A spinoparabrachial circuit defined by Tacr1 expression drives pain
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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.
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The mid excitatory (ME)/Lmx1b family comprised Excit-21, Excit-22, Excit-23, Excit-24, and Excit-25 and corresponds to cells suggested to be involved in pain.
“The mid excitatory (ME)/Lmx1b family was comprised of Excit-21, Excit-22, Excit-23, Excit-24, and Excit-25 and corresponds to cells suggested to be involved in pain3,83.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [83]
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Identification of a convergent spinal neuron population that encodes itchPreprint
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Characterization of direct Purkinje cell outputs to the brainstemPreprint
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A Tac1 ‐Expressing Brainstem Pathway Underlies the Pathogenesis of Trigeminal Neuralgia
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Brainstem sensing of multiple body signals during food consumption
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- Authors
- Barik, A., Sathyamurthy, A., Thompson, J., Seltzer, M., Levine, A., & Chesler, A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Chesler, Alexander
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2021-02-16
- Volume
- 10
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC7993995
- OpenAlex
- W3130795191
- Cited by
- 93
- References
- 53
- Citations by year
- 2026: 22 · 2025: 17 · 2024: 25 · 2023: 9 · 2022: 14 · 2021: 5 · 2020: 1
- FWCI
- 8.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Center for Complementary and Integrative Health (Intramural program)
- National Institute of Neurological Disorders and Stroke (Intramural program)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- neurokinin-1 receptor, nocifensive behavior, ongoing pain, nociception
- MeSH terms
- Animals, Interneurons, Mice, Transgenic, Neural Pathways, Neurons, Pain, Pruritus, Touch, Tachykinins, Parabrachial Nucleus
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