Evidence map›Paper›PMID 29049116›Full record

ReviewAnesthesia and analgesia2017

Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics.

Nebojsa Nick Knezevic, Ajay Yekkirala, Tony L Yaksh

Open access · greenAbstract readReview
In one paragraph

Review in Anesthesia and analgesia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

20 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Discovery and development of an oral analgesic targeting the α2B adrenoceptor.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Review
  6. Article
  7. Article
  8. Subjects suffering from bipolar disorder taking lithium are less likely to report physical pain: a FACE-BD study.European psychiatry : the journal of the Association of European Psychiatrists · 2023
    Article
  9. Article
  10. Mechanisms of Transmission and Processing of Pain: A Narrative Review.International journal of environmental research and public health · 2023
    Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Opioid Tolerance in Critical Illness.The New England journal of medicine · 2019
    Review
  18. Article
  19. Article
  20. Review
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

3 authors at 2 institutions in 1 country.

Nebojsa Nick KnezevicFrom the *Department of Anesthesiology, Advocate Illinois Masonic Medical Center Chicago, Illinois; Departments of †Anesthesiology and ‡Surgery, University of Illinois, Chicago, Illinois; §Department of Neurobiology, Harvard Medical School, and Boston Children's Hospital, Boston, Massachusetts; ‖Blue Therapeutics, Harvard Innovation Launch Lab, Allston, Massachusetts; and Departments of ¶Anesthesiology and #Pharmacology, University of California, San Diego, La Jolla, California.
Ajay Yekkirala
Tony L Yaksh
Boston Children's Hospital · USUniversity of Illinois Chicago · US

Funding

Development of a non-addictive analgesic targeting opioid receptor heteromers.R44DA041912 · NIDA · BLUE THERAPEUTICS, INC. · PI YEKKIRALA, AJAY S · 2016 to 2020
$4.7M
Characterization of Toxicity with Spinal OpiatesR01DA015353 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YAKSH, TONY L. · 2003 to 2017
$4.4M
Sex, Stress and Immunity in the Acute to Chronic Pain TransitionR01NS099338 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YAKSH, TONY L. · 2017 to 2021
$1.8M
NIDA NIH HHS R01 DA015353NIDA NIH HHS R44 DA041912NINDS NIH HHS R01 NS099338
6 · The paper itself

Abstract

Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management has limitations, and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of reinforcing activity in the absence of a pain state. The present work provides a nonexclusive overview of current drug targets and potential future directions of research and development. We discuss channel activators and blockers, including sodium channel blockers, potassium channel activators, and calcium channel blockers; glutamate receptor-targeted agents, including N-methyl-D-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, and metabotropic receptors. Furthermore, we discuss therapeutics targeted at γ-aminobutyric acid, α2-adrenergic, and opioid receptors. We also considered antagonists of angiotensin 2 and Toll receptors and agonists/antagonists of adenosine, purine receptors, and cannabinoids. Novel targets considered are those focusing on lipid mediators and anti-inflammatory cytokines. Of interest is development of novel targeting strategies, which produce long-term alterations in pain signaling, including viral transfection and toxins. We consider issues in the development of druggable molecules, including preclinical screening. While there are examples of successful translation, mechanistically promising preclinical candidates may unexpectedly fail during clinical trials because the preclinical models may not recapitulate the particular human pain condition being addressed. Molecular target characterization can diminish the disconnect between preclinical and humans' targets, which should assist in developing nonaddictive analgesics.

Indexed as

Analgesics, Non-NarcoticAnalgesics, OpioidAnimalsDrug CompoundingDrug DiscoveryHumansMolecular Targeted TherapyOpioid-Related DisordersPainPain PerceptionPain ThresholdPhenotypeRisk FactorsSignal TransductionTranslational Research, BiomedicalAnalgesics, Non-NarcoticAnalgesics, Opioid

Identifiers

PMID29049116
PMCPMC5679134
OpenAlexW2765534312

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.