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Novel Opioid Provides Less Addictive Pain Relief and May Slow Osteoarthritis Progression

ADDICTIVE opioids are routinely taken by many people with arthritis to manage their pain. Kappa opioid receptor (KOR) agonists are known to be less addictive and now a study from Keck Medicine, University of Southern California, Los Angeles, California, USA has shown that a locally administered kappa opioid may slow progression of osteoarthritis (OA), in addition to easing pain.

Alleviation of pain with KOR agonists is a more targeted approach than commonly prescribed opioids, with some opioids that selectively activate KOR not able to cross the blood–brain barrier and, therefore, induce substance dependency. Instead, these KOR agonists act locally at the site of injury and hence have a reduced risk of addiction, a common and serious problem with nonselective opioids.

In the in vitro aspect of the study, primary human articular cartilage and synovial tissue samples were obtained from patients with knee OA undergoing total joint replacement, as well as from healthy controls. In human OA articular chondrocyte, the selective peptide activated the KOR and induced significant inhibition of hedgehog signalling, which is involved in the degeneration of cartilage, compared to the nontreated chondrocytes (p=0.002). A partial medial meniscectomy model of knee OA in rats was used in the in vivo aspect of the study. The novel agonist maintained cartilage content, structure, and functional properties, and reduced osteophyte formation by 70% (p=0.005, versus vehicle-treated controls).

Lead author Dr Alexander Weber commented: “The implications of this study may someday alter how we provide orthopaedic care to significantly reduce the number of patients experiencing long-term pain and addiction.” Corresponding author Dr Denis Evseenko added: “We hope that the findings of our study will lay the foundations for clinical research to further current understandings of the relationship between kappa opioids and osteoarthritis in humans to improve clinical care and quality of life.”