Evidence map›Paper›PMID 20101391›Full record

ArticlePsychopharmacology2010

Effects of kappa opioids in an assay of pain-depressed intracranial self-stimulation in rats.

S Stevens Negus, Ember M Morrissey, Marisa Rosenberg, K Cheng, Kenner C Rice

Abstract read
In one paragraph

Article in Psychopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
2.4field-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

51 citing papers in PubMed, 68 citations in OpenAlex.

  1. NOP agonist AT-403 promoted sleep in lactic acid-induced acute pain model.Frontiers in pain research (Lausanne, Switzerland) · 2025
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  10. Enhancement of Opioid Antinociception by Nicotinic Ligands.The Journal of pharmacology and experimental therapeutics · 2021
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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 2 institutions in 1 country.

S Stevens NegusDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA 23298, USA. ssnegus@vcu.edu
Ember M Morrissey
Marisa Rosenberg
K Cheng
Kenner C Rice
Virginia Commonwealth University · USNational Institutes of Health · US

Funding

Medicinal Chemistry of Drugs Acting on Central and Peripheral Opioid ReceptorsZIADA000527 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI RICE, KENNER · 2009 to 2025
$23.2M
Neurobiology and Treatment of PainR01NS070715 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI NEGUS, SIDNEY S, SELLEY, DANA E · 2009 to 2018
$3.3M
NOVEL DELTA OPIOIDS--ANALGESIC EFFECTS &ABUSE LIABILITYR01DA011460 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI NEGUS, SIDNEY S · 1999 to 2009
$1.9M
Intramural NIH HHSNIDA NIH HHS R01 DA011460NIDA NIH HHS R01-DA11460NINDS NIH HHS R01 NS070715NINDS NIH HHS R01-NS070715
6 · The paper itself

Abstract

rationaleSelective, centrally acting kappa opioid agonists produce antinociception in a wide range of preclinical assays, but these compounds perform poorly as analgesics in humans. This discrepancy may be related to the behavioral depressant effects of kappa agonists. Kappa antagonists do not typically produce antinociception, but they produce antidepressant-like effects in some preclinical assays.

objectiveThe objective of this study was to test the hypothesis that the kappa agonist U69,593 and the kappa antagonist norbinaltorphimine would produce pronociceptive and antinociceptive effects, respectively, in an assay of pain-depressed behavior.

methodsEffects of U69,593 (0.056-0.56 mg/kg), norbinaltorphimine (10-32 mg/kg), and morphine (3.2 mg/kg) were evaluated on the stimulation of a stretching response and the depression of intracranial self-stimulation (ICSS) of the medial forebrain bundle produced in rats by a common noxious stimulus (intraperitoneal administration of dilute lactic acid).

resultsU69,593 produced a dose-dependent blockade of acid-stimulated stretching but only exacerbated acid-induced depression of ICSS. Thus, U69,593 produced antinociception in the assay of pain-stimulated behavior but pronociceptive effects in the assay of pain-depressed behavior. Norbinaltorphimine did not alter acid-stimulated stretching or acid-induced depression of ICSS. The mu opioid agonist morphine blocked both acid-stimulated stretching and acid-induced depression of ICSS.

conclusionsThese results support the hypothesis that prodepressant effects of kappa agonists may limit their clinical utility as analgesics. These results do not support the use of kappa antagonists to treat depressant effects of pain. These findings illustrate the potential value of using complementary assays of pain-stimulated and pain-depressed behaviors for preclinical evaluation of candidate analgesics.

Indexed as

AnalgesicsAnalgesics, OpioidAnimalsBenzeneacetamidesDose-Response Relationship, DrugDrug Evaluation, PreclinicalLactic AcidMaleMedial Forebrain BundleMorphineNaltrexonePainPyrrolidinesRatsRats, Sprague-DawleyReceptors, Opioid, kappaAnalgesicsAnalgesics, OpioidBenzeneacetamidesLactic AcidMorphineNaltrexonenorbinaltorphiminePyrrolidinesReceptors, Opioid, kappaU 69593

Identifiers

PMID20101391
PMCPMC3156454
OpenAlexW1998777715

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.