Cited by 219Pain Mechanisms and TreatmentsRegulation of Appetite and ObesityNeuropeptides and Animal Physiology

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A Neural Circuit for the Suppression of Pain by a Competing Need State

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Alhadeff, Amber L., Su, Zhenwei, Hernandez, Elen, Klima, Michelle L., Phillips, Sophie Z., Holland, Ruby A., Guo, Caiying, Hantman, Adam W., De Jonghe, Bart C., Betley, J. Nicholas·2018·Cell

DOI 10.1016/j.cell.2018.02.057PMC PMC5877408

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Abstract

Hunger and pain are two competing signals that individuals must resolve to ensure survival. However, the neural processes that prioritize conflicting survival needs are poorly understood. We discovered that hunger attenuates behavioral responses and affective properties of inflammatory pain without altering acute nociceptive responses. This effect is centrally controlled, as activity in hunger-sensitive agouti-related protein (AgRP)-expressing neurons abrogates inflammatory pain. Systematic analysis of AgRP projection subpopulations revealed that the neural processing of hunger and inflammatory pain converge in the hindbrain parabrachial nucleus (PBN). Strikingly, activity in AgRP → PBN neurons blocked the behavioral response to inflammatory pain as effectively as hunger or analgesics. The anti-nociceptive effect of hunger is mediated by neuropeptide Y (NPY) signaling in the PBN. By investigating the intersection between hunger and pain, we have identified a neural circuit that mediates competing survival needs and uncovered NPY Y1 receptor signaling in the PBN as a target for pain suppression.

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Authors: Alhadeff, A. L., Su, Z., Hernandez, E., Klima, M. L., Phillips, S. Z., Holland, R. A., Guo, C., Hantman, A. W., De Jonghe, B. C., & Betley, J. N.
Affiliations: University of Pennsylvania (US)
Howard Hughes Medical Institute (US)
Corresponding author: Betley, J. Nicholas
ORCID: Alhadeff, Amber L.
Su, Zhenwei
Holland, Ruby A.
Hantman, Adam W.
Betley, J. Nicholas
Venue: Cell
Publisher: Elsevier BV
Published: 2018-03
Volume: 173
Issue: 1
Pages: 140-152.e15
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2018.02.057
PMC: PMC5877408
OpenAlex: W2789360989
Cited by: 218
References: 63
Citations by year: 2026: 27 · 2025: 24 · 2024: 22 · 2023: 27 · 2022: 27 · 2021: 34 · 2020: 20 · 2019: 21 · 2018: 15
FWCI: 15.43
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 386 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: University of Pennsylvania School of Arts and Sciences
American Heart Association (17SDG33400158)
Whitehall Foundation
NIH (1R01DK114104, 2T32DK7314-36, F32DK112561-01, R01DK114812)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: hunger, inflammatory pain, pain inhibition, parabrachial nucleus, neuropeptide Y, NPY Y1 receptor, neural circuits, analgesia, nociception, hindbrain
MeSH terms: Analgesics, Opioid, Animals, Anti-Inflammatory Agents, Non-Steroidal, Behavior, Animal, Diet, Feeding Behavior, Formaldehyde, Glutamate Decarboxylase, Locomotion, Mice, Inbred C57BL, Morphine, Neurons, Pain, Signal Transduction, Receptors, Neuropeptide Y, Mice, Agouti-Related Protein, Parabrachial Nucleus

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A Neural Circuit for the Suppression of Pain by a Competing Need State

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