The Effects of Endocannabinoid Modulation and Neurogenic Inflammation in Experimental Knee Joint Arthritis
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Arthritis is a debilitating condition, and a leading cause of disability worldwide. Despite the prevalence of arthritis, few therapies are satisfactorily efficacious, and many are limited by serious adverse effects. It is for these reasons that the development of newer, safer and more efficacious arthritis therapies is essential. The knee is the second largest joint in the human body, and is one of the most affected joints in osteoarthritis. Furthermore, the knee is easily accessible in mice, making it an ideal joint for inducing experimental arthritis in rodents. Local neurogenic inflammation is mediated by the release of neuropeptides from the peripheral terminals of nociceptive fibres. Neurogenic inflammation has been implicated in a number of inflammatory conditions, including arthritis; therefore, understanding how neurogenic inflammation contributes to joint inflammation may help in the development of novel arthritis therapeutics. One family of molecules that shows tremendous promise for the management of arthritic inflammation and pain are the cannabinoids. These compounds were first identified in the Cannabis plant, but subsequent research has identified an endogenous cannabinoid system, that plays a role in both health and disease. One method that is used to increase endocannabinoid activity is inhibiting the enzymes responsible for their degradation. Using a drug called URB597, we can block fatty acid amide hydrolase, increasing articular endocannabinoids. The aim of this thesis was to investigate the contribution of neurogenic inflammation in experimental knee joint disease, as well as the therapeutic potential of the endocannabinoid system in joint inflammation and the development of arthritic pain.