Objective   To explore whether dexamethasone (Dex) has a rapid nongenomic effect on the intracellular calcium concentration ([Ca

2+

]

i) increase after ATP inducement in rat dorsal root ganglion (DRG) neurons.    Methods   DRG neurons were isolated from SD rats at the age of 2 to 3 weeks and then plated on cover slips. The effects of Dex (1 μmol/L) on ATP-induced [Ca

2+

]

i increase were studied on cultured DRG neurons using single-cell Ca

2+

microfluorometry

respectively combined

with G-protein activation inhibitor GDP-β-S (0.5 mmol/L)

glucocorticoid receptor antagonist RU38486 (10 μmol/L)

protein kinase A inhibitor H89 (10 μmol/L)

or protein kinase C inhibitor chelerythrine chloride (Che

10 μmol/L).    Results   ATP (100 μmol/L) caused the increase of [Ca

2+

]

i transients in DRG neurons via activation of P2X receptor. A 5 min incubation with Dex inhibited ATP-induced [Ca

2+

]

i increase in DRG neurons in a concentration-dependent manner. Dex inhibitory effect on ATP-induced [Ca

2+

]

i transients were blocked by RU38486 and H89

but not GDP-β-S and Che.    Conclusion   Dex can inhibit ATP-induced [Ca

2+

]

i increase in DRG neurons. The inhibitory effect of Dex may be mediated by glucocorticoid receptor through activating protein kinase A signal pathway. Our results demonstrate an nongenomic effect of Dex on the excitability of dorsal root ganglion neurons by regulating ATP-induced [Ca

2+

]

i transients

which may be relevant for relieving pain in the stressful event.