A group of drugs being developed to treat mood disorders could
also relieve chronic pain, finds new UCL (University College
London) research funded by the Medical Research Council.
The study reveals how a protein that shapes the body's response
to stress also drives chronic pain and so offers new targets for
future pain treatments.
The researchers studied genetically modified mice that lacked a
protein called FKBP51. This protein is very important for
regulating stress. Variations in the human FKBP5 gene are linked to
the risk of developing stress-related psychiatric disorders, such
as major depression and post-traumatic stress disorder (PTSD).
Previous studies have shown that people with specific FKBP5
variations feel greater physical pain after serious trauma, and the
UCL team have now discovered that mice without FKBP51 experience
reduced chronic pain from nerve damage and arthritic joints.
"Inhibiting FKBP51 has a very powerful effect in mice with
chronic pain," says lead author Dr Maria Maiarù of UCL. "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."
The team then tested an FKBP51-blocking compound called SAFit2,
developed by Dr Felix Hausch at the Max Planck Institute of
Psychiatry to treat mood disorders by acting in the brain to reduce
anxiety. By selectively blocking FKBP51 in the spinal cord, the UCL
researchers were able to test its effects on chronic pain
independently of its known effects on the brain. They found that
SAFit2 substantially alleviated chronic pain in mice, making it a
promising candidate for drug development.
"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," says senior author Dr
Sandrine Géranton of UCL. "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."
The study also showed that an injury can trigger long-term
epigenetic changes in spinal cord sensory circuits. This in turn
leads to increased production of FKBP51 which contribute to the
body's pain response.
"FKBP51 in the brain can prolong the stress response after
trauma and we have found that it also exacerbates the pain
response," explains Dr Géranton. "Although this may have once had
an evolutionary advantage in promoting survival, in our current
lifestyles it can lead to chronic pain, depression and PTSD.
Chronic pain affects one in five adults worldwide and there are
currently no effective treatments, so we are extremely excited to
have identified a new treatment target."
The paper, The stress
regulator FKBP51 drives chronic pain by modulating spinal
glucocorticoid signaling, is published in Science
Translational Medicine.