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OBJECTIVE: OA is the most common joint disease, affecting 10-15% of people over 60 years of age. However, up to 40% of individuals with radiologic damage are asymptomatic. The purpose of this study was to assess the role of the endogenous opioid system in delaying the onset of pain in a murine model of osteoarthritis (OA). METHODS: Osteoarthritis was induced by transection of the medial meniscotibial ligament. Pain was assessed by monitoring weight distribution and activity. At various times postsurgery, the opioid receptor antagonists naloxone or peripherally restricted naloxone methiodide were administered, and pain was assessed. Levels of the micro-opioid receptor were assessed in the nerves innervating the joint by real-time reverse transcription-polymerase chain reaction analysis. RESULTS: As in human disease, significant joint damage occurred in mice before the onset of pain. To assess whether delayed pain was partly the result of increased endogenous opioid function, naloxone or naloxone methiodide was administered. Both opioid receptor antagonists led to pain onset 4 weeks earlier than in vehicle-treated mice, indicating a role of the peripheral opioid system in masking OA pain. The expression of the micro-opioid receptor in the peripheral nerves supplying the joint was transiently increased in naloxone-responsive mice. CONCLUSION: These findings indicate that a temporal induction of micro-opioid receptors in the early stages of OA delays the onset of pain. This is of clinical relevance and may contribute to the assessment of patients presenting with pain late in the disease. Furthermore, it may point to a mechanism by which the body blocks pain perception in moderate states of tissue damage, allowing an increased chance of survival.

Original publication




Journal article


Arthritis rheum

Publication Date





3110 - 3119


Animals, Arthritis, Experimental, Cartilage, Male, Mice, Opioid Peptides, Osteoarthritis, Knee, Pain, Receptors, Opioid, mu