Neuroligin1 Contributes to Neuropathic Pain by Promoting Phosphorylation of Cofilin in Excitatory Neurons

This study investigates the role of Neuroligin1 (NL1) in neuropathic pain, a chronic condition resulting from nerve damage. The researchers focused on how NL1, a protein found in excitatory neurons, contributes to this type of pain. Using genetically modified mice, the study found that NL1 is upregulated in the spinal dorsal horn following spared nerve injury (SNI), a model for neuropathic pain. This upregulation is associated with increased levels of phosphorylated cofilin (p-cofilin) and GluR1. By reducing NL1 expression in excitatory neurons, the researchers were able to alleviate the pain-induced hypersensitivity and reduce the levels of p-cofilin and GluR1. This suggests that NL1 in excitatory neurons plays a critical role in regulating neuropathic pain.

• 1
  NL1 is upregulated in the L4–L6 spinal dorsal horn in Vglut2-cre+/−mouse subjected to spared nerve injury (SNI).
• 2
  The expression of phosphorylated cofilin (p-cofilin) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 1 (GluR1) was also increased.
• 3
  Spinal microinjection of a cre-dependent NL1-targeting RNAi in Vglut2-cre+/−mouse alleviated the neuropathic pain-induced mechanical hypersensitivity and reduced the increase in p-cofilin and GluR1 caused by SNI.