Cellular Mechanism for Specific Mechanical Antinociception by D2-like Receptor at the Spinal Cord Level

Publication date: Available online 17 August 2019Source: NeuroscienceAuthor(s): Angélica Almanza, Pedro Segura-Chama, Martha León-Olea, Enoch Luis, René Garduño-Gutiérrez, Jonathan Mercado-Reyes, Karina Simón-Arceo, Ulises Coffeen, Arturo Hernández-Cruz, Francisco Pellicer, Francisco MercadoAbstractIntrathecal (i.t.) administration of quinpirole, a dopamine (DA) D2-like receptor agonist, produces antinociception to mechanonociceptive stimuli but not to thermonociceptive stimuli. To determine a cellular mechanism for the specific antinociceptive effect of D2-like receptor activation on mechanonociception, we evaluated the effect of quinpirole on voltage-gated Ca2+ influx in cultured dorsal root ganglion (DRG) neurons and the D2 DA receptor distribution in subpopulations of rat nociceptive DRG neurons.Small-diameter DRG neurons were classified into IB4 + (nonpeptidergic) and IB4- (peptidergic). Intracellular [Ca2+] microfluorometry and voltage-clamp experiments showed that quinpirole reduced Ca2+ influx and inhibited the high voltage-activated Ca2+ current (HVA-ICa) in half of IB4 + neurons, leaving Ca2+ entry and HVA-ICa in IB4- neurons nearly unaffected. Pretreatment with ω-conotoxin MVIIA prevented the effect of quinpirole on HVA-ICa from IB4 + neurons, indicating that quinpirole mainly inhibits CaV2.2 channels. Immunofluorescence experiments showed that D2 DA receptor was present mainly in IB4 + small DRG neurons. Finally, in behavioral experimen...
Source: Neuroscience - Category: Neuroscience Source Type: research