Perineuronal nets play unexpected role in chronic pain

By | July 31, 2022

R. Douglas Fields writes:

Neuroscientists, being interested in how brains work, naturally focus on neurons, the cells that can convey elements of sense and thought to each other via electrical impulses. But equally worthy of study is a substance that’s between them — a viscous coating on the outside of these neurons. Roughly equivalent to the cartilage in our noses and joints, the stuff clings like a fishing net to some of our neurons, inspiring the name perineuronal nets (PNNs). They’re composed of long chains of sugar molecules attached to a protein scaffolding, and they hold neurons in place, preventing them from sprouting and making new connections.

Given this ability, this little-known neural coating provides answers to some of the most puzzling questions about the brain: Why do young brains absorb new information so easily? Why are the fearful memories that accompany post-traumatic stress disorder (PTSD) so difficult to forget? Why is it so hard to stop drinking after becoming dependent on alcohol? And according to new research from the neuroscientist Arkady Khoutorsky and his colleagues at McGill University, we now know that PNNs also explain why pain can develop and persist so long after a nerve injury.

Neural plasticity is the ability of neural networks to change in response to experiences in life or to repair themselves after brain injury. Such opportunities for effortless change are known as critical periods when they occur early in life. Consider how easily babies pick up language, but how difficult it is to learn a foreign language as an adult. In a way, this is what we’d want: After the intricate neural networks that allow us to understand our native language are formed, it’s important for them to be locked down, so the networks remain relatively undisturbed for the rest of our lives.

This means that after a critical period, neural networks become resistant to change, and PNNs are a major reason why. They form over neurons and lock neural network wiring in place at the end of the critical period. This happens most often between the ages of 2 and 8, but PNNs also form on neurons in adulthood in association with behaviors that are hard to break, or in the formation of long-term memories. If we could delay the closure of critical periods, or somehow reopen them later in life, this would restore youthful neural plasticity, promote recovery from injury and undo difficult neurological disorders that are resistant to change. [Continue reading…]

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