Friday, January 16, 2015

Chronic Pain Associated with Activation of Brain's Glial Cells - Scientific American

Patients with chronic pain show signs of glial activation in brain centers that modulate pain, according to results from a PET-MRI study.

"Glia appears to be involved in the pathophysiology of chronic pain, and therefore we should consider developing therapeutic approaches targeting glia," Dr. Marco L. Loggia from Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, told Reuters Health by email.

"Glial activation is accompanied by many cellular responses, which include the production and release of substances (such as so-called 'pro-inflammatory cytokines') that can sensitize the pain pathways in the central nervous system," he explained. "Thus, glial activation is not a mere reaction to a pain state but actively contributes to the establishment and/or maintenance of persistent pain."

To test their hypothesis that patients with chronic pain demonstrate in vivo activation of brain glia, Dr. Loggia's team imaged the brains of 19 individuals diagnosed with chronic low back pain as well as 25 pain-free healthy volunteers using 11C-PBR28, a PET radioligand that binds to the translocator protein (TSPO), a protein upregulated in activated microglia and reactive astrocytes in animal models of pain.

In the thalamic region of interest, 11C-PBR28 uptake was significantly higher in patients with chronic low back pain than in healthy controls (p<0.01 left thalamus, p<0.05 right thalamus), according to the January 12 Brain online report.

Each patient exhibited higher 11C-PBR28 uptakes than his/her age-, sex-, and TSPO genotype-matched control in the thalamus, and there were no brain regions for which the healthy controls showed statistically higher uptakes than the patients with chronic low back pain.

11C-PBR28 uptakes, and presumably TSPO levels, were negatively associated with pain measures and with circulating levels of proinflammatory cytokines in the chronic pain patients.

"It's important to stress that although TSPO upregulation is a marker of glial activation and therefore of a pro-inflammatory state, animal studies suggest that its role is actually to limit the magnitude of glial responses after their initiation, thereby promoting the return to pre-injury pain-free status and recovery from pain," Dr. 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. Thus, subjects with low levels of pain-related TSPO upregulation on activated glia may be less able to adequately inhibit neuroinflammatory responses, and have a more exaggerated response that ultimately leads to more inflammation and pain."

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http://www.scientificamerican.com/article/chronic-pain-associated-with-activation-of-brain-s-glial-cells/