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 showed that these neurons, which also express Tacr1 (PBN-SLTacr1), are responsive to sustained but not acute noxious stimuli. Activation of PBN-SLTacr1 neurons alone did not trigger pain responses but instead served to dramatically heighten nocifensive behaviors and suppress itch. Remarkably, mice with silenced PBN-SLTacr1 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.
- Alexander Theodore Chesler
- Ariel J Levine
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Animal experimentation: All surgical, experimental and maintenance procedures were carried out in accordance in accordance with a protocol approved by the National Institute for Neurological Diseases and Stroke (NINDS) Animal Care and Use Committee (ASP1365 and ASP1369).
- Allan Basbaum, University of California San Francisco, United States
- Received: July 16, 2020
- Accepted: February 15, 2021
- Accepted Manuscript published: February 16, 2021 (version 1)
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