3组间蛋白质水平差异超过2倍。各组间蛋白斑点的表达无显著差异；然而，在RA组中观察到一些明显的斑点表达变化：与对照组或OA组相比，7例RA患者中有4例70-80 kD蛋白增加了2倍或更多，而7例患者中有6例10-15 kD蛋白减少了2倍或更多。串联质谱Western blotting分析各组差异表达点，发现部分蛋白含有多种抗体。这些结果表明这些蛋白可能是RA病理的候选标记物。这些蛋白的进一步鉴定及其表达变化与病理之间的关系目前正在进行中。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