S-ketamine relieves neuropathic pain by inhibiting microglia phagocytosis of the perineuronal nets

Sep 29, 2025Scientific reports

S-ketamine reduces nerve pain by stopping immune cells from breaking down protective nerve structures

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Abstract

C57BL/6 mice with neuropathic pain showed increased microglial activity linked to the degradation of the perineurial network (PNN).

  • Neuropathic pain in mice may be connected to heightened activity that degrades PNN.
  • Minocycline treatment could reduce microglial activity and improve pain thresholds.
  • S-ketamine treatment may enhance pain relief by inhibiting microglial degradation of PNN.
  • The interaction between microglia and PNN may play a key role in the development of neuropathic pain.
  • Microglia-PNN overlap was assessed through 3D reconstruction to measure their spatial relationship.

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Key numbers

10 mg/kg
Pain Threshold Improvement
S-ketamine dosage that effectively reduced pain behavior.
50 mg/kg
Microglial Activation Reduction
Dosage of minocycline that effectively reduced microglial activity.

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