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

Burston, James J. and Mapp, Paul I. and Sarmad, Sarir and Barrett, David A. and Niphakis, Micah J. and Cravatt, Benjamin F. and Walsh, David A. and Chapman, Victoria (2016) Robust anti-nociceptive effects of monoacylglycerol lipase inhibition in a model of osteoarthritis pain. British Journal of Pharmacology, 173 (21). pp. 3134-3144. ISSN 0007-1188

Full content URL: http://doi.org/10.1111/bph.13574

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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. xpression of MPGES1 (p < 0.05) in the ipsilateral dorsal horn of the spinal cord of MIA rats, compared to vehicle treated MIA rats. Both doses of MJN110 significantly elevated brain levels of the endocannabinoid 2-AG. Conclusions and implications: Our data support the further investigation of the therapeutic potential of MAG lipase inhibitors for the treatment of OA pain.

Additional Information:PMCID: PMC5056226
Keywords:2?arachidonoylglycerol (2-AG), membrane?associated PGE synthase?1 (mPGES1), glial fibrillary acidic protein (GFAP), Osteoarthritis (OA)
Subjects:B Subjects allied to Medicine > B140 Neuroscience
Divisions:College of Science > School of Chemistry
ID Code:31312
Deposited On:13 Mar 2018 08:46

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