Ricerc@Sapienza

Rheumatoid arthritis (RA) is a chronic and systemic autoimmune inflammatory disease associated with pain, synovial hyperplasia, cartilage destruction and functional disability in most patients. A lot of different pathways participates in the pathogenesis of RA. Specifically, pro-inflammatory cytokines, including tumor necrosis factor-alfa (TNF-¿), interleukin-1 beta (IL-1ß) and IL-6 play key roles in RA.
PK2 is a new chemokine that acting on two G-protein linked receptors, prokineticin receptor 1 and 2 (PKR1 and PKR2), modulates the nociceptive threshold and is involved in immuno-inflammatory processes. We have already demonstrated that the prokineticin system (PK) plays a role in animal models of inflammatory and neuropathic pain and we also demonstrated that the pharmacological blockade of this system not only relieves pain, but also ameliorates the pathological processes underlying pain. Moreover, recently the involvement of PK2 and PKR2 in the pathogenesis of type II collagen-induced arthritis in mice was reported. These data suggest that blocking PKRs might be a winning strategy in controlling of arthritic pain and pathology development.
Based on these considerations, the project aims to evaluate the role of the PK2/PKRs in the type II collagen (CII)-induced arthritis (CIA) and whether therapeutic treatment with a non-peptide PKR antagonist, PC1, might be useful in controlling arthritic pain and possibly the pathological processes underlying pain.