Overview
- After injury, presynaptic neurons release vertebrate lonesome kinase into the synaptic cleft, initiating pain signaling outside cells.
- VLK phosphorylates the extracellular domain of EphB2, which drives NMDA receptors to cluster at synapses and boost signaling.
- Mice lacking VLK in pain-sensing neurons failed to develop postoperative hypersensitivity while maintaining normal movement and sensation.
- Administering VLK to normal mice produced robust, NMDA‑dependent pain responses, and human sensory tissue showed the same EphB2–NMDA interaction.
- Authors propose that extracellular VLK could be blocked locally to modulate NMDA‑related pain pending further research, and the multi‑institution study was published in Science.