Spinal astrocytic FGFR3 activation leads to mechanical hypersensitivity by increased TNF-α in spared nerve injury

Accumulated studies indicated a crucial role of astrocytes in neuropathic pain (NPP) development, spread and potentiation by a communication with the nervous system. Increased GFAP expression in dorsal horn of the spinal cord indicated the participation of astrocyte in NPP. However, the underlying mechanism is still in need of further investigations.

In our study, the spared nerve injury (SNI) model was established with partial sciatic nerve ligation. The expression status of FGFR3 was studied in spinal dorsal horn of SNI models. The molecular mechanism of spinal astrocytic FGFR3 activation in mechanical hypersensitivity was investigated.

SNI rats showed with hind paw mechanical hypersensitivity and increased GFAP expression in their spinal cords. Increased FGFR3 expression was observed in spinal dorsal horn of SNI models, which was consistent with increased GFAP expression. Elevated FGFR3 upregulates GFAP and TNF-α expression in astrocytes in vivo and in vitro. FGFR3 inhibition by PD173074 lead to downregulation of GFAP and TNF-α and increased withdrawal threshold of SNI models. Mechanically, FGFR3-TBX3 axis activation enhanced TNF-α expression in cultured primary spinal astrocytes. Spinal TNF-α synthesis induced mechanical hypersensitivity in SNI rat models.

FGFR3 is involved in NPP maintenance via FGFR3-TBX3 axis activation induced TNF-α synthesis. FGFR3 and correlated signaling pathways of astrocytes are potential molecular targets for NPP administration.