A craniofacial-specific monosynaptic circuit enables heightened affective pain

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 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 the hindpaw. Using a novel activity-dependent technology called CANE developed in our lab, we identified and selectively labeled noxious stimuli-activated PB(L) neurons, and performed comprehensive anatomical input-output mapping. Surprisingly, a hitherto uncharacterized monosynaptic connection between cranial sensory neurons and the PB(L)-nociceptive neurons was uncovered. Optogenetic activation of this monosynaptic craniofacial-to-PB(L) projection induced robust escape/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.