Nociceptive stimuli attributes are codified in the periphery; at this level, D2-like dopamine (DA) receptor activation decreases the high voltage-gated Ca²⁺ current predominantly in mechanonociceptive neurons, which explains the presynaptic action mechanism of the antinociception produced by quinpirole when it is intrathecally administered in rats. However, the identity of D2-like DA receptor subtype that mediates this effect remains unknown. To answer this question, we used Fluo-4-based Ca²⁺ microfluorometry to study the depolarization-elicited [Ca²⁺]_i increase in small non-peptidergic DRG neurons (identified by its binding to the Isolectin B₄), and to test the effect of D2-like DA receptor activation by quinpirole in presence of selective antagonists for D2, D3, and D4 DA receptors. The results showed a significantly greater contribution of the D4 DA receptor in the down-modulation of depolarization-elicited [Ca²⁺]_i increase in small non-peptidergic DRG neurons compared to the other receptors. Although the D2 and D3 receptor antagonists also slightly inhibited the effect of quinpirole, their effects were significantly weaker than those of the D4 receptor antagonist. Furthermore, we showed that quinpirole selectively inhibits the Ca_V2.2 Ca²⁺ channels. Our results suggest that the activation of the D4 DA receptors is a promising strategy for pain management at the spinal cord level.

伤害性刺激属性在周围编码；在这个水平上，D2样多巴胺（DA）受体激活主要降低了机械感受感受神经元中的高电压门控Ca ²⁺电流，这解释了喹吡罗在大鼠鞘内给药时产生的镇痛感受的突触前作用机制。然而，介导这种作用的D2样DA受体亚型的身份仍然未知。为了回答这个问题，我们使用了基于Fluo-4-的Ca ²⁺微荧光法研究了去极化引起的小非肽能DRG神经元中[Ca ²⁺ ] _i的增加（通过与Isolectin B _4的结合来确定）），并在存在D2，D3和D4 DA受体选择性拮抗剂的情况下，测试喹吡罗对D2样DA受体激活的影响。结果表明，与其他受体相比，D4 DA受体在小的非肽能DRG神经元中对去极化引起的[Ca ²⁺ ] _i的下调具有显着更大的贡献。尽管D2和D3受体拮抗剂也略微抑制了喹吡罗的作用，但它们的作用明显弱于D4受体拮抗剂。此外，我们显示喹吡罗选择性抑制Ca _V 2.2 Ca ²⁺渠道。我们的结果表明，D4 DA受体的激活是在脊髓水平上进行疼痛控制的有希望的策略。