Possible Breakthrough in Research about Chronic Pain Gene

Possible Breakthrough in Research about Chronic Pain Gene

Finding Could Lead to New Drugs that Block Chronic Pain


The HCN2 gene plays a significant, but not clearly understood role in regulating chronic pain.


A group of scientists has identified the role of the HCN2 gene in regulating chronic pain. Researchers from Cambridge University in England and the University of Cadiz in Spain recently published their findings in the journal Science. Their study uncovers a new understanding of the HCN2 gene and opens up the possibility of fighting chronic pain by developing drugs that block the gene’s protein production.

56 million people in the U.S. suffer from chronic pain, according to the National Institutes of Health. Chronic pain can be classified into two categories, inflammatory and neuropathic.

Inflammatory pain, such as burns and arthritis, occurs when a persistent injury causes the nerve endings to become more sensitive, thereby increasing pain sensation.

Neuropathic pain is caused by nerve damage that results in a continuous pain and hypersensitivity to stimuli. Neuropathic pain is often a life-long problem for chronic pain sufferers

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

Scientists have known about the HCN2 gene, which is present in pain-sensitive nerve endings, for many years. But its role in regulating pain was not fully understood.
In the study, scientists first isolated the gene from pain-sensitive nerves. Then they used electrical stimuli on the nerves in cell cultures to determine how their properties might change after removing the HCN2 gene.

With promising results from the cell culture studies, the researchers moved their research into another phase by focusing on genetically modified mice that had their HCN2 gene deleted. The scientists subjected the mice to different types of painful stimuli, measuring the speed that the mice moved away from the pain.

Researchers discovered that by deleting the HCN2 gene, they were able to remove neuropathic pain without affecting the mice’s normal response to acute pain, the type of pain experienced by a sudden injury, such as biting your tongue.

“Many genes play a critical role in pain sensation, but in most cases interfering with them simply abolishes all pain, or even all sensation,” said McNaughton. “What is exciting about the work on the HCN2 gene is that removing it or blocking it pharmacologically eliminates neuropathic pain without affecting normal acute pain.”

“If drugs were developed to block the receptors responsible for neuropathic pain I think that it would be an incredible breakthrough in the pain community,” said Dr. Natalie Strand, a University of Southern California professor of Clinical Anesthesiology. Strand, an expert in diabetes and chronic pain treatments, is not aware of any drug companies that have been developing an HCN2 blocker.

“Neuropathic pain is hard to treat,” Strand told American News Report. “It usually doesn’t respond well to narcotics, which is one of our main ways of treating other types of pain. We do have good drugs that have helped with neuropathic pain but they come with their own set of side effects.”

Professor John Wood, who researchers pain at University College London, thinks developing HCN2-blocking therapy will be difficult – and potentially risky for drug companies. Wood told New Scientist magazine that work on HCN2 blockers was abandoned because of the fear of adverse side effects. In addition to regulating pain, HCN2 is also thought to play a role in regulating heartbeat.

Authored by: Neslie Tumulac