Spinal apolipoprotein E is involved in inflammatory pain via regulating lipid metabolism and glial activation in the spinal dorsal horn

This study investigates how a protein called apolipoprotein E (ApoE) in the spinal cord affects inflammatory pain. Specifically, it looks at how ApoE influences lipid metabolism and the activation of glial cells (astrocytes and microglia) in the spinal dorsal horn, a region important for pain processing. The research uses a mouse model of inflammatory pain induced by complete Freund’s adjuvant (CFA). The researchers examine pain behaviors, gene expression, and cellular changes in normal mice compared to mice lacking ApoE (Apoe−/−) to understand ApoE's role. The findings suggest that ApoE deficiency alters lipid metabolism in astrocytes, which then affects immune responses, astrocyte activation, and neuronal activity. This disruption ultimately reduces the maintenance of inflammatory pain. Targeting APOE could be a potential strategy for pain relief and anti-inflammatory treatments.

• 1
  Apoe levels were markedly upregulated at 2 h and on days 1 and 3 post-CFA treatment, and Apoe was exclusively expressed in the astrocytes.
• 2
  Apoe−/− mice exhibited decreased pain on day 1, but not at 2 h, post-CFA treatment, along with decreased spinal neuron excitability and paw edema.
• 3
  Global transcriptomic analysis revealed that the differentially expressed mRNAs in Apoe−/− mice were associated with lipid metabolism and the immune system, and astrocyte activation was impaired in Apoe−/− mice.