Intra-articular injection of the selective cyclooxygenase-2 inhibitor meloxicam (Mobic) reduces experimental osteoarthritis and nociception in rats.

Abstract

OBJECTIVE:

To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes.

METHODS:

OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes.

RESULTS:

OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage.

CONCLUSIONS:

Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.

• Authors: Z-H Wen, C-C Tang, Y-C Chang, S-Y Huang, C-H Chen, S-C Wu, S-P Hsieh, C-S Hsieh, K-Y Wang, S-Y Lin, H-L Lee, C-H Lee, H-C Kuo, W-F Chen, Y-H Jean
• Journal: Osteoarthritis and cartilage (Osteoarthritis Cartilage) Vol. 21 Issue 12 Pg. 1976-86 (Dec 2013) ISSN: 1522-9653 [Electronic] England
• PMID: 24084190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Cyclooxygenase 2 Inhibitors
• Thiazines
• Thiazoles
• Extracellular Signal-Regulated MAP Kinases
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Meloxicam

Topics

• Animals
• Anterior Cruciate Ligament Injuries
• Arthritis, Experimental (drug therapy, enzymology, pathology)
• Cartilage, Articular (cytology, drug effects, pathology)
• Chondrocytes (drug effects, enzymology)
• Cyclooxygenase 2 Inhibitors (pharmacology, therapeutic use)
• Extracellular Signal-Regulated MAP Kinases (drug effects, metabolism)
• Injections, Intra-Articular
• JNK Mitogen-Activated Protein Kinases (drug effects, metabolism)
• Meloxicam
• Mitogen-Activated Protein Kinases (drug effects, metabolism)
• Nociception (drug effects)
• Osteoarthritis, Knee (drug therapy, enzymology, pathology)
• Rats
• Rats, Wistar
• Synovial Membrane (pathology)
• Thiazines (pharmacology, therapeutic use)
• Thiazoles (pharmacology, therapeutic use)
• p38 Mitogen-Activated Protein Kinases (drug effects, metabolism)