Chronic pain can ruin a person’s quality of life, and treating chronic pain is extremely challenging because many of the treatments, like opioids, can lead to more problems. Scientists have been searching for alternative treatment options for chronic pain, and new research reported in Nature has revealed more about the molecules that are closely connected to the sensation of pain. It may eventually be possible to block some of these molecules and mechanisms in a new pain treatment approach.
When people experience chronic pain, neurons called nociceptors that sense injury and damage can become overactive, and flood the brain with pain signals. High levels of molecules known as polyamides are thought to cause neurons to be overly sensitive, send too many pain signals to the brain, and lead to chronic pain.
In this study, investigators discovered that many of people who often report higher levels of pain also typically carry a variant of a gene called SLC45A4. This variant was then confirmed in many others who report high pain levels in different genetic databases.
The scientists found that this gene encodes for a neuronal polyamide transporter, which is related to how neurons react to pain signals.
"This has broadened our understanding of pain signaling in the body and opened new avenues of research directed at treating chronic pain. Our work exemplifies the power of discovery science and multidisciplinary collaboration,” said first study author Dr. Steven Middleton of The University of Oxford.
Next, the research team revealed the three-dimensional structure of SLC45A4, and demonstrated that it can send polyamines to neurons.
The dorsal root ganglion (DRG), where neurons take information from the body and send it too the brain, also expresses high levels of SLC45A4. Neurons of the DRG can detect pain.
When a mouse model was engineered to lack SLC45A4, their reaction to a painful stimulus was reduced.
Although more research will be needed, this work could eventually be transformative for the treatment of chronic pain.
"We discovered a new pain gene, gained insights into the atomic structure of this molecule, and connected its function to the excitability of neurons that respond to tissue injury. Ultimately, our findings reveal a promising new target for the treatment of chronic pain,” said co-corresponding study author Professor David Bennett of The University of Oxford.
Sources: University of Oxford, Nature