Researchers have found the first evidence of neuro-inflammation in the brains of chronic pain patients, a development that could lead to new treatments and better ways to measure the presence and intensity of pain.
Previous studies in animals have shown that elevated levels of an inflammation-linked protein in the brain are involved in the transmission of pain.
In the new study, published online in the journal Brain, researchers at Massachusetts General Hospital (MGH) enrolled 10 patients with chronic lower back pain and 9 healthy control participants. Brain images of the participants were conducted with a PET/MR scanner using a new radiopharmaceutical that binds to the translocator protein (TSPO).
Researchers found that levels of the protein in the thalamus and other brain regions were significantly higher in patients than in controls subjects. Elevated levels of the protein were so clear in the images that it was possible to spot which were the patients and which were the controls just by looking at them.
In the two images below, PET scan data from a chronic pain patient with lower back pain (left) and a healthy control subject (right) reveal higher levels of inflammation-associated protein (orange/red areas) in the thalamus and other brain regions of the pain patient.
“Finding increased levels of the translocator protein in regions like the thalamus – the brain’s sensory gateway for pain and other stimuli – is important, since we know that this protein is highly expressed in microglia and astrocytes, the immune cells of the central nervous system, when they are activated in response to some pathologic event,” says lead author Marco Loggia, PhD, of the MGH-based Martinos Center for Biomedical Imaging.
“Demonstrating glial activation in chronic pain suggests that these cells may be a therapeutic target, and the consistency with which we found glial activation in chronic pain patients suggests that our results may be an important step towards developing biomarkers for pain conditions.”
Another interesting finding is that when patients were asked to report their current levels of pain during the imaging session, those with the highest levels of TSPO reported lower levels of pain.
“While upregulation of TSPO is a marker of glial activation, which is an inflammatory state, animal studies have suggested that the protein actually limits the magnitude of glial response after its initiation and promotes the return to a pain-free, pre-injury status. This means that what we are imaging may be the process of glial cells trying to ‘calm down’ after being activated by the pain,” said Loggia.
“Those participants with less pain-related upregulation of TSPO may have a more exaggerated neuroinflammatory response that ultimately leads to more inflammation and pain. While larger studies would be needed to further support this interpretation, this evidence suggests that drugs called TSPO agonists, which intensify the action of TSPO, may benefit pain patients by helping to limit glial activation.”
Loggia says future studies should investigate whether the same glial activation patterns are seen in patients with other forms of chronic pain or whether particular “glial signatures” may differentiate between different pain syndromes.