IRG1/itaconate increases IL-10 release to alleviate mechanical and thermal hypersensitivity in mice after nerve injury

This study investigates the role of itaconate, a metabolite produced by immune-responsive gene 1 (IRG1), in neuropathic pain. The researchers found that itaconate levels increase in the spinal cord after nerve injury. They also discovered that mice lacking IRG1 experienced worsened pain hypersensitivity, suggesting that endogenous itaconate has an analgesic effect. The administration of 4-octyl itaconate (4-OI), a derivative of itaconate, alleviated neuropathic pain in mice. Further investigation revealed that 4-OI increases the level of Interleukin-10 (IL-10), an anti-inflammatory cytokine, in the spinal cord, activating the STAT3/β-endorphin pathway, which mediates the pain-relieving effect of itaconate. This study suggests that targeting the spinal IL-10/STAT3/β-endorphin pathway could be a potential strategy for treating neuropathic pain.

• 1
  The levels of itaconate and IRG1 in the spinal cord significantly increased after CCI (chronic constriction nerve injury).
• 2
  Irg1 deficiency aggravated the mechanical and heat hypersensitivity in mice after nerve injury, indicating an endogenous analgesic role.
• 3
  Exogenous administration of the itaconate derivative 4-OI alleviated neuropathic pain in male and female CCI mice by increasing IL-10 levels and activating the STAT3/β-endorphin pathway in the spinal cord.