Therapeutic potential of Pak1 inhibition for pain associated with cutaneous burn injury

Burn injuries often lead to chronic pain, which is difficult to treat. This study explores a new approach by targeting a protein called Pak1, which is involved in how nerve cells change after injury. Inhibiting Pak1 with an existing drug, romidepsin, showed promise in reducing pain and nerve cell changes in mice with burn injuries. The researchers used a mouse model of second-degree burn injury to test if inhibiting Pak1 could reduce pain. They observed that after a burn, mice experienced increased sensitivity to touch and heat, along with changes in the structure of nerve cells in the spinal cord. Treatment with romidepsin, a drug already approved for other conditions, reduced these nerve cell changes and improved the mice's pain thresholds. However, when the treatment stopped, the pain and nerve cell abnormalities returned, suggesting that Pak1 inhibition could be a potential therapeutic target for burn-induced pain.

• 1
  Inhibition of Pak1 by romidepsin decreased dendritic spine dysgenesis in the dorsal horn of mice with burn injury.
• 2
  Romidepsin treatment reduced c-fos expression, an indicator of elevated central nociceptive activity, in dorsal horn neurons.
• 3
  Romidepsin treatment rescued pain thresholds in mice with burn injury, but drug discontinuation resulted in a relapse of cellular correlates of pain and lower pain thresholds.