Evidence map›Paper›PMID 40260913›Full record

ArticleJCI insight2025

A small molecule PKCε inhibitor reduces hyperalgesia induced by paclitaxel or opioid withdrawal.

Adriana Gregory-Flores, Ivan Jm Bonet, Stève Desaivre, Jon D Levine, Stanton F McHardy, Harmannus C de Kraker, Nicholas A Clanton, Peter M LoCoco, Nicholas M Russell, Caleb Fleischer and 2 more

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

12 authors.

Adriana Gregory-FloresInstitute for Neuroscience and.
Ivan Jm BonetDepartment of Oral and Maxillofacial Surgery, UCSF Pain and Addiction Research Center, and.
Stève DesaivreDepartment of Neuroscience and the Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas, USA.
Jon D LevineDepartment of Oral and Maxillofacial Surgery, UCSF Pain and Addiction Research Center, and.
Stanton F McHardyDepartment of Chemistry, Center for Innovative Drug Discovery, and.
Harmannus C de KrakerDepartment of Chemistry, Center for Innovative Drug Discovery, and.
Nicholas A ClantonVoelcker Preclinical Pharmacology Core, Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas, USA.
Peter M LoCocoVoelcker Preclinical Pharmacology Core, Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas, USA.
Nicholas M RussellDivision of Pharmacology and Toxicology, College of Pharmacy.
Caleb FleischerDepartment of Neuroscience and the Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas, USA.
Robert O MessingInstitute for Neuroscience and.
Michela MarinelliInstitute for Neuroscience and.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The enzyme protein kinase C ε (PKCε) plays an important role in pain signaling and represents a promising therapeutic target for the treatment of chronic pain. We designed and generated a small molecule inhibitor of PKCε, CP612, and examined its effect in a rodent model of chemotherapy-induced neuropathic pain produced by paclitaxel, which does not respond well to current therapeutics. In addition, many patients with chronic pain use opiates, which over time can become ineffective, and attempts to discontinue them can increase pain thereby promoting sustained opioid use. Therefore, we also investigated if CP612 alters pain due to opioid withdrawal. We found that CP612 attenuated hyperalgesia produced by paclitaxel, and it both prevented and reversed hyperalgesia induced by opioid withdrawal. It was not self-administered and did not affect morphine self-administration. These findings suggest that inhibition of PKCε is an effective, nonaddictive strategy to treat chemotherapy-induced neuropathic pain, with the added benefit of preventing increases in pain that occur as opioid treatment is discontinued. This latter property could benefit individuals with chronic pain who find it difficult to discontinue opioids.

Indexed as

Analgesics, OpioidHyperalgesiaNeuralgiaPaclitaxelProtein Kinase C-epsilonProtein Kinase InhibitorsSubstance Withdrawal SyndromeAnimalsDisease Models, AnimalMaleMorphineRatsRats, Sprague-DawleyAnalgesics, OpioidMorphinePaclitaxelProtein Kinase C-epsilonProtein Kinase InhibitorsAddictionNeurosciencePainProtein kinasesTherapeutics

Identifiers

PMID40260913
PMCPMC12016938

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.