CHRONIC PAIN wrecks the lives of more than 600m people around the world. One in five adults struggles with it. What causes it, however, is often a mystery. The prevailing hypothesis is that, after an injury, something goes wrong with the body’s pain receptors and the alarm system that reports injuries to the brain keeps ringing long after the body has finished healing. Even when there is a clear underlying cause, such as arthritis or nerve damage, it is not known exactly how those conditions produce pain. Treatments, therefore, often bring little relief.
Scientists have identified a protein involved in transporting molecules related to pain across nerve cells, which they believe could be responsible for long-lasting pain. (PIXABAY)
In a paper published in Nature on August 20th, scientists report a discovery that could turn things around. They have identified a protein involved in transporting molecules related to pain across nerve cells, which they believe could be responsible for long-lasting pain. Drugs targeting this protein, or even cutting certain foods that interact with its function, could make for potent new treatments.
The scientists, who were led by David Bennett from the University of Oxford, began by scouring genomic data in the UK Biobank, a repository of health records and biological samples from more than 500,000 people. They knew from previous studies on twins that genetics seems to play a role in about a third of chronic-pain cases. So they thought that there might be a variant of a gene that would show up more frequently among sufferers of chronic pain than in the general population.
Several genetic signals emerged from the biobank. One came from a variant of a gene called SLC45A4. This gene caught the researchers’ attention because its DNA sequence suggested that it regulates the activity of a “transporter” molecule—proteins that move ions, small molecules and drugs between cells and between the various compartments within a cell. For scientists looking for a biological pathway, finding a transporter molecule is often the first, crucial clue.
Even more promising, the transporter regulated by the gene turned out to be involved in moving around polyamines, a group of molecules suspected of controlling pain. (This suspicion is based on the fact that people with arthritis have higher levels of polyamines in their blood and tissues.) To test their hunch that this gene could interfere with polyamine transport and consequently pain, the researchers bred some mice in which they turned off the SLC45A4 gene entirely. It confirmed that they had hit upon a new pain-regulating pathway: the creatures were less sensitive to pain than those with intact genes.
A lot more research needs to be done, says Dr Bennett. The gene variant highlighted by the study is common; it is found in 45% of people in Britain. For that reason, it is unlikely to be the only thing influencing chronic pain and may turn out to be more important in some people than others.
Nonetheless, the new discovery presents a promising new target, and not just for drugs. A number of things can alter a person’s polyamine levels, says Dr Bennett. Some foods have higher levels of polyamines; gut microbes produce them too. Although it is unclear exactly how polyamine levels in the body affect chronic pain, it is possible that cutting out certain foods could one day form the basis of treatment, too. With luck, a more comfortable future awaits.
E-Paper
