A parabrachial hub for need-state control of enduring pain
Long-term sustained pain following acute physical injury is a prominent feature of chronic pain conditions<sup>1</sup>. Populations of neurons that rapidly respond to noxious stimuli or tissue damage have been identified in the spinal cord and several nuclei in the brain<sup>2-4</sup>. Understanding the central mechanisms that signal ongoing sustained pain, including after tissue healing, remains a challenge<sup>5</sup>. Here we use spatial transcriptomics, neural manipulations, activity recordings and computational modelling to demonstrate that activity in an ensemble of anatomically and molecularly diverse parabrachial neurons that express the neuropeptide Y (NPY) receptor Y1 (Y1R neurons) is increased following injury and predicts functional coping behaviour. Hunger, thirst or predator cues suppressed sustained pain, regardless of the injury type, by inhibiting parabrachial Y1R neurons via the release of NPY. Together, our results demonstrate an endogenous analgesic hub at pain-responsive parabrachial Y1R neurons.
Authors
- Yasmina Dumiaty (ORCID: https://orcid.org/0000-0003-1784-9361)
- Kayla A. Kruger
- Melissa J. Chee (ORCID: https://orcid.org/0000-0003-3815-9095)
- Rajesh Khanna (ORCID: https://orcid.org/0000-0002-9066-2969)
- Nicholas K. Smith (ORCID: https://orcid.org/0000-0002-3724-4522)
- Albert T. M. Yeung
- Nitsan Goldstein (ORCID: https://orcid.org/0000-0003-0926-5366)
- Heather N. Allen (ORCID: https://orcid.org/0000-0003-0771-1959)
- Edward Chin Man Lo (ORCID: https://orcid.org/0000-0002-3618-0619)
- Amadeus Maes (ORCID: https://orcid.org/0000-0002-4475-9727)
- J. Nicholas Betley (ORCID: https://orcid.org/0000-0002-4014-9147)
- Tyler S. Nelson (ORCID: https://orcid.org/0000-0002-6675-4820)
- Christoph A. Thaiss (ORCID: https://orcid.org/0000-0001-8226-7718)
- Niklas Blank (ORCID: https://orcid.org/0000-0001-9794-3547)
- Ann Kennedy (ORCID: https://orcid.org/0000-0002-3782-0518)
- Morgan Kindel (ORCID: https://orcid.org/0000-0001-6040-3862)
- Bradley K. Taylor (ORCID: https://orcid.org/0000-0002-5080-6120)
- Jamie R. E. Carty (ORCID: https://orcid.org/0000-0003-2588-3471)
- Erin L. Marble
- Rachael E. Villari
- Lavinia Boccia
- Ella Cho
- Michelle Awh
Institutions
- Scripps Research Institute (US)
- University of Pittsburgh (US)
- University of Florida (US)
- Palo Alto Institute (US)
- Arc Research Institute
- Carleton University (CA)
- University of Pennsylvania (US)
- Philadelphia University (US)
- Stanford University (US)
Publication Details
- Journal
- Nature
- Published
- 2025-10-08
- DOI
- https://doi.org/10.1038/s41586-025-09602-x
- Citations
- 10
- Primary Topic
- Pain Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 11.64