17 Apr Understanding the Biomechanics of Osteoarthritis Pain
When osteoarthritis (OA) strikes, pain flashes to sensory receptors, unleashing tiny electrical pulses that race up the spinal cord to the brain. Neurons, or specialized nerve cells, release chemical messengers that deliver pain signals from arthritic joints to the sensory network.
Now a new generation of researchers is seeking answers to puzzling questions about osteoarthritis pain. With funding from the Arthritis National Research Foundation, Rachel Miller, PhD, an Assistant Professor in the Department of Internal Medicine at Rush University Medical Center, is investigating how mechanical stimuli trigger osteoarthritis pain.
Chronic pain affects over 100 million Americans and costs the country $500 billion a year in lost productivity. The debilitating pain of OA is a leading cause of disability worldwide. To date, there are no targeted therapies, just non-specific pain medications with potentially dangerous side effects.
Prescription opioids are effective in the short-term, but can lead to addiction and overdose. Aspirin raises the risk of bleeding, while anti-inflammatory drugs like naproxen and ibuprofen can cause liver, kidney and cardiovascular problems. Some OA patients try shots and nerve pain drugs, but still suffer severe and chronic osteoarthritis pain. When it comes to relieving the osteoarthritis pain, there are few good options.
Where does osteoarthritis pain come from? What’s really going on when your knee hurts? What’s the source of the nagging ache in your joints?
It’s difficult to design treatments for OA when researchers don’t understand which cell types—and which molecules on those cell types—sense mechanical stimuli and turn it into pain. Dr. Miller is looking at neurons and cartilage cells inside the knee that sense and respond to mechanical stimuli, yet the specific receptors that translate those signals remain unknown.
Although millions of people around the world suffer from osteoarthritis, there are few treatment options beyond total joint replacement. The chronic degenerative disease destroys cartilage and spurs overactive nerves to relay signals to the spinal cord in a cycle of unrelenting pain.
“Despite the fact that pain is the major symptom of osteoarthritis, the sources of pain associated with OA are still understudied,” explains Dr. Miller. “We don’t even know precisely where the nerves that sense pain signals and other types of touch signals are located within the joint. How disease changes nerve pathways also remains unclear.”
In her osteoarthritis research, Dr. Miller is exploring pain mechanisms, including changes in genetic expression and chemical messengers. She hopes to pinpoint how sensory neurons misfire to cause chronic pain.
“Everybody has sensory neurons that respond if you touch a hot stove,” she says. “When you are in chronic pain, just walking around is painful. We want to understand the complex process that occurs when cartilage degrades and signals the nerves to feel pain.”
She developed an imaging technique that allows her team to visualize what happens when researchers apply a pinch or a twist to the knee of a genetically modified mouse. “We can watch the neurons fire in real time,” she explains. “The images show that a particular type of neuron responds in OA, but not in a normal mouse.”
The goal is to find ways to directly target pain pathways. “I hope to discover how cells within the knee joint sense and respond to mechanical loading,” says Dr. Miller, who is using her engineering training to study the role of mechanical stimuli. “Understanding how cells respond to mechanical load normally — and how it changes in osteoarthritis — may someday lead to the development of new drugs to treat osteoarthritis.”
Dr. Miller’s reasons for studying osteoarthritis pain are both personal and professional. “A lot of my friends and family members have suffered from OA as they age,” she says. “It’s frustrating to see the decrease in their quality of life,” says Dr. Miller. “Receiving a grant from the ANRF at this early stage in my career is very important, since it helps me to establish myself as an independent researcher and will help to set the stage for future federal grant support as my research expands.”