Chronic arthritis pain and the disappointment of u-opioid therapy

Nearly one third of the world's adult population suffers with the pain of arthritis. While NSAIDs and COX-2 inhibitors offer the promise of relief, these drugs also bring the risk of adverse effects, from stomach ulcers to heart attack. Recent studies have suggested the potential of tapping into the body's supply of painkilling peptides as a safe, natural approach to arthritis pain management. Extraneous substances such as morphine can be disadvantageous in arthritis pain therapy due to a large number of adverse side-effects associated with these compounds. In addition, the lack of selectivity of morphine means that precise targeting of u-opioid receptors to control chronic pain has proven to be problematic. What's more, several clinical and experimental studies of m-opioid therapy have shown ambiguous results. The recent discovery of a natural morphine-like compound in joints called endomorphin 1 could circumvent these therapeutic drawbacks due to its greater selectivity for the u-opioid receptor. Endomorphin 1 has the potential, therefore, to be a major painkilling agent in the body with less chance of risk.

Researchers at the University of Calgary set out to determine the effectiveness of endomorphin 1, with a painkilling capacity equal to or greater than morphine – on knee joint pain. Their subjects were male rats with induced arthritis, both acute and chronic. Their findings, featured in the October 2005 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), shed light on why u-opioid therapy may not work to control long-term arthritis pain.

Previous research into u-opioid therapy for arthritis has primarily focused on changes occurring in the hours immediately following tissue inflammation. This study is the first to examine the impact on chronic inflammation. The rat models were randomly assigned to the different treatment groups: acute (48-hour) inflammation, chronic (1-week and 3-week) inflammation, and normal controls. Under anesthesia, endomorphin 1 was injected into the arthritic knee joints of all affected rats. Therapeutic effectiveness was assessed by measures of joint edema formation and sensory nerve activity associated with pain.

In rats with acute arthritis, endomorphin 1 worked to significantly reduce the hypersensitivity of joint nerves by as much as 75 percent. In the rats with chronic arthritis, however, endomorphin 1 had no observable effect on the telltale triggers of pain. On the strength of these findings, researchers concluded that chronic inflammation negates the pain-relieving benefits of the body's u-opioid receptors.

"These observations highlight a possible inadequacy of the endogenous opioid system to alleviate chronic arthritis pain," notes study author Dr. Jason McDougall. By offering clear insights into the disappointment of u-opioid therapy, this study suggests the need for rethinking the best use of endomorphin 1 and redirecting pain management research toward more promising alternatives for long-term arthritis sufferers.

Article: "Chronic Arthritis Down-Regulates Peripheral u-Opioid Receptor Expression With Concomitant Loss of Endomorphin 1 Antinociception," Zongming Li, David Proud, Chunfen Zhang, Shahina Wiehler, and Jason J. McDougall, Arthritis & Rheumatism, October 2005; 52:10; pp. 3210-3219.

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