- Clinical Trials
- Research News
- Industry Trends
- Agency Actions
- Drug Safety Issues
- Approvals, Launches, & New Indications
- Health Care Reform
Researchers Find Molecular Mechanism Responsible for OA Pain
Discovery may lead to new approaches to pain control (Dec. 27)
Researchers at Rush University Medical Center, in collaboration with investigators at Northwestern University, have identified a molecular mechanism central to the development of osteoarthritis (OA) pain — a finding that could have major implications for future treatment of this often-debilitating condition.
“Clinically, scientists have focused on trying to understand how cartilage and joints degenerate in osteoarthritis. But no one knows why it hurts,” said study leader Anne-Marie Malfait, MD, PhD.
The new research was published in the Proceedings of the National Academy of Sciences.
Joint pain associated with OA has unique clinical features that provide an insight into the mechanisms that cause it, the researchers said. First, joint pain has a strong mechanical component: It is typically triggered by specific activities — for example, climbing stairs elicits knee pain — and is relieved by rest. As structural joint disease advances, pain may also occur in rest. Heightened sensitivity to pain, including mechanical allodynia (pain caused by a stimulus that does not normally evoke pain, such as lightly brushing the skin with a cotton swab), and reduced pain-pressure thresholds are features of OA.
Malfait and her colleagues examined the molecular pathways of OA pain in a surgical mouse model. The researchers assessed the development of pain-related behaviors and concomitant changes in dorsal root ganglia (DRG) — nerves that carry signals from sensory organs toward the brain. They found that a chemokine known as monocyte chemoattractant protein-1 (MCP-1) and its receptor, chemokine receptor 2 (CCR2), are central to the development of pain associated with knee OA.
MCP-1 regulates the migration and infiltration of monocytes into tissues, where they replenish infection-fighting macrophages. Previous research has shown that MCP-1 and CCR2 are central in pain development following nerve injury.
“Increased expression of both MCP-1 and its receptor CCR2 may mediate increased pain signaling through direct excitation of DRG neurons, as well as through attracting macrophages to the DRG,” the researchers said.
“This is an important contribution to the field of osteoarthritis research,” commented Dr. Joshua Jacobs, professor and chairman of orthopedic surgery at Rush University Medical Center. “Rather than looking at the cartilage breakdown pathway in osteoarthritis, Dr. Malfait and her colleagues are looking at the pain pathway, and this can take OA research into a novel direction that can lead to new pain remedies in the future.”
According to the Arthritis Foundation, an estimated 27 million Americans have OA. Treatment of the disease in the U.S. costs approximately $200 billion annually.
Source: Rush University Medical Center; December 27, 2012.