Mechanism of sustained chronic neuropathic pain

It is known that dorsal root ganglion (DRG) satellite glial cells (SGCs) activation leads to neuroinflammation and persistent pain but the underlying mechanisms driving prolonged SGC activation is not well understood.

The authors show that non-receptor tyrosine kinase FGR is increased in DRG SGCs following peripheral nerve injury via NF-κB signaling and inhibition or genetic knockdown of FGR significantly attenuates SGC activation and pain hypersensitivity.

The researchers demonstrate mechanistically that FGR binds p65 at Ser238/240, causing persistent phosphorylation of p65 at Ser536 in SGCs and nuclear-accumulated p65 sustains FGR upregulation and neuroinflammation under neuropathic pain.

https://www.cell.com/cell-reports/fulltext/S2211-1247(25)01671-7

https://sciencemission.com/FGR-and-p65-sustains-satellite-glial-cell-activation