Opioids as a new therapy for inflammatory arthritis: Immunopharmacological mechanisms

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Arthritis is a chronic inflammatory disorder characterized by joint pain, swelling and stiffness. In fact, 69% of patients present with radiographic erosions and joint space narrowing during the first three years of the disease and it is insufficiently appreciated that patients with rheumatoid arthritis may have a 5-year mortality similar to patients with cardiovascular or neoplastic disease. Prevention of disability and death is the ultimate goal of treatment. However, no cure is yet available. Instead, current treatment is aimed at relieving symptoms and improving functional performance. There is now a growing recognition that patients with rheumatoid arthritis require more agressive treatment early in the disease, before the development of erosions and deformity. My work has shown for the first time that opioid drugs that act via kappa (k) receptors in the periphery are able to ameliorate the incidence and severity of disease symptoms in rat adjuvant arthritis. Histological and radiological analysis reveals a significant, beneficial effect on joint pathology. The present proposal seeks to build upon this basic information gained in rats into the anti-inflammatory mechanisms of opioid action. I will now apply my expertise to extend this research in animals to human tissues. I am able to combine multiple techniques to carry out a systematic and rigorous study on human synovium from arthritis patients. This work aims to find out why opioids have anti-arthritic actions and might potentially lead to potent, less toxic and less expensive new therapies for arthritis and increase our understanding of the pathogenesis of arthritis.