A $3.6 million award from the National Institutes of Health will allow neurosurgical, neurology and neuroscience researchers at The Ohio State University Wexner Medical Center and College of Medicine to test a novel diagnosis and treatment combination for painful diabetic neuropathy. The approach combines spinal cord stimulation with measurement of small fiber nerve activity using a patent-pending device called Detecting Early Neuropathy (DEN).
Diabetes is a growing health concern worldwide, and rates are particularly high in the United States, with more than 37 million Americans – or about 1 in 10 – living with the disease, according to the Centers for Disease Control and Prevention. Diabetes is associated with numerous health problems, including peripheral neuropathy, which can lead to severe pain.
Peripheral neuropathy is the death of the nerve endings that innervate our tissues and organs, which can worsen the control of diabetes by blunting neural communication between the brain and peripheral tissues and organs. It's estimated that more than 30 million Americans suffer from peripheral neuropathy.
Options to diagnose and treat peripheral neuropathy are very limited and ineffective, and thus more research is needed to develop and test new options that can reduce the pain, discomfort, high medical costs and loss of productivity for patients. Patients have very few options for treatment of their debilitating peripheral neuropathy, and there's an over-reliance on addictive opioid pain medications which are only partially effective."
Kristy Townsend, PhD, co-principal investigator, associate professor in the Department of Neurosurgery at Ohio State
With peripheral neuropathy, typically multiple nerve types – sensory, sympathetic or motor – degenerate, so the symptoms are complex and can include numbness, tingling, burning, pain, and motor loss. In severe cases, patients may undergo limb amputation.
It is estimated that up to 70% of patients with diabetes will develop neuropathy, some even in the pre-diabetes state. Other small fiber neuropathies are caused by chemotherapy, aging, and now - long COVID, said Townsend, whose research program investigates nervous system plasticity, remodeling, and regeneration in situations of metabolic disease, such as obesity, diabetes, aging, cardiometabolic disease, and peripheral neuropathy.
"Spinal cord stimulation (SCS) is a cutting-edge therapy that provides device-mediated electrical stimulation to the spinal cord and has strong prior data demonstrating its efficacy in relieving chronic pain, including in patients with painful diabetic neuropathy," said co-principal investigator Brian Dalm, MD, a neurosurgeon and clinical assistant professor of neurological surgery at Ohio State Wexner Medical Center. Dalm specializes in neuromodulation, including deep brain stimulation, spinal cord stimulation and peripheral nerve stimulation.
The DEN is undergoing research and development by Townsend and colleagues through an academic spin-out company, Neuright Inc. The DEN was developed to more sensitively, functionally, and qualitatively measure and diagnose small fiber neuropathy so that the condition can be detected more easily, and earlier in the disease progression when therapies are likely to be more effective.
Together, this research collaboration allows synergistic clinical and translational data collection to investigate clinical outcomes and cellular mechanisms underlying the therapeutic effects of SCS for patients with painful diabetic neuropathy.
"While SCS holds great promise for patients with painful diabetic neuropathy, the mechanisms by which it works are unknown. We hypothesized that the effects include increased vascularization and release of nerve growth factors that could spur small fiber axon regeneration, and this newly funded R01 will be the first study to measure those outcomes in patients receiving SCS versus conventional medical management," Dalm said.
DEN measurements combined with tissue analyses will, for the first time, determine if SCS increases beneficial nerve regeneration as a contributor to pain relief.
Currently, there are no effective treatments to regenerate or regrow nerve endings lost to this condition, despite the knowledge that peripheral nerves uniquely and readily regenerate after other damage, such as injury by nerve crush.
"This could be a revolutionary finding, providing evidence that a non-pharmacological approach is effective at promoting neuropathy reversal," Townsend said.