Scientists Find Brain Cell Key to Easing Long-Term Pain

Scientists in China have found that special immune cells in the spinal cord go through big changes after a nerve injury. These cells, called microglia, act like a cleanup crew for the brain and spine. A gene called Axl was found to control a key part of this cleanup work. Blocking the Axl gene with a drug helped reduce pain in mice with nerve injuries.

Neuropathic pain is pain caused by damaged nerves. It can last for months or years and is very hard to treat. Researchers at Nanjing Medical University wanted to understand why this pain sticks around so long. They hoped that learning more about microglia could lead to better treatments.

The team used a method called the spared nerve injury model in mice. They cut two branches of a nerve in the mouse's leg and left one branch untouched. This caused pain similar to nerve damage in humans. The scientists then studied the spinal cord at 3 days, 7 days, and 14 days after the injury.

Microglia are immune cells that live in the brain and spinal cord. They clean up dead and damaged cells through a process called phagocytosis. The scientists discovered that microglia change how they do this cleanup depending on how long it has been since the injury. These shifts in behavior are closely linked to how pain develops over time.

The researchers used computer tools to study gene activity data from five large published datasets. By looking at which genes were active at each stage, they could track how microglia were changing. One gene kept showing up as especially important: Axl. This gene helps microglia clear away dead cells in a careful process called efferocytosis.

To test Axl's role, the scientists used a drug called R428 to block it. They injected this drug into the spinal fluid of injured mice. After the injection, the mice were less sensitive to touch and cold, which are signs of reduced pain. This showed that Axl plays a real role in how pain develops after nerve injury.

The team also ran lab tests using mouse immune cells called BV2 cells. They used these cells to mimic what happens in the spinal cord after a nerve injury. When they blocked Axl with R428, the cells did not clean up dead neurons as well. This confirmed that Axl is a key part of the cleanup process that affects pain.