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Breakthrough Study Reveals Potential for Non-Opioid Treatments for Osteoarthritis-Related Pain

A woman holds her knee and winces in pain.

Osteoarthritis affects more than 32 million people in the U.S., and the joint pain that comes with the disease can be excruciating.

For some Americans, managing severe osteoarthritis-related pain means taking opioid medications. Researchers have been looking for pain treatments that are not only more effective but can serve as an alternative to opioids. A new study by RUSH researchers, recently published in Nature Communications, may hold the key to new non-opioid related therapies.

According to the study — a collaboration between RUSH and Northwestern — a subset of sensory neurons that promote osteoarthritis-related joint pain and inflammation was discovered. This finding suggests that there is a new therapeutic target for managing pain.

Researchers worked off of previous findings regarding the ion channel protein Piezo2 and neurons known as nociceptors. Nociceptors are sensory nerves that respond to stimuli which produce pain. This can be seen in osteoarthritis when mechanical force impacts degraded joints. Studies have found that Piezo2 allows nociceptors to respond to mechanical force.

Knowing this, RUSH researchers set off to find if Piezo2 could hold the key to reducing joint pain.

“Osteoarthritis pain is often associated with daily activities, like walking and climbing stairs, that involve applying mechanical forces to our joints,” authors of the study, Anne-Marie Malfait, MD, PhD, The George W. Stuppy, MD, Chair of Arthritis, RUSH Medical College and Rachel E. Miller, PhD, associate professor, RUSH Medical College explain. “Piezo2 is a protein important for the ability of neurons to sense mechanical forces. Therefore, we hypothesized that targeting Piezo2 may be useful for alleviating osteoarthritis pain.”

Using Piezo2 knock-out mice, investigators found that osteoarthritis-related pain and inflammation were significantly reduced. They also found that female mice were protected from mechanical sensitization associated with inflammatory joint pain, and male mice were protected from the joint pain associated with osteoarthritis.

After a closer look at sensory neurons using single-cell RNA sequencing, investigators also found that Piezo2 is expressed by nociceptors that innervate joints in osteoarthritis in both mice and humans.

“We found that reducing the amount of Piezo2 expressed by nociceptors could reduce pain in mouse models of osteoarthritis and joint inflammation,” Malfait and Miller say.

These findings point to targeting Piezo2 as a new therapeutic treatment for osteoarthritis-related pain, which could serve as an effective alternative to therapies that include opioids.

“If we can design drugs that specifically target Piezo2, we may be able to treat joint pain in a safer and more effective manner than with currently available treatments,” Malfait and Miller say.


This work was supported by the Northwestern University NUSeq Core Facility, a Rheumatology Research Foundation Innovative Research Award, and National Institutes of Health grants R01AR077019, R01AR064251, R01AR060364, P30AR079206, P30AG10161, P30AG72975, R01AG15819, and R01AG17917.