Humans often rank craniofacial pain as more severe than body pain. Evidence suggests that a stimulus of the same intensity induces stronger pain in the face than in the body. However, the underlying neural circuitry for the differential processing of facial versus bodily pain remains unknown. Interestingly, the lateral parabrachial nucleus (PB_L), a critical node in the affective pain circuit, is activated more strongly by noxious stimulation of the face than of the hindpaw. Using a novel activity-dependent technology called CANE developed in our laboratory, we identified and selectively labeled noxious-stimulus-activated PB_L neurons and performed comprehensive anatomical input–output mapping. Surprisingly, we uncovered a hitherto uncharacterized monosynaptic connection between cranial sensory neurons and the PB_L-nociceptive neurons. Optogenetic activation of this monosynaptic craniofacial-to-PB_L projection induced robust escape and avoidance behaviors and stress calls, whereas optogenetic silencing specifically reduced facial nociception. The monosynaptic circuit revealed here provides a neural substrate for heightened craniofacial affective pain.

中文翻译：

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颅面特定的单突触回路使情绪疼痛加重

人类通常将颅面部疼痛列为比身体疼痛更严重的等级。有证据表明，相同强度的刺激会比人体内引起更大的面部疼痛。然而，用于面部和身体疼痛的差异处理的潜在神经回路仍然未知。有趣的是，外侧臂臂旁核（PB _L）是情感性疼痛回路中的关键节点，其对面部的有害刺激比对后爪的激活更为强烈。使用我们实验室开发的一种新的依赖活动的技术，称为CANE，我们鉴定并选择性标记了有害刺激激活的PB _L神经元并执行了全面的解剖学输入-输出映射。出人意料的是，我们发现了颅内感觉神经元和PB _L-伤害感受性神经元之间迄今未表征的单突触连接。这种单突触的颅面至PB _L投射的光遗传学激活诱导了稳健的逃避和回避行为以及应激反应，而光遗传学沉默则特别减少了面部伤害感受。这里揭示的单突触回路为神经颅底情感疼痛的加剧提供了神经基础。