Peripheral neuropathy is a debilitating condition for which there are few effective treatments, mainly because we do not fully understand the underlying molecular mechanisms, say researchers whose latest discovery appears to shed new light in this area.

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In diabetic neuropathy – one of the most common forms of peripheral neuropathy – pain can start in the feet then progress up the legs.

The team, from McGill University in Montreal, Canada, reports the discovery in The Journal of Neuroscience. They hope the findings will lead to new research to help patients suffering from peripheral neuropathy or neuropathic pain.

According to the National Institutes of Health, around 20 million people in the US have some form of peripheral neuropathy – trauma or disease damage to the peripheral nervous system that causes weakness, numbness or pain. It can affect people with diabetes, cancer, multiple sclerosis and many other conditions.

The peripheral nervous system is the vast network of nerve fibers that sends signals between the central nervous system (the brain and spinal cord) and every other part of the body.

In peripheral neuropathy, the damaged nerve fibers have a heightened response to normal signals and send incorrect messages to pain centers in the brain – a process known as “peripheral and central sensitization.”

The chronic pain condition can present in various forms and follow different patterns. For example, in one of the most common, diabetic neuropathy, nerve damage occurs in an ascending pattern. Pain and numbness often are felt symmetrically in both feet followed by a gradual progression up both legs.

The new discovery surrounds the activity of a part of the brain called the anterior cingulate cortex (ACC), thought to be the region most consistently involved in pain processing.

Senior author Philippe Séguéla, a professor in the department of neurology and neurosurgery, and colleagues discovered new information about a type of channel that controls the transmission of pain signals to the ACC.

From lab tests on rats, they found that blocking these channels – called hyperpolarization-activated cyclic nucleotide-gated (HCN) channels – reduced over-stimulation of the ACC and dramatically decreased feelings of pain.

“Our study has revealed one important mechanism linking chronic pain to abnormal activity of the ACC and it provides a cellular and molecular explanation for the overstimulation of neurons in the prefrontal cortex,” says Prof. Séguéla. “This gives us new perspectives on therapeutic strategies that could target the HCN channels to help relieve chronic pain.”

More recently, using brain scans of the prefrontal regions of the brain, researchers have also discovered that emotional, psychological and cognitive factors can influence pain perception in neuropathic pain.

Prof. Séguéla explains these have shown that the ACC is important for cognitive functions linked to memory, feelings and emotions, and we already know that patients who suffer chronic pain have problems with working memory and focusing on tasks, and they may also suffer from depression and anxiety. He concludes:

Our findings open new doors to research possible treatment of these debilitating symptoms that are linked to chronic pain.”

The discovery follows another study Medical News Today reported in July 2015, where a team from the University of California-Davis suggests a biological process called endoplasmic reticulum stress is a significant driver of neuropathic pain. An expert who was not involved in the study said it offers new opportunities for drugs or drug combinations to treat chronic pain.