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Biomolecules
Volume 12
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10.3390/biom12081155
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Article

The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice

by
Claudia Cristiano
,
Carmen Avagliano
,
Mariarosaria Cuozzo
,
Fabrizio Maria Liguori
,
Antonio Calignano
and
Roberto Russo
*
Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy
*
Author to whom correspondence should be addressed.
Biomolecules 2022, 12(8), 1155; https://doi.org/10.3390/biom12081155
Submission received: 29 July 2022 / Revised: 17 August 2022 / Accepted: 18 August 2022 / Published: 20 August 2022
(This article belongs to the Special Issue To Go Where Nature Leads: Focus on Palmitoylethanolamide and Related ALIAmides As Innovative Approach to Neuroinflammatory and Pain-Related Disease States in Honor of Doctor Francesco Della Valle)
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Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of antineoplastic drugs, particularly paclitaxel (PTX). It can affect the quality of patients’ lives and increase the risk of developing mood disorders. Although several drugs are recommended, they yielded inconclusive results in clinical trials. The aim of the present work is to investigate whether the palmitoylethanolamide (PEA) would reduce PTX-induced CIPN and associated mood disorders. Moreover, the role PPAR-α and the endocannabinoid system will also be investigated. CIPN was induced by intraperitoneally injection of PTX (8 mg/kg) every other day for a week. PEA, 30 mg/kg, was orally administrated in a bioavailable form (i.e., ultramicronized PEA, um-PEA) one hour after the last PTX injection, for 7 days. In the antagonism experiments, AM281 (1 mg/kg) and GW6471 (2 mg/kg) were administrated 30 min before um-PEA. Our results demonstrated that um-PEA reduced the development of hypersensitivity with the effect being associated with the reduction in spinal and hippocampal pro-inflammatory cytokines, as well as antidepressive and anxiolytic effects. Moreover, the PPAR-α and CB1 receptor antagonists blocked the behavioral and antinociceptive effects of um-PEA. Our findings suggest that um-PEA is a promising adjunct in CIPN and associated mood disorders through the activation of PPAR-α, which influences the endocannabinoid system.
Keywords: paclitaxel; um-PEA; inflammation; neuropathic pain; behavior; cannabinoids; PPAR-α paclitaxel; um-PEA; inflammation; neuropathic pain; behavior; cannabinoids; PPAR-α
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MDPI and ACS Style

Cristiano, C.; Avagliano, C.; Cuozzo, M.; Liguori, F.M.; Calignano, A.; Russo, R. The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice. Biomolecules 2022, 12, 1155. https://doi.org/10.3390/biom12081155

AMA Style

Cristiano C, Avagliano C, Cuozzo M, Liguori FM, Calignano A, Russo R. The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice. Biomolecules. 2022; 12(8):1155. https://doi.org/10.3390/biom12081155

Chicago/Turabian Style

Cristiano, Claudia, Carmen Avagliano, Mariarosaria Cuozzo, Fabrizio Maria Liguori, Antonio Calignano, and Roberto Russo. 2022. "The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice" Biomolecules 12, no. 8: 1155. https://doi.org/10.3390/biom12081155

APA Style

Cristiano, C., Avagliano, C., Cuozzo, M., Liguori, F. M., Calignano, A., & Russo, R. (2022). The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice. Biomolecules, 12(8), 1155. https://doi.org/10.3390/biom12081155

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