Epilepsy drug may help minimize joint damage, pain

The current study focused on a way to slow the joint damage caused by osteoarthritis rather than focusing on pain relief alone. Researchers noted that osteoarthritis involves cartilage breakdown and pain. At the cellular level, this involves chondrocytes, or cartilage cells and neurons, which are involved in the pain response from osteoarthritis.

Researchers were particularly interested in understanding the presence and work of voltage-gated sodium channels in the cartilage cells. These sodium channels are a specific type of protein found in cell types.

To start, researchers examined chondrocytes in people with osteoarthritis. They found that the Na_v1.7 sodium channels are present in chondrocytes and that the amount is increased in osteoarthritis.

Using mouse models, researchers genetically deleted Na_v1.7 and studied the results. They found that in dorsal root ganglia neurons, the junction boxes for nerves as they exit the spinal column, this deletion contributed to pain reduction. In the chondrocyte cells in mice, the deletion contributed to much less structural damage and progression of osteoarthritis and less pain-related behavior from the osteoarthritis.

The results concluded that inhibiting these channels could be the key to slowing osteoarthritis progression and minimizing pain. Researchers looked at several components to test this hypothesis and some of the underlying mechanisms involved.

Dr. Yoon noted the following:

“The study investigating Na_v1.7 is important to create disease modifying medicines for osteoarthritis. Understanding the cellular mechanisms underlying osteoarthritis and creating targeted therapies to address both pain and the actual disease itself will be necessary to modify the impact of this disease.”

One key area of interest is that the researchers were then able to test if the drug Carbamazepine affected osteoarthritis progression in mice. Carbamazepine inhibits Na_v1.7 channels, and doctors use it in the treatment of conditions like epilepsy and bipolar disorder.

They found that the Carbamazepine helped with pain and lowered amounts of cartilage loss.

Study author Chuan-Ju Liu, PhD, Charles W. Ohse Professor and Translational Orthopaedic Lab Director in the Department of Orthopaedics at Yale University School of Medicine, explained the key findings of the research to Medical News Today:

“Our discovery of the sodium channel Na_v1.7 as a target for both pain relief and disease modification represents a significant stride towards a novel therapeutic strategy to slow down or prevent osteoarthritis progression while concurrently alleviating associated pain. Inhibiting Na_v1.7 channels with specific inhibitors has shown promising results in slowing joint damage across various animal models of osteoarthritis. Expanding on this, our investigations with the non-specific Na_v-blocking drug, Carbamazepine, also demonstrated a robust protective effect against joint degeneration in mouse osteoarthritis models.”

While this research is promising, it also has certain limitations. The main limitation is that the findings are derived from mouse models. Researchers also only included cell samples from a limited number of patients, which could have influenced the study’s findings. Experts must be cautious and do more research before seeing how this data applies to people with osteoarthritis.

Dr. Liu noted the following areas of continued research:

“There is still a long way to go in translating current findings from animal models to human applications. We need to understand why a low number of sodium channels has such significant effects on chondrocyte biology. Additionally, further testing is essential to explore the comparative effects of various sodium channel inhibitors on chondrocytes, cartilage, and different osteoarthritis models.”

“Our next steps involve assessing new therapeutic strategies focused on blocking Na_v1.7 channels and exploring gene therapy approaches to reduce the production of these channels. This research aims to bridge the gap between animal models and human treatments, bringing us closer to a future where osteoarthritis is more manageable, enabling patients to lead healthier and happier lives.”
— Dr. Chuan-Ju Liu, study author

Osteoarthritis is a common subtype of arthritis. When people have osteoarthritis, there is breakdown and damage in the joints, leading to pain, swelling, and movement struggles. Osteoarthritis affects various joints and can range in severity.

Study author Dr. Liu said there were challenges with treating osteoarthritis.

“Osteoarthritis, the most common form of arthritis, affects over [7.6%] of the global population and is a leading cause of disability. Unfortunately, there’s currently no cure, and existing treatments mainly focus on relieving pain without addressing the underlying cartilage breakdown. Patients often resort to invasive surgeries like total knee or hip replacements,” he told Medical News Today.

There are certain things people can do that may help to minimize their risk of developing osteoarthritis, such as maintaining a healthy body weight and exercising regularly.

Management of osteoarthritis involves a number of strategies, often to help with symptom relief. There is growing evidence of the effectiveness of a range of exercises for knee osteoarthritis, including aerobic exercise, strength training, and balance training. A range of medications can relieve pain, and people may also try injections of corticosteroids or hot and cold therapy. However, it can be difficult to find effective strategies that prevent disease progression.

Dr. Steve Yoon, a board certified physiatrist and director of The Regenerative Sports and Joint Clinic at Cedars-Sinai Kerlan-Jobe Institute in Los Angeles, who was not involved in the study, explained that common treatments for osteoarthritis “require a multidisciplinary approach.”

Managing osteoarthritis

“Modalities such as ice and heat can be used topically. Topical creams and ointments used may include anesthetic and anti-inflammatory medications as well as cannabidiol (CBD). Oral medications including acetaminophen and ibuprofen may be used for more serious pain control. Physical therapy will include a strength and low impact exercise program.”
— Dr. Steve Yoon