Micronized Palmitoylethanolamide Reduces Joint Pain and Glial Cell Activation

Overview

Journal Inflamm Res

Specialties Allergy & Immunology
Pathology

Date 2018 Aug 20

PMID 30121836

Citations 11

Authors

Maria Lavinia Bartolucci

Ida Marini

Francesco Bortolotti

Daniela Impellizzeri

Rosanna Di Paola

Giuseppe Bruschetta

Rosalia Crupi

Marco Portelli

Angela Militi

Giacomo Oteri

Emanuela Esposito

Salvatore Cuzzocrea

Affiliations

Soon will be listed here.

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.

Citing Articles

Nutritional Strategies for Chronic Craniofacial Pain and Temporomandibular Disorders: Current Clinical and Preclinical Insights.

Piriyaprasath K, Kakihara Y, Hasegawa M, Iwamoto Y, Hasegawa Y, Fujii N Nutrients. 2024; 16(17).

PMID: 39275184 PMC: 11397166. DOI: 10.3390/nu16172868.

Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats.

Gaspar J, Healy C, Ferdousi M, Roche M, Finn D Biomedicines. 2021; 9(6).

PMID: 34072060 PMC: 8227714. DOI: 10.3390/biomedicines9060610.

Glia and Orofacial Pain: Progress and Future Directions.

Ye Y, Salvo E, Romero-Reyes M, Akerman S, Shimizu E, Kobayashi Y Int J Mol Sci. 2021; 22(10).

PMID: 34069553 PMC: 8160907. DOI: 10.3390/ijms22105345.

Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update.

Siracusa R, Di Paola R, Cuzzocrea S, Impellizzeri D Int J Mol Sci. 2021; 22(8).

PMID: 33918736 PMC: 8068842. DOI: 10.3390/ijms22083891.

Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide?.

Rocca G, Gamba D Animals (Basel). 2021; 11(4).

PMID: 33805489 PMC: 8065429. DOI: 10.3390/ani11040952.

References

Skaper S, Facci L, Giusti P . Glia and mast cells as targets for palmitoylethanolamide, an anti-inflammatory and neuroprotective lipid mediator. Mol Neurobiol. 2013; 48(2):340-52. DOI: 10.1007/s12035-013-8487-6. View

Fusco M, Skaper S, Coaccioli S, Varrassi G, Paladini A . Degenerative Joint Diseases and Neuroinflammation. Pain Pract. 2017; 17(4):522-532. DOI: 10.1111/papr.12551. View

Sessle B . Peripheral and central mechanisms of orofacial inflammatory pain. Int Rev Neurobiol. 2011; 97:179-206. DOI: 10.1016/B978-0-12-385198-7.00007-2. View

Guasti L, Richardson D, Jhaveri M, Eldeeb K, Barrett D, Elphick M . Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain. Mol Pain. 2009; 5:35. PMC: 2719614. DOI: 10.1186/1744-8069-5-35. View

Impellizzeri D, Bruschetta G, Cordaro M, Crupi R, Siracusa R, Esposito E . Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain. J Neuroinflammation. 2014; 11:136. PMC: 4171547. DOI: 10.1186/s12974-014-0136-0. View

Dworkin R, OConnor A, Audette J, Baron R, Gourlay G, Haanpaa M . Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010; 85(3 Suppl):S3-14. PMC: 2844007. DOI: 10.4065/mcp.2009.0649. View

Cairns B, Laursen J, Dong X, Gazerani P . Intraganglionic injection of a nitric oxide donator induces afferent mechanical sensitization that is attenuated by palmitoylethanolamide. Cephalalgia. 2014; 34(9):686-694. DOI: 10.1177/0333102414521510. View

Cerrato S, Brazis P, Della Valle M, Miolo A, Puigdemont A . Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFalpha release from canine skin mast cells. Vet Immunol Immunopathol. 2009; 133(1):9-15. DOI: 10.1016/j.vetimm.2009.06.011. View

Rahmati M, Mobasheri A, Mozafari M . Inflammatory mediators in osteoarthritis: A critical review of the state-of-the-art, current prospects, and future challenges. Bone. 2016; 85:81-90. DOI: 10.1016/j.bone.2016.01.019. View

10.

Muccioli G, Stella N . Microglia produce and hydrolyze palmitoylethanolamide. Neuropharmacology. 2007; 54(1):16-22. PMC: 2254322. DOI: 10.1016/j.neuropharm.2007.05.015. View

11.

Laursen J, Cairns B, Kumar U, Somvanshi R, Dong X, Arendt-Nielsen L . Nitric oxide release from trigeminal satellite glial cells is attenuated by glial modulators and glutamate. Int J Physiol Pathophysiol Pharmacol. 2014; 5(4):228-38. PMC: 3867700. View

12.

Villa G, Ceruti S, Zanardelli M, Magni G, Jasmin L, Ohara P . Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus. Mol Pain. 2010; 6:89. PMC: 3017032. DOI: 10.1186/1744-8069-6-89. View

13.

Marini I, Bartolucci M, Bortolotti F, Gatto M, Bonetti G . Palmitoylethanolamide versus a nonsteroidal anti-inflammatory drug in the treatment of temporomandibular joint inflammatory pain. J Orofac Pain. 2012; 26(2):99-104. View

14.

Wang X, Zhang J, Gan Y, Zhou Y . Current understanding of pathogenesis and treatment of TMJ osteoarthritis. J Dent Res. 2015; 94(5):666-73. DOI: 10.1177/0022034515574770. View

15.

Calabro R, Bramanti P . Occipital Neuralgia Responding to Palmitoylethanolamide. Headache. 2013; 57(10):E23-E24. DOI: 10.1111/head.12136. View

16.

Flake N, Bonebreak D, Gold M . Estrogen and inflammation increase the excitability of rat temporomandibular joint afferent neurons. J Neurophysiol. 2004; 93(3):1585-97. PMC: 2838234. DOI: 10.1152/jn.00269.2004. View

17.

Raghavendra V, Tanga F, DeLeo J . Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci. 2004; 20(2):467-73. DOI: 10.1111/j.1460-9568.2004.03514.x. View

18.

Wang S, Song L, Tan Y, Ma Y, Tian Y, Jin X . A functional relationship between trigeminal astroglial activation and NR1 expression in a rat model of temporomandibular joint inflammation. Pain Med. 2012; 13(12):1590-600. PMC: 3527674. DOI: 10.1111/j.1526-4637.2012.01511.x. View

19.

Luongo L, Guida F, Boccella S, Bellini G, Gatta L, Rossi F . Palmitoylethanolamide reduces formalin-induced neuropathic-like behaviour through spinal glial/microglial phenotypical changes in mice. CNS Neurol Disord Drug Targets. 2013; 12(1):45-54. DOI: 10.2174/1871527311312010009. View

20.

Bisogno T, Maurelli S, Melck D, De Petrocellis L, Di Marzo V . Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes. J Biol Chem. 1997; 272(6):3315-23. DOI: 10.1074/jbc.272.6.3315. View