Transcript expression of vesicular glutamate transporters in rat dorsal root ganglion and spinal cord neurons: Impact of spinal blockade during hindpaw inflammation

C. LEIGUARDA; K.H. LUNDGREN; R.P. SEAL; C.J. MCCARTHY; M.F. CORONEL; K.B. SEROOGY; M. CASADEI; H.TRIGOSSO-VENARIO; P.R. BRUMOVSKY

ACS Chemical Neuroscience

ACS Publications

Año: 2020 p. 2602 - 2614

1948-7193

Studies in mouse, and to a lesser extent in rat, have revealed theneuroanatomical distribution of vesicular glutamate transporters (VGLUTs) and begun exposing the critical role of VGLUT2 and VGLUT3 in pain transmission. In the presentstudy in rat we used specific riboprobes to characterize the transcript expression of all threeVGLUTs in lumbar dorsal root ganglia (DRGs) and in the thoracolumbar, lumbar and sacralspinal cord. We show for the first time in rat a very discrete VGLUT3 expression in DRGsand in deep layers of the dorsal horn. We confirm the abundant expression of VGLUT2, bothin DRGs and the spinal cord, including presumable motorneurons in the latter. As expected,VGLUT1 was present in many DRG neuron profiles, and in the spinal cord was mostlylocalized to neurons in the dorsal nucleus of Clarke. In rats with a 10-day long hindpawinflammation, increased spinal expression of VGLUT2 transcript was detected by qRT-PCR,and intrathecal administration of the non-selective VGLUT inhibitor Chicago Sky Blue 6Bresulted in reduced mechanical and thermal allodynia for up to 24 hours. In conclusion, ourresults provide a collective characterization of VGLUTs in rat DRGs and the spinal cord,demonstrate increased spinal expression of VGLUT2 during chronic peripheralinflammation, and support the use of spinal VGLUT blockade as a strategy for attenuatinginflammatory pain.