Evidence map›Paper›PMID 39542192›Full record

ArticleThe journal of pain2025

Peripherally mediated opioid combination therapy in mouse and pig.

C D Peterson, C M Larson, D J Bruce, B M Clements, K R Pflepsen, E Akgün, K F Kitto, M M Lunzer, C A Fairbanks, P S Portoghese and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

11 authors.

C D PetersonDepartment of Pharmaceutics, University of Minnesota College of Pharmacy, USA; Department of Neuroscience, University of Minnesota Medical School, USA; Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, USA. Electronic address: pete6187@umn.edu.
C M LarsonComparative and Molecular Biosciences, University of Minnesota College of Veterinary Medicine, USA.
D J BruceDepartment of Neuroscience, University of Minnesota Medical School, USA; Department of Pharmacology, University of Minnesota Medical School, USA.
B M ClementsDepartment of Pharmaceutics, University of Minnesota College of Pharmacy, USA.
K R PflepsenDepartment of Pharmaceutics, University of Minnesota College of Pharmacy, USA.
E AkgünDepartment of Medicinal Chemistry, University of Minnesota College of Pharmacy, USA.
K F KittoDepartment of Neuroscience, University of Minnesota Medical School, USA.
M M LunzerDepartment of Medicinal Chemistry, University of Minnesota College of Pharmacy, USA.
C A FairbanksDepartment of Pharmaceutics, University of Minnesota College of Pharmacy, USA; Department of Neuroscience, University of Minnesota Medical School, USA; Department of Pharmacology, University of Minnesota Medical School, USA.
P S PortogheseDepartment of Medicinal Chemistry, University of Minnesota College of Pharmacy, USA.
G L WilcoxDepartment of Neuroscience, University of Minnesota Medical School, USA; Department of Pharmacology, University of Minnesota Medical School, USA; Department of Dermatology, University of Minnesota Medical School, USA.

Funding

Training in PharmacoNeuroImmune Substance Abuse ResearchT32DA007097 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MOLITOR, THOMAS WILLIAM · 1985 to 2021
$13.1M
NEUROSCIENCE TRAINING IN DRUG ABUSE RESEARCHT32DA007234 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Paul G Mermelstein, Jocelyn M Richard · 1986 to 2026
$10.9M
Comparative Medicine and Pathology TrainingT32OD010993 · OD · UNIVERSITY OF MINNESOTA · PI DAVID R BROWN, Cathy S. Carlson · 2012 to 2026
$6.2M
Mechanisms of Opioid Receptor InteractionsR01DA015438 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI WILCOX, GEORGE LATIMER · 2004 to 2014
$3.3M
MIN-REACH Research Evaluation and Commercialization HubU01HL127479 · NHLBI · UNIVERSITY OF MINNESOTA · PI GURVICH, VADIM J., HUBEL, ALLISON · 2015 to 2017
$3.0M
NHLBI NIH HHS U01 HL127479NIDA NIH HHS R01 DA015438NIDA NIH HHS T32 DA007097NIDA NIH HHS T32 DA007234NIH HHS T32 OD010993
6 · The paper itself

Abstract

The concomitant epidemics of chronic pain and opioid misuse in the United States have led to a call for novel analgesics with limited abuse potential. Previously, we have shown that co-delivery of a novel combination targeting both μ- and δ-opioid receptors in the peripheral and central nervous systems can produce synergistic analgesia. Loperamide, a peripherally restricted μ-opioid agonist, and oxymorphindole, a δ-opioid receptor partial agonist, synergize in multiple mouse models of hyperalgesia. We predicted this effect would generalize across species and therefore assessed this combination for analgesic synergy in a mouse model of post-incisional hypersensitivity. In mice, oxymorphindole and loperamide displayed significant analgesic synergy. Similar synergy was observed with N-benzyl-oxymorphindole and loperamide. In cross-bred pigs, we compared the analgesic effects of either morphine alone or the combination of oxymorphindole and loperamide or the combination of N-benzyl-oxymorphindole and loperamide. Both combinations showed increased potency as compared to morphine sulfate and effectively reduced hypersensitivity following injury without side effects. From these data we conclude that the combination of oxymorphindole and loperamide or the combination of N-benzyl-oxymorphindole and loperamide reverse incisional hyperalgesia, likely by acting in the periphery, in a large animal model without adverse effects on respiration or heart rate. PERSPECTIVE: This article presents novel opioid combinations, the μ-opioid agonist loperamide with a δ-opioid agonist, either oxymorphindole (OMI) or N-benzyl-oxymorphindole (BOMI), that relieve pain in mice and pigs without adverse side effects. These therapies could help clinicians manage pain in patients while reducing overall opioid burden and limiting side effects.

Indexed as

Analgesics, OpioidHyperalgesiaLoperamideAnimalsDisease Models, AnimalDrug SynergismDrug Therapy, CombinationFemaleMaleMiceMice, Inbred C57BLMorphineReceptors, Opioid, deltaReceptors, Opioid, muSwineAnalgesics, OpioidLoperamideMorphineReceptors, Opioid, deltaReceptors, Opioid, muAnalgesiaCombination synergyLoperamideOxymorphindolePig model

Identifiers

PMID39542192
PMCPMC11807752

What OpenQuestion holds

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Registered trials

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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.