Date of Graduation
Eberly College of Arts and Sciences
Steven G Kinsey
Christina L Duncan
Miranda N Reed
Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory joint disease, affecting approximately 1% of the world population. This autoimmune disease is characterized by pain, stiffness, swelling, and breakdown of cartilage in synovial joints. Current RA analgesic treatments (i.e., pain reducing drugs) are ineffective or induce negative side effects, and so there are many concerted efforts to discover new RA treatments. Cannabinoids have analgesic and anti-inflammatory properties; however, the challenge remains to harness the medical potential of cannabinoids without inducing negative psychoactive effects (e.g., cognitive deficits, emotional disruption, and abuse potential). An alternative approach focuses on the endogenously produced cannabinoids (endocannabinoids). The endocannabinoids 2-arachidonoyl glycerol (2-AG) and anandamide are catabolized by the enzymes monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), respectively. Pharmacological inhibition of MAGL or FAAH increases brain levels of the respective endocannabinoids, 2-AG or anandamide, and significantly decreases inflammatory pain. The present study tested the hypothesis that MAGL inhibition decreases hyperalgesia, locomotor suppression, and allodynia caused by collagen-induced arthritis (CIA), a well-established animal model of inflammatory arthritis. Separate groups of mice subjected to CIA were administered acute or chronic doses of the selective MAGL inhibitor JZL184 and tested for (1) thermal hyperalgesia in the hotplate and tail immersion tests, (2) mechanical allodynia, and (3) suppressed locomotor activity. Thermal hyperalgesia was significantly attenuated by acute JZL184 (8 or 40 mg/kg) in the hot plate test, but not the tail immersion test. The lack of JZL184 attenuation of hyperalgesia in the tail immersion test may indicate a JZL184 supraspinal mechanism of action. Although the present study was hampered by ongoing model development, these results suggest that MAGL inhibition may be a promising strategy for the treatment of pain caused by inflammatory arthritis.
Nass, Sara R., "Analgesic and Anti-Inflammatory Effects of Monoacylglycerol Lipase Inhibition in Mice Subjected to Collagen-Induced Arthritis" (2015). Graduate Theses, Dissertations, and Problem Reports. 6297.