High voltage-activated (HVA) Ca (Ca) channels are oligomeric complexes formed by an ion-conducting main subunit (Cavα) and at least two auxiliary subunits (Cavβ and Caαδ). It has been reported that the expression of Caαδ1 increases in the dorsal root ganglia (DRGs) of animals with mechanical allodynia, and that the transcription factor Sp1 regulates the expression of the auxiliary subunit. Hence, the main aim of this work was to investigate the role of Sp1 as a molecular determinant of the exacerbated expression of Caαδ-1 in the nerve ligation-induced model of mechanical allodynia. Our results show that ligation of L5/L6 spinal nerves (SNL) produced allodynia and increased the expression of Sp1 and Caαδ-1 in the DRGs. Interestingly, intrathecal administration of the Sp1 inhibitor mithramycin A (Mth) prevented allodynia and decreased the expression of Sp1 and Caαδ-1. Likewise, electrophysiological recordings showed that incubation with Mth decreased Ca current density in the DRG neurons, acting mostly on HVA channels. These results suggest that L5/L6 SNL produces mechanical allodynia and increases the expression of the transcription factor Sp1 and the subunit Caαδ-1 in the DRGs, while Mth decreases mechanical allodynia and Ca currents through HVA channels in sensory neurons by reducing the functional expression of the Caαδ-1 subunit.