Modulation of Thalamic Nociceptive Processing after Spinal Cord Injury through Remote Activation of Thalamic Microglia by Cysteine–Cysteine Chemokine Ligand 21

Spinal cord injury (SCI) can lead to chronic pain, partly due to changes in nerve cell excitability. This study investigates the role of microglia, immune cells in the brain, in the thalamus, a brain region involved in pain processing, after SCI. The researchers found that a molecule called CCL21, which activates microglia, is increased in the spinal cord and thalamus after SCI. Blocking CCL21 in the thalamus reduced microglial activation and pain. This suggests that SCI triggers the release of CCL21, which then activates microglia in the thalamus, contributing to the development of chronic pain. Targeting this pathway could potentially offer new ways to treat pain after SCI.

• 1
  CCL21 is upregulated in dorsal horn neurons and tissue levels are increased in the dorsal horn and VPL nucleus of the thalamus 4 weeks after SCI.
• 2
  Intra-VPL antibody-mediated neutralization of CCL21 decreases microglial activation and evoked hyperexcitability of VPL neurons, restoring nociceptive thresholds to near-normal levels.
• 3
  Electrical stimulation of the spinothalamic tract in intact animals increases thalamic CCL21 levels, and recombinant CCL21 injected into the VPL induces microglial activation and pain-related behaviors.