By Michelle Jaffee
For people with myotonic disorders, muscles have difficulty relaxing after contraction, leading to stiffness, falls and, for many, pain that can substantially affect quality of life. Now, new research in mice sheds light on mechanisms at play and, notably, suggests that a recently approved nonopioid drug might offer relief.
The preclinical results, published in The Journal of Clinical Investigation, point to the potential of targeted treatment for pain associated with this broad group of rare, inherited neuromuscular conditions.
“Myotonia is the inability of skeletal muscle to relax,” said lead author Tyler Nelson, Ph.D., a postdoctoral research assistant scientist in the lab of senior author Rajesh Khanna, Ph.D. “You can think of skeletal muscles as having ‘gas’ and a ‘brake.’ If you have myotonia, it’s due to either a broken brake or too much gas.”
For the new study, a research team from the University of Florida’s McKnight Brain Institute used mouse models to analyze the little-studied relationship between myotonic muscle dysfunction and pain-like behavior. Using behavioral testing and measurements of neural activity across peripheral sensory neurons, the spinal cord and the brain, they found that pain-like behavior and altered sensory processing can persist after overt muscle symptoms resolve.
The findings, researchers said, challenge a long-standing assumption that myotonia is purely a disorder of skeletal muscle by demonstrating that abnormal muscle activity can produce lasting changes in sensory processing.
Additionally, they tested suzetrigine, a nonopioid drug approved last year by the FDA that is first in a new class of pain-management medicines. Also called Journavx, the compound reduces acute pain by targeting Nav1.8, a sodium channel involved in pain signaling in the peripheral nervous system.
“Testing this drug, we were able to completely block pain-like behavior and sensitization, suggesting there might be an avenue for, first, how the pain might be caused, but then also there might be an actionable target to use,” Nelson said.
The next step, researchers said, is to investigate whether additional mechanisms are at play and whether the peripheral sensory abnormalities identified in mouse models carry over to human myotonia.
“We want to see the provenance of where the pain is coming from, but that is not just limited to the periphery,” said Khanna, director of UF’s Center for Advanced Pain Therapeutics and Research. “Pain is in the brain. So is there a pathway that’s activating the brain that we can also go after?”