Harvard Medical School. US: Imaging study finds first evidence of neuroinflammation in brains of chronic pain patients. Harvard Medical School researchers at Massachusetts General Hospital
have found, for the first time, evidence of neuroinflammation in key
regions of the brains of patients with chronic pain.
By showing that levels of an inflammation-linked protein are elevated
in regions known to be involved in the transmission of pain, the study
published in the journal Brain opens
up exploration of potential new treatment strategies and identifies a
possible way around one of the most frustrating limitations in the study
and treatment of chronic pain: the lack of an objective way to measure
the presence or intensity of pain.
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,”
said Marco Loggia, assistant professor of radiology at Mass General and lead author of the report.
“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,” Loggia said.
While numerous studies have clearly associated glial activation
with persistent pain in animal models, none has previously documented
glial activation in the brain of humans with chronic pain. The current
study initially enrolled 19 patients with chronic lower back pain and 25
healthy control participants. In a subset of 10 patients and 9
pain-free controls who were carefully selected from the initial larger
group based on sex, age and genetic characteristics, brain imaging
studies were conducted with one of the Martinos Center for Biomedical
Imaging’s integrated PET/MR scanners using a new radiopharmaceutical
that binds to the translocator protein.
Loggia and colleagues found that translocator protein levels in the
thalamus and other brain regions were significantly higher in patients
than in controls. The PET signal increases were so remarkably consistent
across participants, Loggia noted, that it was possible to spot who
were the patients and who were the controls just by looking at the
individual images prior to detailed statistical analysis of the data.
Among patient participants who had been asked to report their current
levels of pain during the imaging session, those with the highest
levels of the translocator protein had reported lower levels of pain.
“While upregulation of the translocator protein 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,” Loggia explained. “This means that what we are
imaging may be the process of glial cells trying to ‘calm down’ after
being activated by the pain.”
Those participants with less pain-related upregulation of the
translocator protein may have a more exaggerated neuroinflammatory
response that ultimately leads to more inflammation and pain, Loggia
said. While larger studies would be needed to further support this
interpretation, this evidence suggests that drugs called translocator
protein agonists, which intensify the action of the translocator
protein, may benefit pain patients by helping to limit glial activation.
Loggia noted that the ability to image glial activation could
identify patients for whom the drugs targeting the process would be most
appropriate. 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 specific
syndromes or pathologic mechanisms.
Additional co-authors of the Brain paper include senior author Jacob Hooker, HMS associate professor of radiology at Mass General, and Bruce Rosen, the Laurence Lamson Robbins Professor of Radiology at HMS and Mass General.
Support for the study includes grants from the National Institute of
Neurological Disorders and Stroke, National Center for Advancing
Translational Science and the National Center for Research Resources.