Funded by Deanship of Scientific Research
Amount: 46000 JD
Osteoarthritis is slowly progressive disease characterized by destruction of articular cartilage (Goldring et al., 2009), subchondral bone sclerosis (Burr et al., 2012), and chronic inflammation of the synovium (Chen et al., 2014). Symptoms usually manifest as pain, stiffness, swelling and crepitus (Dieppe et al., 2005). Currently, analgesic treatments for osteoarthritis have limited efficacy (Bjordal et al., 2007) and accompanied by gastrointestinal and cardiovascular side effects.
Cannabinoids are a group of compounds structurally related to Δ9-tetrahydrocannabinol (Δ9-THC), a substance found in the Cannabis sativa plant which has been used for centuries for its psychoactive and medicinal effects (Adams et al., 1996). Considering the physiological role of cannabinoid receptors (CB1 And CB2) in controlling multiple responses including pain and inflammation (Guindon et al., 2009), cannabinoids exert analgesic effects in rodent models of osteoarthritis (Yao et al., 2008). However, previous studies have shown that cannabinoids and cannabinoid like-compounds could produce analgesia in a CB1/CB2 independent fashion by interaction with other receptors such as The transient receptor potential vanilloid (TRPV1) (Akopian et al., 2009) and peroxisome proliferator-activated receptors (PPARs) (LoVerme et al., 2005).
PPARs are nuclear receptors activated by fatty acids, eicosanoids and synthetic agonists. Three PPAR isoforms have been identified—α, β/δ, and γ (Berger et al., 2005; Michalik et al., 2006). PPARs are involved in controlling lipid metabolism (Willson et al., 2005), inflammatory and immune responses (Daynes and Jones, 2002). Several studies have confirmed the ability of PPAR ligands to inhibit the signaling pathways of joint inflammation and reduce the formation of cartilage catabolic factors (Fahmi et al., 2001). Yet, the analgesic properties of PPAR ligands in osteoarthritis are less clear. In this study, rat models of osteoarthritis and molecular biology techniques will be used to investigate the possible role of PPAR receptors in mediating the analgesic effects of different cannabinoids such as WIN-55,212-2, HU210 and cannabinoid-like compounds such as Palmitoylethanolamide (PEA) and Oleoylethanolamine (OEA).