Investigation of Phyto-, Endo-, and Syntheto-cannabinoids in the Management of Osteoarthritis Pain and Inflammation in Rats

Abstract

The most prevalent form of joint disease, osteoarthritis (OA), is characterised by joint destruction, pain, and intermittent inflammation. It has recently emerged that OA is also associated with damage to the sensory nerves innervating these joints which leads to vasomotor dysfunction and neuropathic pain. Chronic pain associated with OA is the number one reason for patients to visit their physician, and is thought to be linked to neuropathy, inflammation and the degenerative changes that occur within OA joints. The ineffectiveness of currently used analgesics in providing symptom relief for OA patients suggests the need for novel therapeutic discoveries to help those affected by this disease. Cannabinoids are a family of molecules that have been widely shown to decrease pain and inflammation and show promise in combatting OA-associated pain and inflammation. These compounds were first isolated from the Cannabis sativa plant, and similar compounds have since been identified within our bodies. This endocannabinoid system is the body’s natural pain-modulating system and has been shown to be upregulated within the joints of OA patients. Targeted activation of the endocannabinoid system via locally-delivered compounds into the joint may help to enhance analgesia and reduce inflammation, while minimising the production of psychoactive side-effects traditionally associated with systemic cannabinoid use. The aim of this thesis was to investigate the therapeutic potential of a phytocannabinoid, an endocannabinoid, and a synthetocannabinoid, administered locally into the knee, to manage OA inflammation and pain.