A new group of drugs that are being developed primarily to treat mood disorders may also help patients with chronic pain, according to a new study by researchers from the University College London. The study reveals that a protein integral in shaping the body's stress response is also a driver of chronic pain, offering scientists new potential targets for pain treatments.
The team revealed the findings through the analysis of genetically modified mice that lacked the FKBP51 protein, which is important for stress regulation. In humans, variations of the FKBP5 gene are connected to the development of stress-related mental disorders such as depression and post-traumatic stress disorder (PTSD). Furthermore, people with specific FKBP5 variations are subject to an increased amount of physical pain after serious trauma or injury.
The results of the current study found that mice that lack FKBP51 experience less chronic pain resulting from nerve damage and joint arthritis.
"Inhibiting FKBP51 has a very powerful effect in mice with chronic pain," Maria Maiarù, lead author of the study, said in a press release. "Not only does it block the pain from their injury without affecting their normal pain response, it also makes them more mobile. We did not find any negative side-effects."
After this discovery, the team tested SAFit2, an FKBP51-blocking compound designed to treat mood disorders, by selectively blocking FKBP51 in the spinal cord, allowing them to test its effects on chronic pain separate from its effects on the brain. The results showed that SAFit2 reduced chronic pain in mice, pointing to its potential as a drug development candidate.
"The compound was designed to have positive effects on mental health, but we have discovered that it also has significant benefits for physical pain syndromes," said Sandrine Géranton, senior author of the study. "Who wouldn't want a treatment that relieves chronic pain while also making you less stressed? This was an experimental study with mice, but if this could be successfully translated into a treatment for patients, it would be a win-win."
Furthermore, injury can stimulate lasting epigenetic changes in the spinal cord's sensory circuits, which leads to increased FKBP51 production that likely affects the body's pain response. The team believes that this response may have had an evolutionary advantage in the past but now acts as a debilitating biological process that promotes chronic pain in our current environment and lifestyles.
The findings were published in the Feb. 10 issue of Science and Translational Medicine.
