Pain is a source of substantial discomfort. Abnormal activity in both the zona incerta (ZI) and posterior complex of the thalamus (Po) are implicated in neuropathic pain, but their exact roles remain unclear. In particular, the precise cell types and molecular mechanisms of the ZI-Po circuit that regulate nociception are largely uncharacterized. Here, we found that parvalbumin (PV)-positive neuronal projections from the ventral ZI (ZIv) to the Po (ZIv-Po) are critical for promoting nocifensive behaviors, whereas selectively inhibiting ZIv-Po activity reduces nocifensive withdrawal responses. Furthermore, cannabinoid type 1 receptors (CB₁Rs) are expressed specifically at ZIv-Po axon terminals in this circuit, and cannabinoids attenuate nocifensive responses through presynaptic inhibition. Selective inhibition of the ZIv-Po circuit or administration of cannabinoids into the Po are sufficient to ameliorate pathological pain. These findings identify the critical role of the ZIv-Po circuit and its modulation by endocannabinoids in controlling nocifensive behaviors.

疼痛是造成严重不适的根源。神经病变性疼痛牵涉到不透明带（ZI）和丘脑后复合体（Po）的异常活动，但其确切作用尚不清楚。特别地，调节伤害感受的ZI-Po电路的精确细胞类型和分子机制在很大程度上未表征。在这里，我们发现从腹侧ZI（ZIv）到Po（ZIv-Po）的小白蛋白（PV）阳性神经元投射对于促进伤害行为至关重要，而选择性抑制ZIv-Po活性会降低伤害性戒断反应。此外，大麻素1型受体（CB ₁Rs）专门在此回路中的ZIv-Po轴突末端表达，并且大麻素通过突触前抑制作用减弱伤害反应。选择性抑制ZIv-Po回路或向Po中注入大麻素足以缓解病理性疼痛。这些发现确定了ZIv-Po电路的关键作用及其在控制伤害行为中的内源性大麻素调节作用。