Findings of a new study suggest that pain is not merely a symptom of arthritis but rather a cause of the condition.
The researchers, from the University of Rochester School of Medicine and Dentistry and the University of Torino, Italy, said new treatments may seek to interrupt “crosstalk” between joints and the spinal cord, according to a press release from the University of Rochester.
More specifically, the study, which appears in the October issue of Arthritis & Rheumatism, suggested that pain signals originating in arthritic joints — and the biochemical processing of those signals as they reach the spinal cord — worsen and expand arthritis. Researchers reported that nerve pathways carrying pain signals transfer inflammation from arthritic joints to the spine and back again, causing disease at both ends, according to the press release.
Co-investigator Stephanos Kyrkanides, PhD, DDS, said the current study provides strong evidence that two-way, nociceptive crosstalk may first enable joint arthritis to transmit inflammation into the spinal cord and brain and then to spread through the central nervous system from one joint to another.
Armed with the results, researchers have identified likely drug targets that could interfere with key inflammatory receptors on sensory nerve cells as a new way to treat osteoarthritis (OA).
“Until relatively recently, osteoarthritis was believed to be due solely to wear and tear — an inevitable part of aging,” Kyrkanides said in the press release. “Recent studies have revealed, however, that specific biochemical changes contribute to the disease, changes that might be reversed by precision-designed drugs. Our study provides the first solid proof that some of those changes are related to pain processing, and suggests the mechanisms behind the effect.”
Kyrkanides’ work centers around one such pro-inflammatory signaling chemical called Interleukin 1-beta (IL-1ß), which helps to ramp up the body’s attack on an infection.
The researchers genetically engineered a mouse where they could, on command, ramp up the production of IL-1ß in the jaw joint, a common site of arthritis. The experiments showed for the first time that turning up IL-1ß in a peripheral joint in mice caused higher levels of IL-1ß to be produced in the dorsal horns of the spinal cord, too, he said in the press release.
Using a second, even more elaborately engineered mouse model, the team also demonstrated for the first time that creating higher levels of IL-1ß in cells called astrocytes in the spinal cord caused more OA symptoms in joints.
“Our study results confirm that joints can export inflammation in the form of higher IL-1ß along sensory nerve pathways to the spinal cord, and that higher IL-1ß inflammation in the spinal cord is sufficient in itself to create OA in peripheral joints,” Kyrkanides said in the press release. “We believe this to be a vitally important process contributing to orthopedic and neurological diseases in which inflammation is a factor.”
For more information:
- Fiorentino PM, Tallents RH, Miller JH, et al. Spinal Interleukin-1ß in a mouse model of arthritis and joint pain. Arthr & Rheum. 58:3100-3109.