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Analysis of the Influence of IL-6 and the Activation of the Jak/Stat3 Pathway in Fibromyalgia

Background: Fibromyalgia is a medical condition that affects a small percentage of the population, with no known effective treatment. There is evidence to suggest that inflammation is a key factor in the nerve sensitization that characterizes the disorder. Therefore, this paper concentrates on the r...

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Autores principales: Marino, Ylenia, Arangia, Alessia, Cordaro, Marika, Siracusa, Rosalba, D’Amico, Ramona, Impellizzeri, Daniela, Cupi, Rosalia, Peritore, Alessio Filippo, Gugliandolo, Enrico, Fusco, Roberta, Cuzzocrea, Salvatore, Di Paola, Rosanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045851/
https://www.ncbi.nlm.nih.gov/pubmed/36979771
http://dx.doi.org/10.3390/biomedicines11030792
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author Marino, Ylenia
Arangia, Alessia
Cordaro, Marika
Siracusa, Rosalba
D’Amico, Ramona
Impellizzeri, Daniela
Cupi, Rosalia
Peritore, Alessio Filippo
Gugliandolo, Enrico
Fusco, Roberta
Cuzzocrea, Salvatore
Di Paola, Rosanna
author_facet Marino, Ylenia
Arangia, Alessia
Cordaro, Marika
Siracusa, Rosalba
D’Amico, Ramona
Impellizzeri, Daniela
Cupi, Rosalia
Peritore, Alessio Filippo
Gugliandolo, Enrico
Fusco, Roberta
Cuzzocrea, Salvatore
Di Paola, Rosanna
author_sort Marino, Ylenia
collection PubMed
description Background: Fibromyalgia is a medical condition that affects a small percentage of the population, with no known effective treatment. There is evidence to suggest that inflammation is a key factor in the nerve sensitization that characterizes the disorder. Therefore, this paper concentrates on the role of IL-6 in fibromyalgia and the related pain-like symptoms. Methods: This work aimed to evaluate Sprague–Dawley rats, which were injected for three consecutive days with 1 mg/kg of reserpine; IL-6-R Ab was intraperitoneally injected at 1.5 mg/kg seven days after the first reserpine injection. Behavioral analyses were conducted at the beginning of the experiment and at seven and twenty-one days from the first reserpine injection. At this timepoint, the animals were sacrificed, and tissues were collected for molecular and histological analysis. Results: Our data showed the analgesic effect of IL-6-R-Ab administration on mechanical allodynia and thermal hyperalgesia. Additionally, the reserpine + IL-6-R-Ab group showed a reduced expression of the pain-related mediators cFOS and NFG and reduced levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and chemokines (Cxcl5, Cxcl10 and Cx3cl1). From the molecular point of view, the IL-6-R-Ab administration reduced the gp130 phosphorylation and the activation of the Jak/STAT3 pathway. Additionally, the IL-6-R Ab reduced the activation of neuroinflammatory cells. Conclusions: Our study showed that IL-6 plays a crucial role in fibromyalgia by triggering the Jak/STAT3 pathway, leading to an increase in chemokine levels and activating glial cells.
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spelling pubmed-100458512023-03-29 Analysis of the Influence of IL-6 and the Activation of the Jak/Stat3 Pathway in Fibromyalgia Marino, Ylenia Arangia, Alessia Cordaro, Marika Siracusa, Rosalba D’Amico, Ramona Impellizzeri, Daniela Cupi, Rosalia Peritore, Alessio Filippo Gugliandolo, Enrico Fusco, Roberta Cuzzocrea, Salvatore Di Paola, Rosanna Biomedicines Article Background: Fibromyalgia is a medical condition that affects a small percentage of the population, with no known effective treatment. There is evidence to suggest that inflammation is a key factor in the nerve sensitization that characterizes the disorder. Therefore, this paper concentrates on the role of IL-6 in fibromyalgia and the related pain-like symptoms. Methods: This work aimed to evaluate Sprague–Dawley rats, which were injected for three consecutive days with 1 mg/kg of reserpine; IL-6-R Ab was intraperitoneally injected at 1.5 mg/kg seven days after the first reserpine injection. Behavioral analyses were conducted at the beginning of the experiment and at seven and twenty-one days from the first reserpine injection. At this timepoint, the animals were sacrificed, and tissues were collected for molecular and histological analysis. Results: Our data showed the analgesic effect of IL-6-R-Ab administration on mechanical allodynia and thermal hyperalgesia. Additionally, the reserpine + IL-6-R-Ab group showed a reduced expression of the pain-related mediators cFOS and NFG and reduced levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and chemokines (Cxcl5, Cxcl10 and Cx3cl1). From the molecular point of view, the IL-6-R-Ab administration reduced the gp130 phosphorylation and the activation of the Jak/STAT3 pathway. Additionally, the IL-6-R Ab reduced the activation of neuroinflammatory cells. Conclusions: Our study showed that IL-6 plays a crucial role in fibromyalgia by triggering the Jak/STAT3 pathway, leading to an increase in chemokine levels and activating glial cells. MDPI 2023-03-06 /pmc/articles/PMC10045851/ /pubmed/36979771 http://dx.doi.org/10.3390/biomedicines11030792 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Marino, Ylenia
Arangia, Alessia
Cordaro, Marika
Siracusa, Rosalba
D’Amico, Ramona
Impellizzeri, Daniela
Cupi, Rosalia
Peritore, Alessio Filippo
Gugliandolo, Enrico
Fusco, Roberta
Cuzzocrea, Salvatore
Di Paola, Rosanna
Analysis of the Influence of IL-6 and the Activation of the Jak/Stat3 Pathway in Fibromyalgia
title Analysis of the Influence of IL-6 and the Activation of the Jak/Stat3 Pathway in Fibromyalgia
title_full Analysis of the Influence of IL-6 and the Activation of the Jak/Stat3 Pathway in Fibromyalgia
title_fullStr Analysis of the Influence of IL-6 and the Activation of the Jak/Stat3 Pathway in Fibromyalgia
title_full_unstemmed Analysis of the Influence of IL-6 and the Activation of the Jak/Stat3 Pathway in Fibromyalgia
title_short Analysis of the Influence of IL-6 and the Activation of the Jak/Stat3 Pathway in Fibromyalgia
title_sort analysis of the influence of il-6 and the activation of the jak/stat3 pathway in fibromyalgia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045851/
https://www.ncbi.nlm.nih.gov/pubmed/36979771
http://dx.doi.org/10.3390/biomedicines11030792
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