Papers of the Week

Intrathecal (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 Ca 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 IB+ (nonpeptidergic) and IB- (peptidergic). Intracellular [Ca] microfluorometry and voltage-clamp experiments showed that quinpirole reduced Ca influx and inhibited the high voltage-activated Ca current (HVA-I) in half of IB+ neurons, leaving Ca entry and HVA-I in IB- neurons nearly unaffected. Pretreatment with ω-conotoxin MVIIA prevented the effect of quinpirole on HVA-I from IB+ neurons, indicating that quinpirole mainly inhibits Ca2.2 channels. Immunofluorescence experiments showed that D2 DA receptor was present mainly in IB+ small DRG neurons. Finally, in behavioral experiments in rats, the clinically approved D2-like receptor agonist pramipexole produced spinal antinociception in a similar fashion to quinpirole, with a significant effect only in the mechanonociceptive test. Our results explain, at least in part, why D2-like receptor agonists produce antinociception on mechanonociceptors.