By SUE McGREEVEY
January 12, 2015
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.
For more on Brain and Mental Performance
Adapted from a Mass General news release.
http://hms.harvard.edu/news/pain-brain
— Last Edited by Greentea at 2015-01-15 07:06:42 —
