activation of microglial cells

The study's authors conclude that microglia activated by injury degrade PNNs, which is then
associated with pain sensitivity. Coauthor Arkady Khoutorsky, a neuroscientist at McGill, tells
The Scientist that “we identified a new mechanism of chronic pain.” Specifically, he explains that
the study identifies a mechanism that leads to neuropathic pain—a type of chronic pain caused
by progressive nerve diseases. “We found that the activity of projection neurons can be directly
enhanced in neuropathic pain,” Khoutorsky adds.

Previous studies have shown that the activation of microglial cells after nerve injuries
contributed to the development of neuropathic pain, but the mechanism for this was unclear.
Richard Miller of Northwestern University, who has studied the mechanisms of pain in
osteoarthritis but was not part of the new study, says that its findings are “creative and
unexpected” and that it challenges a previous perception of perineuronal nets as mere structural
supports.

Miller believes that PNNs and other types of extracellular matrix are involved in many pain-
related disorders, including those occurring outside the central nervous system. "There is some
medical evidence that pain can occur when something goes wrong with the extracellular matrix,"
says Miller.