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A new class of pain relievers that targets musculoskeletal pain receptors, instead of more general pain pathways, could alleviate osteoarthritis pain better than any drug now on the market, but hurdles remain before it’s approved by the U.S. Food and Drug Administration. Research on the new therapy was published yesterday in the New England Journal of Medicine.

Osteoarthritis occurs when joint cartilage wears down, with the worst cases requiring joint replacement surgery. The pain can be unrelenting, and there’s no real cure. Patients often get through the day by relying on pain relievers, typically starting with over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. As the pain intensifies and people become inured to the drugs’ effects, they gradually work their way up to opioids such as oxycodone.

The new treatment, called tanezumab, acts on a completely different pathway. While NSAIDs inhibit an enzyme that produces inflammation, and opioids target specific receptors in the central nervous system, tanezumab homes in on musculoskeletal pain receptors. This approach promises fewer side effects, such as internal bleeding, liver damage, and the danger of addiction, which can accompany the alternatives.

Tanezumab, which was developed by Pfizer, is the first in a new class of pain relievers that inhibit sensory neurons, preventing them from transmitting pain signals to the brain. In a clinical trial to assess the intravenous medicine’s efficacy, patients on tanezumab experienced as much as a 62 percent reduction in pain–as much as 40 percent better than the placebo.

“Nothing out there works like this–this is a game-changing molecule,” says Nancy Lane, director of the Center for Healthy Aging at the University of California, Davis, and the study’s lead researcher. NSAIDs and opiates show about half the efficacy of tanezumab (although the current study only compared different tanezumab doses to a placebo rather than to currently available medications). Still, Lane says, “The efficacy was beyond belief.”

Tanezumab works by preventing a protein called nerve growth factor from attaching to sensory neurons, thereby stopping the neurons from transmitting pain signals to the brain. It’s a pathway specifically related to muscle and bone pain, and therefore provides an opportunity for targeted pain relief.

“This really represents a new class of drugs, and it’s been many decades since we’ve introduced a new class of agents for treating osteoarthritis,” says Patrick Mantyh, a professor of pharmacology at the University of Arizona. “It’s an outstanding paper, very thorough, and a beautiful case of coming up with a really novel approach for treating pain and showing a clinically significant result.”

The Centers for Disease Control and Prevention conservatively estimates that about 27 million people in the U.S. suffer from osteoarthritis–a number that represents a huge opportunity for any company that can improve upon existing pain relief. At least four American pharmaceutical companies have therapies in development that inhibit either nerve growth factor or the receptor to which it binds; all are intensely watching Pfizer’s progress.

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Credit: Courtesy of Nevit Dilmen/Wikimedia Commons

Tagged: Biomedicine, drugs, neurons, pain, arthritis, chronic pain, osteoarthritis

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