Chronic pain gene discovery may improve treatment

A single gene may play a major role in how we perceive pain, UK scientists have discovered. Research published in the journal Science, by a team from the University of Cambridge, shows that the HCN2 gene may be a vital target for future pharmacological research into pain relief.

This gene belongs to the HCN (hyperpolarization activated cyclic nucleotide) group of proteins, responsible for ferrying molecules across membranes in the cell. Despite the fact these ion channels have been known about for many years, they were not well understood. Since the HCN4 protein was known to control electrical impulses in the heart, it was thought that the HCN2 protein, expressed in pain-sensitive nerve endings, might play a role in controlling how electrical impulses in those nerves carry pain messages to the brain.

To test this, the researchers first grew nerve cells lacking HCN2 in the lab, to examine how they reacted to electrical stimuli, compared to cells with HCN2. Next, they moved onto mice lacking HCN2, and tested how quickly the mice reacted to pain.

Chronic pain can be neuropathic (lifelong ongoing pain, where nerves are damaged) or inflammatory (persistent injury such as a burn or arthritis, which results in sensitive nerve endings and increased pain sensation). Not only did the mice in the study suffer no neuropathic pain, even more encouraging was the fact that they still responded to acute pain, meaning they can still react to, and remove themselves from, situations that might be dangerous.

Professor Peter McNaughton, lead author of the study, said: 'Individuals suffering from neuropathic pain often have little or no respite because of the lack of effective medications. Our research lays the groundwork for the development of new drugs to treat chronic pain by blocking HCN2'.

Several million people in the UK — possibly as many as one in five — suffer from chronic pain, defined as pain lasting more than three to six months, occurring more than three times a week and causing severe discomfort. Some are affected by rare conditions such as the blood disorder erythromelalgia, others have more common causes like osteoarthritis.

Many experience depression and sleep deprivation, often leading to an inability to work. Chronic pain is believed to cost the UK economy approximately £5 billion a year.