Study finds link between genetic markers and neuropathic pain

Neuropathic pain is a serious clinical condition caused by damage to the nervous system. It often feels like a burning, shooting, tingling, icy or stabbing sensation. Conditions such as diabetes or nerve damage can cause neuropathic pain, which is often long-lasting and has a major impact on quality of life. It is difficult to treat because the underlying factors and mechanisms are unknown. Currently, there are no effective treatments for this devastating condition as the clinical presentation varies from person to person.

Researchers from the University of Bergen, Lund University and Oxford University, together with colleagues from the European DOLORISK consortium, conducted the largest multicenter cohort of people to date, characterizing in detail different clinical presentations and subtypes of pain and used genetic studies to unravel the pain. their molecular roots. The findings are published in the news Pain.

Valeriya Lyssenko, professor of medicine at the University of Bergen and Lund University, and David Bennett, professor of neurology and neurobiology at the University of Oxford, said: “The entire consortium is pleased to confirm previously proposed new genetic markers of neuropathic pain and Turning off the excitability of sensory neurons via potassium channels (KCNT2) in neurons may be a way to reduce pain, including mechanical pain sensitivity. This is the first time this gene has been linked to pain in humans.

Low insulin levels, depression and alcohol

The genetic signals were especially clear in patients with diabetes. Importantly, the genetic analyzes suggested that clinical factors such as low insulin levels, depression and alcohol use disorders were causally related to neuropathic pain. This highlights the importance of measuring insulin secretion and assessing mental health in people with diabetes as factors associated with the severity of neuropathic pain.

Although further validation is needed in a large cohort of patients with diabetes, the results demonstrate that the contribution of sensory neurons to persistent pain is due to the desensitization of opioid receptors (OPRM1) and the hyperactivity of sodium channels (SCN9A) that transport sodium ions. in the cells plays a role in transmitting sensitivity to pain. People with a genetic variant in opioid receptors may need higher doses of painkillers to treat pain.

Interestingly, one of the sodium channel gain-of-function variants (SCN9a) has been shown to originate from Neanderthals, demonstrating how ancient ancestors may influence pain in the present day.