Evidence map›Paper›PMID 30855519›Full record

ArticlePain2019

Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity.

Matthew R Sapio, Michael J Iadarola, Danielle M LaPaglia, Tanya Lehky, Audrey E Thurm, Kristen M Danley, Shannon R Fuhr, Mark D Lee, Amanda E Huey, Stephen J Sharp and 4 more

Open access · greenAbstract read
In one paragraph

Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

17 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. A compendium of validated pain genes.WIREs mechanisms of disease · 2022
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. A Role for Global DNA Methylation Level andFrontiers in pain research (Lausanne, Switzerland) · 2021
    Article
  14. The physiology of regulated BDNF release.Cell and tissue research · 2020
    Review
  15. Review
  16. Influences of UGT2B7 rs7439366 and rs12233719 Polymorphisms on Fentanyl Sensitivity in Chinese Gynecologic Patients.Medical science monitor : international medical journal of experimental and clinical research · 2020
    Article
  17. Article
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 7 institutions in 1 country.

Matthew R SapioDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States.
Michael J IadarolaDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States.
Danielle M LaPagliaDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States.
Tanya LehkyElectromyography Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, United States.
Audrey E ThurmPediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health (NIH), Bethesda, MD, United States.
Kristen M DanleyUnit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States.
Shannon R FuhrUnit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States.
Mark D LeeUnit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States.
Amanda E HueyUnit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, United States.
Stephen J SharpDepartent of Neurology, Uniformed Services University, Bethesda, MD, United States.
Jack W TsaoDepartent of Neurology, Uniformed Services University, Bethesda, MD, United States.
Jack A YanovskiSection on Growth and Obesity, NICHD, NIH, Bethesda, MD, United States.
Andrew J MannesDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States.
Joan C HanPediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health (NIH), Bethesda, MD, United States.
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Institutes of Health Clinical Center · USMemphis VA Medical Center · USNational Institute of Mental Health · USNational Institute of Neurological Disorders and Stroke · USPediatrics and Genetics · USUniformed Services University of the Health Sciences · US

Funding

Physiology, Psychology, and Genetics of ObesityZIAHD000641 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI YANOVSKI, JACK A. · 2009 to 2025
$24.8M
Neurodevelopmental and Behavioral Phenotyping ZICMH002961 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI THURM, AUDREY · 2017 to 2025
$12.6M
Integrative/Molecular Studies Of Pain And Pain ControlZ01DE000688 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI IADAROLA, MICHAEL J. · 1997 to 2008
$2.8M
Integrative And Molecular Studies Of Pain And Pain ControlZIACL090033 · CLC · CLINICAL CENTER · PI MANNES, ANDREW · 2014 to 2025
$0k
The Pain Neural TranscriptomeZIACL090035 · CLC · CLINICAL CENTER · PI MANNES, ANDREW · 2014 to 2025
$0k
Intramural NIH HHS Z01 DE000688Intramural NIH HHS Z99 HD999999Intramural NIH HHS ZIA HD000641
6 · The paper itself

Abstract

Rare pain-insensitive individuals offer unique insights into how pain circuits function and have led to the development of new strategies for pain control. We investigated pain sensitivity in humans with WAGR (Wilms tumor, aniridia, genitourinary anomaly, and range of intellectual disabilities) syndrome, who have variably sized heterozygous deletion of the 11p13 region. The deletion region can be inclusive or exclusive of the brain-derived neurotrophic factor (BDNF) gene, a crucial trophic factor for nociceptive afferents. Nociceptive responses assessed by quantitative sensory testing demonstrated reduced pain sensitivity only in the WAGR subjects whose deletion boundaries included the BDNF gene. Corresponding behavioral assessments were made in heterozygous Bdnf knockout rats to examine the specific role of Bdnf. These analogous experiments revealed impairment of Aδ- and C-fiber-mediated heat nociception, determined by acute nociceptive thermal stimuli, and in aversive behaviors evoked when the rats were placed on a hot plate. Similar results were obtained for C-fiber-mediated cold responses and cold avoidance on a cold-plate device. Together, these results suggested a blunted responsiveness to aversive stimuli. Our parallel observations in humans and rats show that hemizygous deletion of the BDNF gene reduces pain sensitivity and establishes BDNF as a determinant of nociceptive sensitivity.

Indexed as

AdolescentAdultAnimalsBrain-Derived Neurotrophic FactorChildFemaleGanglia, SpinalGene Expression ProfilingHumansHyperalgesiaLasersMaleMutationPainPain MeasurementPain ThresholdBrain-Derived Neurotrophic Factor

Identifiers

PMID30855519
PMCPMC6476691
OpenAlexW2921321622

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.