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 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.

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All data generated or analysed during this study are included in the manuscript and supporting files. Source data have been uploaded

Article and author information

Author details

  1. Arnab Barik

    National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6850-0894
  2. Anupama Sathyamurthy

    National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. James H Thompson

    National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Mathew Seltzer

    National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ariel J Levine

    NINDS, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0335-0730
  6. Alexander Theodore Chesler

    National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, United States
    For correspondence
    alexander.chesler@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3131-0728

Funding

National Center for Complementary and Integrative Health (Intramural program)

  • Alexander Theodore Chesler

National Institute of Neurological Disorders and Stroke (Intramural program)

  • Ariel J Levine

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

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).

Reviewing Editor

  1. Allan Basbaum, University of California San Francisco, United States

Publication history

  1. Received: July 16, 2020
  2. Accepted: February 15, 2021
  3. Accepted Manuscript published: February 16, 2021 (version 1)
  4. Version of Record published: March 25, 2021 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Arnab Barik
  2. Anupama Sathyamurthy
  3. James H Thompson
  4. Mathew Seltzer
  5. Ariel J Levine
  6. Alexander Theodore Chesler
(2021)
A spinoparabrachial circuit defined by Tacr1 expression drives pain
eLife 10:e61135.
https://doi.org/10.7554/eLife.61135

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