Although p38 inhibitors have been studied extensively in animal models of inflammatory arthritis, there is little work in models of osteoarthritis. In the present study we have shown that the p38 inhibitors SB203580 and VX ARQ 197 745 inhibit Gelenkverschlei in an animal model of osteoarthritis are analgesics in a model of inflammatory pain. The inhibitory effect of p38 inhibitors on Gelenkverschlei iodoacetate in the model in this study is the size order of a studied the inhibitory effect of MMP inhibitors in this model. Although the effects of the p38 inhibitor in OA model was previously not an inhibitor of interleukin converting enzyme pralnacasan reported shown Gelenkzerst Tion reduce in a surgically-induced model and a model of spontaneous nozzles osteoarthritis in M Have the advantages of the inhibition of cytokines shown.
Likewise, reducing the intraarticular Re injection of IL 1RA development Knorpell Emissions and expression of metalloproteinases in the canine model of osteoarthritis. These experiments show that some inflammatory mediators affected by p38 play an r In cartilage degeneration in a number AZD1480 of different animal models of osteoarthritis observed important. However, it is difficult to translate these effects observed in animal models of human clinical benefit in osteoarthritis because it is currently. No approved disease-modifying medicines for the treatment of osteoarthritis Including a number of protein kinases, Were Lich MAPK has been implicated in the induction and maintenance of pain sensitization.
P38 is tr in spinal microglia activation # adds to the development and maintenance of neuropathic pain by inducing the synthesis of inflammatory cytokines and other molecules neuroscience. The administration of the p38 inhibitor SB203580 prevents intrathecal spinal nerve ligation-induced mechanical allodynia. P38 inhibitor R 130 823 has been reported to have an analgesic effect of chronic pain in adjuvant arthritis model in rats. This effect, the bradykinin B1 receptor has been shown as p38, that mediate hyperalgesia the bradykinin B1 receptor in adjuvant-induced arthritis. These data support the use of inhibition of p38 directly affect the pain of osteoarthritis. The introduction of the biological treatment of rheumatoid arthritis And other inflammatory diseases is a large en therapeutic progress.
These proteins Generally bind cytokines, specific lines of cell surface Surface receptors, or proteins that modulate the costimulatory signals. Although very effective, biological agents have some disadvantages: K N drugs can target a single cytokine or cellular Ren receptor, in complex diseases such as RA, the number of patients who respond N must Restrict agents nken administered No drugs by injection are very expensive compared to traditional medicines. Obtained as a result Ht as orally bioavailable small molecules Target key intracellular Re signaling molecules have attracted attention because they can regulate the production of cytokines and cytokine action. The multiplicity m Glicher goals is challenging, but kinase inhibitors represent a particularly interesting approach. Among these are the mitogen-activated protein kinase Were the subject of many drug development programs because of their r In the regulation of cytokines, chemokines.