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A Neural Circuit for the Suppression of Pain by a Competing Need State
Open accessAbstract
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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“It is also interesting to note that inflammatory pain is suppressed by activation of AgRP neurons, suggesting a general reduction of chronic pain perception by strong motivational drive states192.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [192]
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Metadata
- 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
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 173
- Issue
- 1
- Pages
- 140-152.e15
- ISSN
- 0092-8674 (ISSN-L)
- 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
- 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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