A craniofacial-specific monosynaptic circuit enables heightened affective pain

• Published in: Nature neuroscience Vol. 20; no. 12; pp. 1734 - 1743
• Main Authors: Rodriguez, Erica, Sakurai, Katsuyasu, Xu, Jennie, Chen, Yong, Toda, Koji, Zhao, Shengli, Han, Bao-Xia, Ryu, David, Yin, Henry, Liedtke, Wolfgang, Wang, Fan
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.12.2017
• Subjects: Affect; Afferent Pathways - physiopathology; Animals; Avoidance behavior; Behavior, Animal; Circuits; Conditioning, Operant; Facial Pain - physiopathology; Facial Pain - psychology; Female; Genes, fos - genetics; Male; Mice; Mice, Inbred C57BL; Neural circuitry; Neural networks; Neurons; Neurophysiology; Nociceptors; Optogenetics; Pain; Pain perception; Parabrachial nucleus; Physical Stimulation; Sensory neurons; Skull; Synapses
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/s41593-017-0012-1

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 ), 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 neurons and performed comprehensive anatomical input-output mapping. Surprisingly, we uncovered a hitherto uncharacterized monosynaptic connection between cranial sensory neurons and the PB -nociceptive neurons. Optogenetic activation of this monosynaptic craniofacial-to-PB 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.