Evidence map›Paper›PMID 34663957›Full record

ArticleNature neuroscience2021

Pain induces adaptations in ventral tegmental area dopamine neurons to drive anhedonia-like behavior.

Tamara Markovic, Christian E Pedersen, Nicolas Massaly, Yvan M Vachez, Brian Ruyle, Caitlin A Murphy, Kavitha Abiraman, Jung Hoon Shin, Jeniffer J Garcia, Hye Jean Yoon and 4 more

Open access · greenAbstract read
In one paragraph

Article in Nature neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
8.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 125 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Prelimbic cortical excitatory overdrive and inhibitory underdrive accompany environmental suppression of food seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  17. Inflammatory pain in mice induces light cycle-dependent effects on sleep architecture.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  18. Article
  19. Article
  20. Article

16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Tamara MarkovicDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA.
Christian E PedersenCenter for the Neurobiology of Addiction, Pain and Emotion, Departments of Anesthesiology and Pharmacology, University of Washington, Seattle, WA, USA.
Nicolas MassalyDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA.
Yvan M VachezDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA.
Brian RuyleDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-8507-8218
Caitlin A MurphyDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA.
Kavitha AbiramanDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA.
Jung Hoon ShinLaboratory on Neurobiology of Compulsive Behaviors, National Institute on Alcohol Abuse and Alcoholism, Center on Compulsive Behaviors, Intramural Research Program, NIH, Bethesda, MD, USA.
Jeniffer J GarciaSchool of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Hye Jean YoonDepartment of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-3830-3678
Veronica A AlvarezLaboratory on Neurobiology of Compulsive Behaviors, National Institute on Alcohol Abuse and Alcoholism, Center on Compulsive Behaviors, Intramural Research Program, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2611-8675
Michael R BruchasCenter for the Neurobiology of Addiction, Pain and Emotion, Departments of Anesthesiology and Pharmacology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-4713-7816
Meaghan C Creed *Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA. meaghan.creed@wustl.edu.ORCID http://orcid.org/0000-0002-9658-2601
Jose A Morón *Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA. jmoron-concepcion@wustl.edu.ORCID http://orcid.org/0000-0003-3216-2488
Washington University in St. Louis · USNational Institute on Alcohol Abuse and Alcoholism · USUniversity of Washington · US

Funding

Dissecting circuits mediating pain-induced alterations in motivated behaviorR01DA041781 · NIDA · WASHINGTON UNIVERSITY · PI MORON-CONCEPCION, JOSE A · 2017 to 2021
$2.3M
Dissecting the role of ventral pallidal projections to nucleus accumbens in reward processingR01DA049924 · NIDA · WASHINGTON UNIVERSITY · PI CREED, MEAGHAN C · 2020 to 2024
$2.0M
Role of SK2 channels in morphine dependenceR01DA042499 · NIDA · WASHINGTON UNIVERSITY · PI MORON-CONCEPCION, JOSE A · 2017 to 2021
$1.9M
Defining a role for kappa opioid system in affective behavior and drug escalation in painR01DA045463 · NIDA · WASHINGTON UNIVERSITY · PI MORON-CONCEPCION, JOSE A · 2018 to 2022
$1.8M
USING TRANSGENIC MICE TO EXAMINE THE ROLE OF CNIH3 VARIANTS IN OPIOID DEPENDENCER33DA041883 · NIDA · WASHINGTON UNIVERSITY · PI DOUGHERTY, JOSEPH D, MORON-CONCEPCION, JOSE A · 2018 to 2020
$1.1M
In vivo imaging of dynamic structural plasticity driving morphine conditioned place preferenceR21DA042581 · NIDA · WASHINGTON UNIVERSITY · PI HAN, EDWARD BING, MORON-CONCEPCION, JOSE A · 2016 to 2017
$381k
USING TRANSGENIC MICE TO EXAMINE THE ROLE OF CNIH3 VARIANTS IN OPIOID DEPENDENCER21DA041883 · NIDA · WASHINGTON UNIVERSITY · PI DOUGHERTY, JOSEPH D, MORON-CONCEPCION, JOSE A · 2016 to 2017
$379k
A novel deep brain stimulation protocol to prevent relapse driven by negative reinforcementR21DA047127 · NIDA · WASHINGTON UNIVERSITY · PI CREED, MEAGHAN C · 2018 to 2019
$352k
Reward Value Encoding of Dynorphin and Enkephalin Neurons in Medial Accumbens ShellF31DA051124 · NIDA · UNIVERSITY OF WASHINGTON · PI PEDERSEN, CHRISTIAN · 2020 to 2020
$38k
NIDA NIH HHS F31 DA051124NIDA NIH HHS R01 DA041781NIDA NIH HHS R01 DA042499NIDA NIH HHS R01 DA045463NIDA NIH HHS R01 DA049924NIDA NIH HHS R21 DA041883NIDA NIH HHS R21 DA042581NIDA NIH HHS R21 DA047127NIDA NIH HHS R33 DA041883
6 · The paper itself

Abstract

The persistence of negative affect in pain leads to co-morbid symptoms such as anhedonia and depression-major health issues in the United States. The neuronal circuitry and contribution of specific cellular populations underlying these behavioral adaptations remains unknown. A common characteristic of negative affect is a decrease in motivation to initiate and complete goal-directed behavior, known as anhedonia. We report that in rodents, inflammatory pain decreased the activity of ventral tegmental area (VTA) dopamine (DA) neurons, which are critical mediators of motivational states. Pain increased rostromedial tegmental nucleus inhibitory tone onto VTA DA neurons, making them less excitable. Furthermore, the decreased activity of DA neurons was associated with reduced motivation for natural rewards, consistent with anhedonia-like behavior. Selective activation of VTA DA neurons was sufficient to restore baseline motivation and hedonic responses to natural rewards. These findings reveal pain-induced adaptations within VTA DA neurons that underlie anhedonia-like behavior.

Indexed as

Adaptation, PhysiologicalAnhedoniaAnimalsConditioning, OperantDopaminergic NeuronsFemaleMaleOptogeneticsPainRatsRats, Long-EvansRats, TransgenicVentral Tegmental Area

Identifiers

PMID34663957
PMCPMC8556343
OpenAlexW3207767877

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.