Disable neurons to reduce pain: study

Raj Eiamworakul

For the first time, researchers have succeeded in identifying and inactivating neurons in mice responsible for the discomfort and distress that accompany pain, without blocking the nerve signal that indicates an injury.

Until now, the state of knowledge about the phenomenon of pain has prevented the design of targeted pain killers. Some painkillers, such as ibuprofen, offer only limited, local control of pain, while more powerful drugs, such as opioids, reach multiple areas of the brain and easily lead to addiction.

Researchers at Stanford University, California, wanted to trace the origin of the unpleasant sensation of pain in order to develop more precise and effective methods of reducing it.

In studies on the mouse (Nouvelle fenêtre) , these researchers first identified a group of about 100 neurons in the brain that, when inactivated, removed the unpleasant sensation in animals without however, to prevent him from knowing that there was a risk. This discovery could improve treatments for chronic pain.

Pain: feeling in two stages

Pain is a complex sensation that can be broken down into two elements: the signal coming from the damaged area and the unpleasant sensation.

Throughout our body are specialized nerves, called nociceptors, that warn us of an injury and become more sensitive in damaged areas.

During an injury, they emit signals that go back to the brain, where they will be interpreted while crossing several regions, including those that manage emotions and memories. It is at this point that the pain will be associated with an unpleasant sensation, which makes us abruptly move away from the source of the problem and will be remembered in the future.

This reaction is extremely important for survival, and those who do not feel it are more likely to have serious injuries and infections. On the other hand, some types of injury or illness can cause chronic pain that never fades.

Specialized in sensitivity

To find the regions responsible for the uncomfortable aspect of the pain, the Stanford team first became interested in the amygdala, a small area of ​​the brain that plays a role in fear and memory and is important for the interpretation of pain.

First imaging sessions have identified in the mouse a group of a hundred particularly active neurons when it came into contact with a drop of water very hot (but not dangerous).

To understand the role of these neurons, however, it was necessary to study them in a context where the mouse could move freely. To do this, the researchers developed a microscope the size of a paper clip that could be fixed on the head of the mouse and measure its brain activity without interrupting the day.

By repeating the exposure to the drop of water, they noticed that the mouse quickly spread its paws from the source of pain while the same neurons were activated in his brain.

Feel the pain without hurting
It now remained to see what would happen if these neurons no longer worked. Using recent advances in genetic engineering, the researchers managed to disable only the neurons identified in previous experiments.

They then placed the rodents in a special cage divided into three: a section whose floor was very cold, another very hot and a moderate temperature.

The normal mice jumped in contact with the extreme regions and then remained in the temperate zone. Mice with modified neurons also had a defensive recoil reflex when their paws came into contact with extreme temperatures, but they quickly moved around the cage. This reaction shows that they still felt the pain, but that the sensation was no longer unpleasant to them.

Similar results were observed in mice that had developed chronic pain. By deactivating the neurons identified in previous experiments, the researchers noticed that the mice still felt contact in a hypersensitive area, but that their behavior no longer showed that the experience was unpleasant.

For researchers, the discovery of these neurons is a first step to treat chronic pain effectively. In addition, the amygdala is a region whose role is well preserved in both mice and humans, which gives them hope to identify the same neurons in humans. It will however take several years of work before this discovery leads to the development of new drugs.

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