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Expression of matrix metalloproteinases and components of the endocannabinoid system in the knee joint are associated with biphasic pain progression in a rat model of osteoarthritis

Authors Pajak A, Kostrzewa M, Malek N, Korostynski M, Starowicz K

Received 18 January 2017

Accepted for publication 10 May 2017

Published 21 August 2017 Volume 2017:10 Pages 1973—1989

DOI https://doi.org/10.2147/JPR.S132682

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Katherine Hanlon

Agnieszka Pajak, Magdalena Kostrzewa, Natalia Malek, Michal Korostynski, Katarzyna Starowicz

Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

Abstract: Matrix metalloproteinases (MMPs) are considered important in articular cartilage breakdown during osteoarthritis (OA). Similarly, the endocannabinoid system (ECS) is implicated in joint function and modulation of nociceptive processing. Functional interplay between ECS and MMPs has been recently indicated. Here, we tested if changes in the expression of selected MMPs and major ECS elements temporally correlate with the intensity of OA-related pain. Knee OA was induced in male Wistar rats by intra-articular sodium monoiodoacetate injection. OA-like pain behavior was tested using the dynamic weight bearing. Joint tissue samples at different time points after OA induction were subjected to gene (quantitative polymerase chain reaction) and protein (Western blot) expression analyses. Monoiodoacetate-induced nocifensive responses in rats showed a biphasic progression pattern. The alterations in expression of selected MMPs elegantly corresponded to the two-stage development of OA pain. The most substantial changes in the expression of the ECS system were revealed at a later stage of OA progression. Alterations within ECS are involved in the process of adaptation to persistent painful stimuli. The accumulation of MMPs in osteoarthritic cartilage may have a role in the biphasic progression of OA-related pain. Temporal association of changes in ECS and MMPs expression shows a potential therapeutic approach that utilizes the concept of combining indirect ECS-mediated MMP inhibition and ECS modulation of pain transduction.

Keywords: osteoarthritis, monoiodoacetate, pain, matrix metalloproteinases, endocannabinoid system

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