A role for leucine-rich, glioma inactivated 1 in regulating pain sensitivity

This study investigates the role of LGI1, a protein that regulates neuronal excitability, in pain sensitivity. The researchers used transgenic mouse models to genetically ablate LGI1 in specific neuron populations and then assessed the consequences on pain-related sensitivity. The study found that LGI1 is highly expressed in dorsal root ganglion (DRG) and spinal cord dorsal horn neurons in both mice and humans. Ablation of LGI1 resulted in mild thermal and mechanical pain-related hypersensitivity in mice. Further experiments revealed that LGI1 ablation led to hyperexcitability of DRG neurons and spinal dorsal horn neurons, exacerbating mechanical hypersensitivity and allodynia in a spared nerve injury model. The findings suggest an important impact of spinal LGI1 on pathological pain.

• 1
  LGI1 is highly expressed in dorsal root ganglion (DRG) and spinal cord dorsal horn neurons in both mouse and human.
• 2
  Genetic ablation of LGI1 in mice resulted in mild thermal and mechanical pain-related hypersensitivity.
• 3
  LGI1 ablation led to hyperexcitability of DRG neurons, including a reduction in Kv1 currents.
• 4
  LGI1 ablation led to hyperexcitability in spinal dorsal horn neurons, including enhanced wind-up.
• 5
  LGI1 expression was dysregulated in the spinal cord following spared nerve injury.
• 6
  LGI1 ablation exacerbated nerve injury-induced mechanical hypersensitivity and allodynia.