A spinoparabrachial circuit defined by Tacr1 expression drives pain

Abstract

Painful stimuli evoke a mixture of sensations, negative emotions and behaviors. These myriad effects are thought to be produced by parallel ascending circuits working in combination. Here, we describe a pathway from spinal cord to brain for ongoing pain. Activation of a subset of spinal neurons expressing Tacr1 evokes a full repertoire of somatotopically directed pain-related behaviors in the absence of noxious input. Tacr1 projection neurons (expressing NKR1) target a tiny cluster of neurons in the superior lateral parabrachial nucleus (PBN-SL). We show that these neurons, which also express Tacr1 (PBN-SL ^Tacr1), are responsive to sustained but not acute noxious stimuli. Activation of PBN-SL ^Tacr1 neurons alone did not trigger pain responses but instead served to dramatically heighten nocifensive behaviors and suppress itch. Remarkably, mice with silenced PBN-SL ^Tacr1 neurons ignored long-lasting noxious stimuli. Together, these data reveal new details about this spinoparabrachial pathway and its key role in the sensation of ongoing pain.