Evidence map›Paper›PMID 30422869›Full record

ArticlePain2019

Decitabine attenuates nociceptive behavior in a murine model of bone cancer pain.

Camilla Kristine Appel, Nicole Newell Scheff, Chi Tonglien Viet, Brian Lee Schmidt, Anne-Marie Heegaard

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 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Epigenetic Landscapes of Pain: DNA Methylation Dynamics in Chronic Pain.International journal of molecular sciences · 2024
    Review
  2. Article
  3. Article
  4. Frontiers in oncology · 2021
    Review
  5. Article
  6. Article
  7. Review
  8. 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

5 authors at 3 institutions in 2 countries.

Camilla Kristine AppelFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nicole Newell ScheffBluestone Center for Clinical Research, New York University, New York, NY, United States.
Chi Tonglien VietBluestone Center for Clinical Research, New York University, New York, NY, United States.
Brian Lee SchmidtBluestone Center for Clinical Research, New York University, New York, NY, United States.
Anne-Marie HeegaardFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Center for Clinical Research (United States) · USUniversity of Copenhagen · DKNew York University · US

Funding

Non-viral gene therapy for cancer painR01DE025393 · NIDCR · NEW YORK UNIVERSITY · PI SCHMIDT, BRIAN L, YAMANO, SEIICHI · 2016 to 2018
$1.3M
NIDCR NIH HHS R01 DE025393
6 · The paper itself

Abstract

Bone cancer metastasis is extremely painful and decreases the quality of life of the affected patients. Available pharmacological treatments are not able to sufficiently ameliorate the pain, and as patients with cancer are living longer, new treatments for pain management are needed. Decitabine (5-aza-2'-deoxycytidine), a DNA methyltransferases inhibitor, has analgesic properties in preclinical models of postsurgical and soft-tissue oral cancer pain by inducing an upregulation of endogenous opioids. In this study, we report that daily treatment with decitabine (2 µg/g, intraperitoneally) attenuated nociceptive behavior in the 4T1-luc2 mouse model of bone cancer pain. We hypothesized that the analgesic mechanism of decitabine involved activation of the endogenous opioid system through demethylation and reexpression of the transcriptionally silenced endothelin B receptor gene, Ednrb. Indeed, Ednrb was hypermethylated and transcriptionally silenced in the mouse model of bone cancer pain. We demonstrated that expression of Ednrb in the cancer cells lead to release of β-endorphin in the cell supernatant, which reduced the number of responsive dorsal root ganglia neurons in an opioid-dependent manner. Our study supports a role of demethylating drugs, such as decitabine, as unique pharmacological agents targeting the pain in the cancer microenvironment.

Indexed as

AnimalsAntimetabolites, Antineoplasticbeta-EndorphinBone DensityBone NeoplasmsCancer PainCell Line, TumorCulture Media, ConditionedDecitabineDisease Models, AnimalEndothelin-1FemaleGanglia, SpinalLocomotionMiceMice, Inbred BALB CAntimetabolites, Antineoplasticbeta-EndorphinCulture Media, ConditionedDecitabineEDNRB protein, mouseEndothelin-1NaloxoneN-methylnaloxoneQuaternary Ammonium CompoundsReceptor, Endothelin B

Identifiers

PMID30422869
PMCPMC6377317
OpenAlexW2901980459

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.