Transcription Factor Sp1 Regulates the Expression of Calcium Channel α2δ-1 Subunit in Neuropathic Pain

Publication date: Available online 18 June 2019Source: NeuroscienceAuthor(s): Kimberly Gómez, Alejandro Sandoval, Paulino Barragán-Iglesias, Vinicio Granados-Soto, Rodolfo Delgado-Lezama, Ricardo Felix, Ricardo González-RamírezAbstractHigh voltage-activated (HVA) Ca2+ (CaV) channels are oligomeric complexes formed by an ion-conducting main subunit (Cavα1) and at least two auxiliary subunits (Cavβ and CaVα2δ). It has been reported that the expression of CaVα2δ1 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 CaVα2δ-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 CaVα2δ-1 in the DRGs. Interestingly, intrathecal administration of the Sp1 inhibitor mithramycin A (Mth) prevented allodynia and decreased the expression of Sp1 and CaVα2δ-1. Likewise, electrophysiological recordings showed that incubation with Mth decreased Ca2+ 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 ...
Source: Neuroscience - Category: Neuroscience Source Type: research

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