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Targeting Fgr-STAT3 Mediated Autophagy Inhibition in the Spinal Cord Alleviates Neuropathic Pain in Rats.
Liqiong He1,2, Yu Zhang3, Chunguang Yang1,2
1Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, 410000, China.
Neuroscience Bulletin
|April 9, 2026
Summary
Researchers identified Fgr kinase as a key regulator of autophagy in spinal microglia, crucial for neuropathic pain development. Inhibiting Fgr kinase alleviates pain hypersensitivity by restoring microglial autophagy.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Neuropathic pain treatment remains challenging due to poorly understood mechanisms.
- Microglia play a critical role in neuroinflammation and pain signaling.
- Autophagy dysregulation is implicated in various neurological disorders.
Purpose of the Study:
- To investigate the role of Fgr kinase in microglial autophagy during neuropathic pain.
- To identify novel therapeutic targets for neuropathic pain management.
Main Methods:
- Utilized a rat model of chronic constriction injury (CCI) to induce neuropathic pain.
- Employed genetic interventions (Fgr overexpression and knockdown) and behavioral analyses.
- Investigated the molecular mechanisms involving Fgr, STAT3, and autophagic flux markers (LC3-II/LC3-I, SQSTM1).
- Administered pharmacological inhibitor TL02-59 intrathecally.
Main Results:
- CCI induced sustained Fgr expression in spinal dorsal horn (SDH) microglia.
- Fgr overexpression exacerbated, while Fgr knockdown alleviated, neuropathic pain behaviors.
- Fgr directly phosphorylated STAT3, inhibiting autophagic flux and reducing autophagosomes.
- TL02-59 treatment restored autophagy, reduced STAT3 activation, and reversed pain hypersensitivity.
Conclusions:
- The Fgr-STAT3 signaling pathway is a critical regulator of microglial autophagy in neuropathic pain.
- Targeting Fgr kinase offers a promising therapeutic strategy for alleviating neuropathic pain.
