Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway
Fibromyalgia is a chronic condition characterized by persistent widespread pain that significantly reduces quality of life in patients. The purinergic P2X7 receptor (P2X7R) seems to be involved in different pain states and neuroinflammation. The purpose of this study is to investigate the positive e...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/12/6471 |
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| author | Ramona D’Amico Roberta Fusco Rosalba Siracusa Daniela Impellizzeri Alessio Filippo Peritore Enrico Gugliandolo Livia Interdonato Andrea Maria Sforza Rosalia Crupi Salvatore Cuzzocrea Tiziana Genovese Marika Cordaro Rosanna Di Paola |
| author_facet | Ramona D’Amico Roberta Fusco Rosalba Siracusa Daniela Impellizzeri Alessio Filippo Peritore Enrico Gugliandolo Livia Interdonato Andrea Maria Sforza Rosalia Crupi Salvatore Cuzzocrea Tiziana Genovese Marika Cordaro Rosanna Di Paola |
| author_sort | Ramona D’Amico |
| collection | DOAJ |
| description | Fibromyalgia is a chronic condition characterized by persistent widespread pain that significantly reduces quality of life in patients. The purinergic P2X7 receptor (P2X7R) seems to be involved in different pain states and neuroinflammation. The purpose of this study is to investigate the positive effects of P2X7R inhibition by the antagonist Brilliant Blue G (BBG) in a rat model of reserpine-induced fibromyalgia. Sprague–Dawley male rats were injected with 1 mg/kg of reserpine for three consecutive days. Later, animals were administered BBG (50 mg/kg) intraperitoneally for seven days. Reserpine injections induced a significant increase in pain pro-inflammatory mediators as well as a significant increase in neuroinflammation. Chronic pain, in turn, led to depressive-like symptoms and reduced neurogenesis. Blockage of P2X7R by BBG administrations is able to attenuate the behavioral deficits, pain mediators and microglial activation induced by reserpine injection. Additionally, BBG prevents NLRP3 inflammasome activation and consequently the release of active interleukin (IL)-1 and IL-18, involved in the activation of nociceptors. In conclusion, these results suggest that inhibition of P2X7R should be further investigated to develop a potential approach for the management of fibromyalgia. |
| first_indexed | 2024-03-10T10:20:43Z |
| format | Article |
| id | doaj.art-ac5bc81a8c18480e889da3b40369e359 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:20:43Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ac5bc81a8c18480e889da3b40369e3592023-11-22T00:26:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012212647110.3390/ijms22126471Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 PathwayRamona D’Amico0Roberta Fusco1Rosalba Siracusa2Daniela Impellizzeri3Alessio Filippo Peritore4Enrico Gugliandolo5Livia Interdonato6Andrea Maria Sforza7Rosalia Crupi8Salvatore Cuzzocrea9Tiziana Genovese10Marika Cordaro11Rosanna Di Paola12Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Veterinary Sciences, University of Messina, 98168 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Veterinary Sciences, University of Messina, 98168 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyDepartment of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, via Consolare Valeria, 98125 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyFibromyalgia is a chronic condition characterized by persistent widespread pain that significantly reduces quality of life in patients. The purinergic P2X7 receptor (P2X7R) seems to be involved in different pain states and neuroinflammation. The purpose of this study is to investigate the positive effects of P2X7R inhibition by the antagonist Brilliant Blue G (BBG) in a rat model of reserpine-induced fibromyalgia. Sprague–Dawley male rats were injected with 1 mg/kg of reserpine for three consecutive days. Later, animals were administered BBG (50 mg/kg) intraperitoneally for seven days. Reserpine injections induced a significant increase in pain pro-inflammatory mediators as well as a significant increase in neuroinflammation. Chronic pain, in turn, led to depressive-like symptoms and reduced neurogenesis. Blockage of P2X7R by BBG administrations is able to attenuate the behavioral deficits, pain mediators and microglial activation induced by reserpine injection. Additionally, BBG prevents NLRP3 inflammasome activation and consequently the release of active interleukin (IL)-1 and IL-18, involved in the activation of nociceptors. In conclusion, these results suggest that inhibition of P2X7R should be further investigated to develop a potential approach for the management of fibromyalgia.https://www.mdpi.com/1422-0067/22/12/6471fibromyalgiaP2X7 receptorNLRP3 inflammasomeneuroinflammation |
| spellingShingle | Ramona D’Amico Roberta Fusco Rosalba Siracusa Daniela Impellizzeri Alessio Filippo Peritore Enrico Gugliandolo Livia Interdonato Andrea Maria Sforza Rosalia Crupi Salvatore Cuzzocrea Tiziana Genovese Marika Cordaro Rosanna Di Paola Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway International Journal of Molecular Sciences fibromyalgia P2X7 receptor NLRP3 inflammasome neuroinflammation |
| title | Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway |
| title_full | Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway |
| title_fullStr | Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway |
| title_full_unstemmed | Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway |
| title_short | Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway |
| title_sort | inhibition of p2x7 purinergic receptor ameliorates fibromyalgia syndrome by suppressing nlrp3 pathway |
| topic | fibromyalgia P2X7 receptor NLRP3 inflammasome neuroinflammation |
| url | https://www.mdpi.com/1422-0067/22/12/6471 |
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