Robust anti-nociceptive effects of MAG lipase inhibition in a model of osteoarthritis pain

Burston, James J.; Mapp, Paul I.; Sarmad, Sarir; Barrett, David A.; Niphakis, Micah J.; Cravatt, Benjamin F.; Walsh, David A.; Chapman, Victoria

Abstract

BACKGROUND AND PURPOSE: Chronic pain is often a symptom of knee osteoarthritis (OA) for which current analgesics are either inadequate, or are associated with serious side effects. The endocannabinoid system may offer alternative targets for pain-relief. We evaluated the effects of a potent and selective MAG lipase inhibitor (MJN110) on OA pain behaviour, spinal mechanisms of action and joint histopathology in the rat.
Experimental approach: Intra-articular injection of monosodium iodoacetate (MIA) models OA pain and mimics clinical joint pathology. Effects of MJN110 on MIA-induced weight bearing asymmetry and lowered paw withdrawal thresholds (PWTs), changes in spinal gene expression and brain levels of relevant lipids were determined.
Key results: Acute MJN110 (5 mg·kg−1) significantly reversed MIA induced weight bearing asymmetry (MIA /vehicle: 68 ± 6g; MIA /MJN110: 35 ± 4g, p

Citation

Burston, J. J., Mapp, P. I., Sarmad, S., Barrett, D. A., Niphakis, M. J., Cravatt, B. F., …Chapman, V. (2016). Robust anti-nociceptive effects of MAG lipase inhibition in a model of osteoarthritis pain. British Journal of Pharmacology, 173(21), 3134-3144. https://doi.org/10.1111/bph.13574

• Journal Article Type: Article
• Acceptance Date: Jul 22, 2016
• Online Publication Date: Aug 7, 2016
• Publication Date: Oct 10, 2016
• Deposit Date: Sep 20, 2016
• Publicly Available Date: Sep 20, 2016
• Journal: British Journal of Pharmacology
• Print ISSN: 0007-1188
• Electronic ISSN: 1476-5381
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 173
• Issue: 21
• Pages: 3134-3144
• DOI: https://doi.org/10.1111/bph.13574
• Public URL: https://nottingham-repository.worktribe.com/output/824035
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1111/bph.13574/abstract