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Micronized palmitoylethanolamide reduces joint pain and glial cell activation

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Abstract

Objective and design

Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.

Materials and subject

TMJ was induced in rats with the injection of complete Freund’s adjuvant (CFA) emulsion into the left TMJ capsule.

Treatment

The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.

Methods

Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.

Results

CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.

Conclusions

The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.

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Acknowledgements

The authors would like to thank Mrs Maria Antonietta Medici for her excellent technical assistance during this study, Mr Francesco Soraci for his secretarial and administrative assistance and Miss Valentina Malvagni for her editorial assistance with the manuscript.

Funding

The authors state that no funding sources were provided.

Author information

Authors and Affiliations

  1. Section of Orthodontics, Department of Biomedical Sciences, University of Bologna, Via San Vitale 59, 40125, Bologna, Italy

    Maria Lavinia Bartolucci, Ida Marini & Francesco Bortolotti

  2. Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166, Messina, Italy

    Daniela Impellizzeri, Rosanna Di Paola, Giuseppe Bruschetta, Rosalia Crupi, Emanuela Esposito & Salvatore Cuzzocrea

  3. Department of Biomedical, Dental Science and Morphological and Functional Images, Dental School, 98125, Messina, Italy

    Marco Portelli, Angela Militi & Giacomo Oteri

  4. Department of Pharmacological and Physiological Sciences, Saint Louis University, School of Medicine, 1402 South Grand Blvd, St. Louis, MO, 63104, USA

    Salvatore Cuzzocrea

Authors
  1. Maria Lavinia Bartolucci
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  2. Ida Marini
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  3. Francesco Bortolotti
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  7. Rosalia Crupi
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  8. Marco Portelli
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  9. Angela Militi
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  11. Emanuela Esposito
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  12. Salvatore Cuzzocrea
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Corresponding author

Correspondence to Salvatore Cuzzocrea.

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Conflict of interest

Salvatore Cuzzocrea is co-inventor on a patent with Epitech (Application number: 20150057269), along with academic investigators from a different institution. The subject matter of said patent (which deals with compositions and methods for the modulation of specific amidases for N-acylethanolamines for use in the therapy of inflammatory diseases) bears no relation to the present manuscript. The authors declare no potential conflict of interest with respect to the authorship and/or publication of this article.

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Responsible Editor: John Di Battista.

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Bartolucci, M.L., Marini, I., Bortolotti, F. et al. Micronized palmitoylethanolamide reduces joint pain and glial cell activation. Inflamm. Res. 67, 891–901 (2018). https://doi.org/10.1007/s00011-018-1179-y

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  • DOI: https://doi.org/10.1007/s00011-018-1179-y

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