European researchers have mapped the most comprehensive phenotyping of neuropathic pain and identified genetic markers associated with this serious condition. The new findings could be especially important for diabetes-patients.

Neuropathic pain is a severe clinical condition caused by damage to the nervous system. It often feels like a burning, shooting, tingling ice or stabbing sensation. Conditions such as diabetes or nerve injury 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 because the clinical presentation varies from person to person.

Researchers from the University of Bergen, Lund University and the University of Oxford, together with colleagues from the European DOLORISK consortium conducted the largest multicentre cohort of people to date, characterising different clinical presentations and subtypes of pain in detail, and using genetic studies to unravel their molecular roots.

Specific gene linked to human 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, comment:

“The entire consortium is delighted to confirm previously suggested and discover novel genetic markers of neuropathic pain. Switching 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 that this gene has been linked to pain in humans”.

Low insulin levels, depression and alcohol

The genetic signals were particularly apparent in patients with diabetes. Importantly, the genetic analyses suggested that clinical factors such as low insulin levels, depression and alcohol use disorder were causally linked to neuropathic pain. This highlights the importance of measuring insulin secretion and assessing mental health in people with diabetes as factors linked to 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 insensitivity of opioid receptors (OPRM1) and the hyperactivity of sodium channels (SCN9A) that transport sodium ions into the cells plays a role in transmitting sensitivity to pain. People with a genetic variant in opioid receptors may need higher doses of painkillers for the treatment of pain.

Interestingly, one of the gain-of-function variants in the sodium channel (SCN9a) has been shown to be derived from Neanderthals demonstrating how ancient ancestry can impact on pain in the present day.

Link to the study: https://journals.lww.com/pain/fulltext/9900/genetic_associations_of_neuropathic_pain_and.756.aspx

Prof. Valeriya Lyssenko: valeriya.lyssenko@uib.no
Prof. David Bennett: david.bennett@ndcn.ox.ac.uk