Evidence map›Paper›PMID 39495266›Full record

ArticleNaunyn-Schmiedeberg's archives of pharmacology2025

Enhancing orofacial pain relief: α-phellandrene complexed with hydroxypropyl-β-cyclodextrin mitigates orofacial nociception in rodents.

Brennda Gonzaga Machado, Fabíolla Rocha Santos Passos, Ângelo Roberto Antoniolli, Erik W Menezes Pereira, Tiffany Karoline Barroso Santos, Brenda Souza Monteiro, Pollyana de Souza Siqueira Lima, Saulo Santos Matos, Marcelo Cavalcante Duarte, Adriano Antunes de Souza Araújo and 5 more

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In one paragraph

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 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

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

1 citing paper in PubMed.

  1. 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

15 authors.

Brennda Gonzaga MachadoDepartment of Physiology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
Fabíolla Rocha Santos PassosDepartment of Physiology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
Ângelo Roberto AntoniolliDepartment of Physiology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
Erik W Menezes PereiraDepartment of Physiology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
Tiffany Karoline Barroso SantosDepartment of Physiology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
Brenda Souza MonteiroDepartment of Physiology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
Pollyana de Souza Siqueira LimaDepartment of Odontology, Centro Universitário de Excelência (Unex), Feira de Santana, BA, Brazil.
Saulo Santos MatosDepartment of Pharmacy, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
Marcelo Cavalcante DuarteDepartment of Pharmacy, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
Adriano Antunes de Souza AraújoDepartment of Pharmacy, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
Jackson Roberto Guedes da Silva AlmeidaNúcleo de Estudos E Pesquisas de Plantas Medicinais (Neplame), Federal University of San Francisco Valley, Petrolina, PE, Brazil.
Raimundo Gonçalves Oliveira JúniorFaculty of Pharmacy, University Paris Cité (UPCité), Paris, France.
Henrique Douglas Melo CoutinhoDepartment of Biological Chemistry, Regional University of Cariri (URCA), Crato, CE, Brazil. hdmcoutinho@gmail.com.
Lucindo J Quintans-JúniorDepartment of Physiology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil.
Jullyana de Souza Siqueira QuintansDepartment of Physiology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil. jullyanaquintans@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Orofacial pain affects 10-15% of adults and can severely impact quality of life. Despite ongoing treatment challenges, monoterpene alpha-phellandrene (PHE) shows potential therapeutic benefits. This study aimed to develop and evaluate an inclusion complex of PHE with hydroxypropyl-beta-cyclodextrin (PHE-HPβCD) for treating orofacial pain. The PHE-HPβCD complex was created using physical mixing and characterized by differential scanning calorimetry (DSC) and high-performance liquid chromatography (HPLC) to determine encapsulation efficiency. The complex exhibited a 70.45% encapsulation efficiency. Male Swiss mice were used in models of orofacial pain induced by formalin, cinnamaldehyde, glutamate, and corneal nociception by hypertonic saline. Additionally, cytokine levels (TNF-α and IL-1β) were measured in the upper lip tissue of mice subjected to the formalin model. Both PHE and PHE-HPβCD showed significant antinociceptive effects at a 50 mg/kg dose during formalin-induced pain, reducing both neurogenic and inflammatory phases of pain. PHE-HPβCD also reduced TNF-α and IL-1β levels. For cinnamaldehyde and glutamate-induced nociception, both treatments reduced pain behavior, but only PHE-HPβCD decreased eye wipes in corneal nociception. These results suggest that PHE, especially in complexed form, alleviates orofacial pain by potentially modulating pain-related receptors (TRPA1 and TRPV1), mediators, like glutamate, and reducing pro-inflammatory cytokines. Further research is needed to explore the precise mechanisms of PHE in chronic orofacial pain models, but the study indicates promising avenues for new pain treatments.

Indexed as

2-Hydroxypropyl-beta-cyclodextrinAnalgesicsCyclohexane MonoterpenesFacial PainNociceptionAcroleinAnimalsDisease Models, AnimalFormaldehydeInterleukin-1betaMaleMiceTumor Necrosis Factor-alpha2-Hydroxypropyl-beta-cyclodextrinAcroleinAnalgesicscinnamaldehydeCyclohexane MonoterpenesFormaldehydeInterleukin-1betaTumor Necrosis Factor-alphaCyclodextrinMonoterpenesOrofacial painα-phellandrene

Identifiers

PMID39495266

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.