Evidence map›Paper›PMID 42390819›Full record

ArticlePsychopharmacology2026

Effects of repeated treatment with opioids that vary in mu opioid receptor efficacy on pain-depressed locomotor behavior in mice.

Jawaun Harris, Dana R Chambers, Delmis E Hernandez, Arthur E Jacobson, Joshua A Lutz, Kenner C Rice, Agnieszka Sulima, S Stevens Negus

Abstract read
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In one paragraph

Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Jawaun HarrisDepartment of Pharmacology & Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Dana R ChambersDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, NIDA and NIAAA, Bethesda, USA.
Delmis E HernandezDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, NIDA and NIAAA, Bethesda, USA.
Arthur E JacobsonDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, NIDA and NIAAA, Bethesda, USA.
Joshua A LutzDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, NIDA and NIAAA, Bethesda, USA.
Kenner C RiceDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, NIDA and NIAAA, Bethesda, USA.
Agnieszka SulimaDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, NIDA and NIAAA, Bethesda, USA.
S Stevens NegusDepartment of Pharmacology & Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA. ssnegus@vcu.edu.

Funding

VCU Center for Drug Addiction ResearchP30DA033934 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI JOLENE J WINDLE · 2014 to 2026
$13.8M
Virginia Commonwealth University Postbaccalaureate Research Education ProgramR25GM089614 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI Rebecca Kelley Martin · 2010 to 2026
$4.9M
NIDA NIH HHS P30DA033934NIGMS NIH HHS R25GM089614
6 · The paper itself

Abstract

rationaleMu opioid receptor (MOR) analgesics like morphine have high intrinsic MOR efficacy but produce side effects. Lower efficacy MOR agonists like buprenorphine can produce analgesia with improved safety. We recently described a series of novel phenylmorphan-based MOR agonists with graded MOR efficacies, including several with sub-buprenorphine efficacies, and we described their acute effectiveness in mice to produce (a) antinociception in an assay of pain-related locomotor depression, and (b) improved safety on a range of side effects. Effects of repeated treatment with these compounds have not been examined.

objectiveThe present objective was to compare effects of repeated treatment with four opioids that ranged from high to low MOR efficacy (morphine> buprenorphine > JL-2-39 > DC-1-76.1).

methodsFemale and male ICR mice were treated once daily for 7 days with a selected dose of each drug ± intraperitoneal lactic acid (IP acid) as a noxious stimulus and evaluated for vertical and horizontal locomotor activity on Days 1 and 7.

resultsIP acid alone produced sustained, concentration-dependent, and pain-related locomotor depression. When administered as a daily pretreatment to IP acid, all four opioids produced sustained antinociception expressed as significant alleviation of IP acid-induced behavioral depression on Days 1 and 7. However, when these opioids were administered alone, effects were efficacy dependent. Morphine produced locomotor stimulation and sensitization; buprenorphine and JL-2-39 produced locomotor stimulation without sensitization; DC-1-76.1 produced neither stimulation or sensitization.

conclusionsThese findings support continued consideration of low-efficacy MOR agonists as candidate analgesics that can produce sustained antinociception with reduced side effects during repeated treatment.

Indexed as

Chronic treatmentEfficacyMorphineMu opioid receptor agonistPain-depressed behaviorSensitizationTolerance

Identifiers

PMID42390819

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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.