The influence of PNNs on chronic pain was discovered recently, despite the fact that neuroscientists have known about these aspects for a long time. This work further extends the nets influence beyond critical periods and improves our understanding of the basic science of pain.
It can be difficult to overcome chronic pain, which is a reflection of a change in the brain. Our entire body is involved when something hurts. Neural impulses are sent to the brain from the spine. Doctors often manage the pain of childbirth by injecting anesthetics into the space surrounding the back of the neck, blocking neural impulses from reaching the brain.
Imagine if a nerve injury made the neurons sensitive. A gentle touch in the affected area would cause a cascade of brain impulses to travel up the spine. No one expected PNNs to be involved in the research that found several mechanisms that can cause such hypersensitization.
A few years ago, Khoutorsky saw a paper that reported on the coating of small neurons in a brain region. The interneurons form on the pain neurons and prevent them from sending pain signals. Khoutorsky wondered if PNNs might be doing something similar at the critical pain relay point inside the spine and asked his graduate student to look into it. No one knew at that time.
Tansley found that pain signals from the spine were relayed to the brain. There are long axons that point up the spine to the brain. They have a set of interneurons that attach to them through small holes in the PNN, and the interneurons can block the firing of long projecting neurons, which can make it hard to feel pain. Tansley was surprised to discover that there were only inhibitory neurons in the relay point.
The finding inspired Khoutorsky's team to conduct experiments on laboratory mice to see if the nets were involved in chronic pain. The sciatic nerve is a part of the hind leg of a mouse. sciatic injuries are known to cause persistent pain Khoutorsky's team measured the mouse's pain threshold with non- harmful tests such as timing how quickly it recoiled from a warmed surface. The team noticed that the mouse display had increased insensitivity to pain, but they also noticed that the PNNs had dissolved. The changes in the brain and spine of a mouse are similar to the changes in the brain and spine of a human.
The team was able to figure out what was causing the nets to be destroyed. The team performed the same operation on mice with no microglia as they did on mice with them. The mice did not become hypersensitive to pain after the sciatic nerve surgery. The team used a variety of methods to confirm the connection.
It was proven that the PNNs were suppressing pain sensitivity. Khoutorsky's team was able to find out how it works. The signalling from the projecting neurons that send pain signals to the brain was increased when the PNNs were degraded. Runaway neural firing and intense pain were caused by the loss of their brakes.
There are many substances that cause pain neurons to become hypersensitive after nerve injury, but their unexpected action on PNNs has an advantage. Khoutorsky said that perineuronal nets protect cells. The nets are only around the pain relay neurons. He thinks that the pain relay point in the spine is so important that it needs protection so that its control of pain transmission is reliable. Neural injuries can disrupt that stability.
The mechanism is good for specific cell types. The substances microglia release to increase neural firing and cause pain after neural injury affect all types of cells in the vicinity.
The mechanism of chronic pain is being studied. There is an urgent need for a new treatment for chronic pain due to the fact that opiates, the current solution, lose their potency over time and can become addictive.
Neural networks are formed by individual neurons linking together, but the neglected cartilaginous cement in the space between them is crucial.
All Rights Reserved © 2024
