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

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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