Evidence mapPaperPMID 39356320Full record

ArticleNaunyn-Schmiedeberg's archives of pharmacology2025

Sex differences in the orofacial antinociceptive effect of metformin and the role of transient receptor potential channels.

Sacha Aubrey Alves Rodrigues Santos, Marina de Barros Mamede Vidal Damasceno, Barry John Sessle, Antônio Eufrásio Vieira-Neto, Gerlânia de Oliveira Leite, Francisco Ernani Alves Magalhães, Kaio César Simiano Tavares, Samara Casemiro Benevides, Adriana Rolim Campos

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Article in Naunyn-Schmiedeberg's archives of pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
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 synthesis or guideline pooled it.

  1. Pooled it
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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

9 authors.

Sacha Aubrey Alves Rodrigues SantosExperimental Biology Center, University of Fortaleza, Fortaleza, Brazil.
Marina de Barros Mamede Vidal DamascenoExperimental Biology Center, University of Fortaleza, Fortaleza, Brazil.
Barry John SessleDepartment of Physiology and Faculty of Dentistry, University of Toronto, Toronto, Canada.
Antônio Eufrásio Vieira-NetoExperimental Biology Center, University of Fortaleza, Fortaleza, Brazil.
Gerlânia de Oliveira LeiteExperimental Biology Center, University of Fortaleza, Fortaleza, Brazil.
Francisco Ernani Alves MagalhãesExperimental Biology Center, University of Fortaleza, Fortaleza, Brazil.
Kaio César Simiano TavaresExperimental Biology Center, University of Fortaleza, Fortaleza, Brazil.
Samara Casemiro BenevidesExperimental Biology Center, University of Fortaleza, Fortaleza, Brazil.
Adriana Rolim CamposExperimental Biology Center, University of Fortaleza, Fortaleza, Brazil. adrirolim@unifor.br.

Funding

Edson Queiroz Foundation #49/2019UNIFOR Global Research Fellowship Award #PS00283112
6 · The paper itself

Abstract

Metformin is classified as a biguanide and is used in the treatment of type 2 diabetes. It is used worldwide and has been investigated in drug repositioning. The present study aims to investigate whether there is sexual dimorphism in the orofacial antinociceptive effect of metformin and the participation of TRP channels. Acute nociceptive behavior was induced by administering cinnamaldehyde or capsaicin to the upper lip. Nociceptive behavior was assessed through orofacial rubbing, and the effects of pre-treatment with metformin (125 or 250 mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The chronic pain model involved infraorbital nerve transection (IONX) was evaluated using Von Frey electronic filaments. Trpv1 gene expression was analyzed in the nerve ganglion. Docking experiments were performed. Metformin, but not the vehicle, produced antinociception (p < 0.0001) in all acute nociceptive behaviors in both sexes, and these effects were attenuated by the TRPV1 antagonist capsazepine and the TRPA1 antagonist HC-030031. In IONX with better (**p < 0.01, ****p < 0.0001 vs. control) results in females. TRPV1 gene expression was observed in the metformin treated group (*p < 0.05 vs. control). Docking experiments revealed that metformin may interact with TRPV1 and TRPA1 channels. Metformin promotes orofacial antinociception in both sexes in acute pain and is more effective in chronic pain in females than in males, through the modulation of TRPV1 and TRPA1 channels. These preclinical findings suggest a potential repositioning of metformin as an analgesic agent in acute and chronic orofacial pain states.

Indexed as

AnalgesicsFacial PainMetforminTRPA1 Cation ChannelTRPV Cation ChannelsAcroleinAnimalsCapsaicinChronic PainDisease Models, AnimalFemaleMaleMolecular Docking SimulationNociceptionRatsRats, WistarAcroleinAnalgesicsCapsaicincinnamaldehydeMetforminTransient Receptor Potential ChannelsTRPA1 Cation ChannelTrpa1 protein, ratTrpv1 protein, ratTRPV Cation ChannelsMetforminOrofacial nociceptionSex differencesTRP channels

Identifiers

PMID39356320

What Socratic holds

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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 Socratic graph.