Robust anti-nociceptive effects of monoacylglycerol 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. 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

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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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