While numerous studies have clearly associated glial activation with persistent pain in animal models, none have 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 – 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’s integrated PET/MR scanners using a new radiopharmaceutical that binds to the translocator protein (TSPO). Loggia and colleagues found that the levels of the protein 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 notes, that it was possible to spot which were the patients and which were the controls just by looking at the individual images prior to detailed statistical analysis of the data.
Another interesting finding was that among patient participants, who had been asked to report their current levels of pain during the imaging session, those with the highest levels of TSPO had reported lower levels of pain. Loggia explains, “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. 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.”
An assistant professor of Radiology at Harvard Medical School, Loggia notes 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.