Evidence map›Paper›PMID 40823889›Full record

ArticleMolecular pain

CB2 receptor agonist AM1241 regulating the polarization of microglia reduces morphine tolerance through IL-4/STAT6 pathway.

Di Cui, Yuanyuan Zhang, Chuhua Yang, Qingling Kong, Guonian Wang, Mingyue Zhang

Abstract read
In one paragraph

Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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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

6 authors.

Di CuiDepartment of Anesthesiology, 3201 Hospital, Hanzhong, China.ORCID 0009-0007-9686-3001
Yuanyuan ZhangDepartment of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China.ORCID 0009-0004-8687-8291
Chuhua YangDepartment of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China.ORCID 0009-0006-8971-350X
Qingling KongDepartment of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China.ORCID 0009-0001-6022-7747
Guonian WangDepartment of Anesthesiology, The Fourth Hospital of Harbin Medical University, Harbin, China.ORCID 0000-0002-5525-9939
Mingyue ZhangDepartment of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China.ORCID 0009-0004-8687-8291

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPain seriously impacts patients' life quality. The use of morphine for pain is common, but tolerance limits its application in clinic. However, there is no exact mechanism for tolerance. In this study, we explored how microglial polarization and IL (interleukin)-4,along with a CB2 receptor agonist, affect reducing morphine tolerance.

methodThe cells cultivated with morphine or combined CB2R agonist AM1241, CB2R antagonist AM630, CB1R antagonist AM281, and IL-4 inhibitor (IL-4I).Mice were injected with these drugs for 7 days, and hot plate behavioral tests were performed 30 min after administration respectively. Mice received a single morphine injection on day 8.Samples were taken post-tests. The expression of iNOS, SOCS3, IL-4 and STAT6 mRNA were detected by qPCR; the expression of iNOS, SOCS3, p-STAT6 and STAT6 protein were detected by Western blot. Inflammatory cytokines were detected with Elisa kit.

resultsThe M1 marker iNOS increased, the M2 marker SOCS3 decreased, p-STAT6 protein did not change, and the cytokines increased after morphine treatment. The paw withdrawal latency (PWL) value, IL-4 mRNA and p-STAT6 protein increased after AM1241 treatment, iNOS decreased and SOCS3 increased after AM1241 treatment, AM1241 decreased the pro-inflammatory cytokines, increased IL-4, IL-10 secretion. AM630 and IL-4I reversed the effect of AM1241 on PWL, M1 M2 markers.

conclusionThe polarization of microglia in the direction of M1 caused morphine tolerance, AM1241 increased the IL-4 mRNA and induced the phosphorylation protein of STAT6 to reduce the tolerance, and AM1241 induced microglia to polarization in the direction of M2. AM1241 regulated microglia polarization through IL-4/STAT6 pathway, thereby reducing tolerance.

Indexed as

Cell PolarityDrug ToleranceInterleukin-4MicrogliaMorphineReceptor, Cannabinoid, CB2Signal TransductionSTAT6 Transcription FactorAnimalsMaleMiceMice, Inbred C57BLNitric Oxide Synthase Type IIInterleukin-4MorphineNitric Oxide Synthase Type IIReceptor, Cannabinoid, CB2Stat6 protein, mouseSTAT6 Transcription FactorCannabinoid type 2 receptorinflammatory cytokinesmicroglial polarizationmorphine tolerance

Identifiers

PMID40823889
PMCPMC12484903

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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.