| Autor: |
Holly T. Philpott, Jason J. McDougall |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Arthritis Research & Therapy, Vol 22, Iss 1, Pp 1-9 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1478-6362 |
| DOI: |
10.1186/s13075-020-2096-3 |
| Popis: |
Abstract Background Endocannabinoids are showing great promise as effective mediators for controlling joint inflammation and pain. One strategy that could be harnessed to promote endogenous cannabinoid function is to inhibit the enzymatic break down of endocannabinoids locally in the joint. KML29 is an inhibitor of monoacylglycerol lipase (MAGL) activity which has been shown to promote increased 2-arachodonylglycerol (2-AG) levels in the circulation and in peripheral tissues. It is also known that 2-AG can be metabolised via the cyclo-oxygenase-2 (COX-2) pathway leading to the production of pro-inflammatory prostaglandins, which may counteract the effects of 2-AG. Therefore, this study examined the effect of KML29 alone as well as in combination with low-dose celecoxib (CXB) on joint pain and inflammation in the monoiodoacetate (MIA) model of osteoarthritis (OA) pain. Methods Injection of MIA (3 mg) into the knee joints of male Wistar rats was used to model OA pain, inflammation, and nerve damage. Pain behaviour was assessed by von Frey hair algesiometry, and inflammation was evaluated using intravital microscopy to measure leukocyte trafficking in the synovial microvasculature. Results Intra-articular injection of MIA produced mechanical hypersensitivity as measured by von Frey hair algesiometry. Local injection of KML29 (700 μg) reduced joint pain at day 14 post-MIA induction, and this analgesic effect was blocked by the cannabinoid receptor antagonists AM281 and AM630 (P |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full text from SpringerLink