{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:28:41Z","timestamp":1792132121341,"version":"4.4.0"},"reference-count":79,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013Dawley 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.<\/jats:p>","DOI":"10.3390\/ijms22126471","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T21:58:32Z","timestamp":1623880712000},"page":"6471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-3871","authenticated-orcid":false,"given":"Ramona","family":"D\u2019Amico","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0223-1403","authenticated-orcid":false,"given":"Roberta","family":"Fusco","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7868-2505","authenticated-orcid":false,"given":"Rosalba","family":"Siracusa","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9492-3161","authenticated-orcid":false,"given":"Daniela","family":"Impellizzeri","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-990X","authenticated-orcid":false,"given":"Alessio Filippo","family":"Peritore","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6840-3154","authenticated-orcid":false,"given":"Enrico","family":"Gugliandolo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Interdonato","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Maria","family":"Sforza","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-3132","authenticated-orcid":false,"given":"Rosalia","family":"Crupi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-3690","authenticated-orcid":false,"given":"Salvatore","family":"Cuzzocrea","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Genovese","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-0043","authenticated-orcid":false,"given":"Marika","family":"Cordaro","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6725-8581","authenticated-orcid":false,"given":"Rosanna","family":"Di Paola","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Favero, G., Trapletti, V., Bonomini, F., Stacchiotti, A., Lavazza, A., Rodella, L.F., and Rezzani, R. (2017). Oral Supplementation of Melatonin Protects against Fibromyalgia-Related Skeletal Muscle Alterations in Reserpine-Induced Myalgia Rats. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071389"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ejphar.2018.03.011","article-title":"Effects of pregabalin and duloxetine on neurotransmitters in the dorsal horn of the spinal cord in a rat model of fibromyalgia","volume":"827","author":"Kiso","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bbi.2020.07.015","article-title":"Chronic stress followed by social isolation promotes depressive-like behaviour, alters microglial and astrocyte biology and reduces hippocampal neurogenesis in male mice","volume":"91","author":"Onorato","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nrn3855","article-title":"Molecular mechanisms in the regulation of adult neurogenesis during stress","volume":"16","author":"Egeland","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1097\/j.pain.0000000000000332","article-title":"Role of adult hippocampal neurogenesis in persistent pain","volume":"157","author":"Apkarian","year":"2016","journal-title":"Pain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5747","DOI":"10.1523\/JNEUROSCI.0587-12.2012","article-title":"Abnormalities in Hippocampal Functioning with Persistent Pain","volume":"32","author":"Mutso","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.bbr.2011.09.023","article-title":"Different pathophysiology underlying animal models of fibromyalgia and neuropathic pain: Comparison of reserpine-induced myalgia and chronic constriction injury rats","volume":"226","author":"Nagakura","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_8","first-page":"1343","article-title":"Attenuation of reserpine-induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol","volume":"19","author":"Yao","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_9","first-page":"289","article-title":"Brain plasticity and microglia: Is transsynaptic glial activation in the thalamus after limb denervation linked to cortical plasticity and central sensitisation?","volume":"96","author":"Banati","year":"2002","journal-title":"J. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.3389\/fphys.2020.01016","article-title":"The NLRP3 Inflammasome: Role and Therapeutic Potential in Pain Treatment","volume":"11","author":"Starobova","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1007\/s00702-015-1445-x","article-title":"Diverse effects of Brilliant Blue G administration in models of trigeminal activation in the rat","volume":"122","author":"Tar","year":"2015","journal-title":"J. Neural Transm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6359","DOI":"10.12659\/MSM.915865","article-title":"Brilliant Blue G Inhibits Inflammasome Activation and Reduces Disruption of Blood\u2013Spinal Cord Barrier Induced by Spinal Cord Injury in Rats","volume":"25","author":"Zhou","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1113\/jphysiol.2007.143933","article-title":"Release of ATP in the central nervous system during systemic inflammation: Real-time measurement in the hypothalamus of conscious rabbits","volume":"585","author":"Gourine","year":"2007","journal-title":"J. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.3892\/mmr.2015.3607","article-title":"Neuroprotective effects of brilliant blue G on the brain following traumatic brain injury in rats","volume":"12","author":"Wang","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.3389\/fphar.2020.01148","article-title":"Duality of P2X7 Receptor in Amyotrophic Lateral Sclerosis","volume":"11","author":"Amadio","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1111\/j.1476-5381.2009.00596.x","article-title":"A comparative analysis of the activity of ligands acting at P2X and P2Y receptor subtypes in models of neuropathic, acute and inflammatory pain","volume":"159","author":"Gyires","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1096\/fj.09-138883","article-title":"The P2X 7 purinergic receptor: From physiology to neurological disorders","volume":"24","author":"Skaper","year":"2009","journal-title":"FASEB J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yoshida, S., Hagiwara, Y., Tsuchiya, M., Shinoda, M., Koide, M., Hatakeyama, H., Chaweewannakorn, C., Suzuki, K., Yano, T., and Sogi, Y. (2019). Involvement of inflammasome activation via elevation of uric acid level in nociception in a mouse model of muscle pain. Mol. Pain.","DOI":"10.1177\/1744806919858797"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yoshida, S., Hagiwara, Y., Tsuchiya, M., Shinoda, M., Koide, M., Hatakeyama, H., Chaweewannakorn, C., Yano, T., Sogi, Y., and Itaya, N. (2018). Involvement of neutrophils and interleukin-18 in nociception in a mouse model of muscle pain. Mol. Pain, 14.","DOI":"10.1177\/1744806918757286"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jpain.2017.10.003","article-title":"IL-18 Contributes to Bone Cancer Pain by Regulating Glia Cells and Neuron Interaction","volume":"19","author":"Liu","year":"2018","journal-title":"J. Pain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/bja\/aew376","article-title":"The inflammasome as a target for pain therapy","volume":"117","author":"Zhang","year":"2016","journal-title":"Br. J. Anaesth."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1124\/mol.58.1.82","article-title":"Brilliant Blue G Selectively Blocks ATP-Gated Rat P2X7Receptors","volume":"58","author":"Jiang","year":"2000","journal-title":"Mol. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1021\/acschemneuro.1c00095","article-title":"Depression Induced by Chronic Unpredictable Mild Stress Increases Susceptibility to Parkinson\u2019s Disease in Mice via Neuroinflammation Mediated by P2X7 Receptor","volume":"12","author":"Ren","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"R223","DOI":"10.1152\/ajpregu.00093.2020","article-title":"Intrathecal injection of brilliant blue G, a P2X7 antagonist, attenuates the exercise pressor reflex in rats","volume":"319","author":"Estrada","year":"2020","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12489","DOI":"10.1073\/pnas.0902531106","article-title":"Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury","volume":"106","author":"Peng","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3389\/fncel.2019.00353","article-title":"Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome","volume":"13","author":"Theoharides","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/ijcp.12757","article-title":"Fibromyalgia: Management strategies for primary care providers","volume":"70","author":"Arnold","year":"2016","journal-title":"Int. J. Clin. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Favero, G., Bonomini, F., Franco, C., and Rezzani, R. (2019). Mitochondrial Dysfunction in Skeletal Muscle of a Fibromyalgia Model: The Potential Benefits of Melatonin. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030765"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1002\/med.21710","article-title":"The purinergic P2X7 receptor as a potential drug target to combat neuroinflammation in neurodegenerative diseases","volume":"40","author":"Calzaferri","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1021\/acs.jmedchem.0c02145","article-title":"Synthesis and Pharmacological Evaluation of Novel Non-nucleotide Purine Derivatives as P2X7 Antagonists for the Treatment of Neuroinflammation","volume":"64","author":"Calzaferri","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.brainresbull.2017.09.006","article-title":"The P2X 7 receptor in dorsal root ganglia is involved in HIV gp120-associated neuropathic pain","volume":"135","author":"Wu","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1124\/mol.118.115022","article-title":"A Mechanism-Based Approach to P2X7 Receptor Action","volume":"95","author":"Ugur","year":"2019","journal-title":"Mol. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.4049\/jimmunol.176.7.3877","article-title":"The P2X7Receptor: A Key Player in IL-1 Processing and Release","volume":"176","author":"Ferrari","year":"2006","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.bcp.2017.12.021","article-title":"The P2X7 receptor: A main player in inflammation","volume":"151","author":"Adinolfi","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.coph.2019.02.012","article-title":"Role of the P2X7 receptor in tumor-associated inflammation","volume":"47","author":"Adinolfi","year":"2019","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.neuroscience.2011.06.083","article-title":"Central sensitization of nociceptive neurons in rat medullary dorsal horn involves purinergic P2X7 receptors","volume":"192","author":"Itoh","year":"2011","journal-title":"Neuroscience"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1213\/ANE.0000000000001097","article-title":"Electroacupuncture Relieves Nerve Injury\u2013Induced Pain Hypersensitivity via the Inhibition of Spinal P2X7 Receptor\u2013Positive Microglia","volume":"122","author":"Chen","year":"2016","journal-title":"Anesthesia Analg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.pain.2005.01.002","article-title":"Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain","volume":"114","author":"Chessell","year":"2005","journal-title":"Pain"},{"key":"ref_39","first-page":"13191","article-title":"Impact of mast cells in fibromyalgia and low-grade chronic inflammation: Can IL-37 play a role?","volume":"33","author":"Conti","year":"2019","journal-title":"Dermatol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29069","DOI":"10.3390\/ijms161226151","article-title":"Mast Cell-Mediated Mechanisms of Nociception","volume":"16","author":"Aich","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fusco, R., Siracusa, R., D\u2019Amico, R., Peritore, A.F., Cordaro, M., Gugliandolo, E., Crupi, R., Impellizzeri, D., Cuzzocrea, S., and Di Paola, R. (2019). Melatonin Plus Folic Acid Treatment Ameliorates Reserpine-Induced Fibromyalgia: An Evaluation of Pain, Oxidative Stress, and Inflammation. Antioxidants, 8.","DOI":"10.3390\/antiox8120628"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/imr.12634","article-title":"Mast cells as sources of cytokines, chemokines, and growth factors","volume":"282","author":"Mukai","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Peritore, A.F., Siracusa, R., Fusco, R., Gugliandolo, E., D\u2019Amico, R., Cordaro, M., Crupi, R., Genovese, T., Impellizzeri, D., and Cuzzocrea, S. (2020). Ultramicronized Palmitoylethanolamide and Paracetamol, a New Association to Relieve Hyperalgesia and Pain in a Sciatic Nerve Injury Model in Rat. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103509"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e925491-1","DOI":"10.12659\/MSM.925491","article-title":"P2X7 Receptor (P2X7R) of Microglia Mediates Neuroinflammation by Regulating (NOD)-Like Receptor Protein 3 (NLRP3) Inflammasome-Dependent Inflammation After Spinal Cord Injury","volume":"26","author":"Fan","year":"2020","journal-title":"Med Sci. Monit."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1159\/000449183","article-title":"Implication of Hypothalamus in Alleviating Spinal Cord Injury-Induced Neuropathic Pain","volume":"23","author":"Crowell","year":"2016","journal-title":"Ann. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.neuro.051508.135531","article-title":"Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage","volume":"32","author":"Costigan","year":"2009","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1096\/fj.14-268714","article-title":"The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein","volume":"29","author":"Franceschini","year":"2015","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Fusco, R., Siracusa, R., Genovese, T., Cuzzocrea, S., and Di Paola, R. (2020). Focus on the Role of NLRP3 Inflammasome in Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124223"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/SHK.0000000000001137","article-title":"Involvement of TLR4 and PPAR-\u03b1 Receptors in Host Response and NLRP3 Inflammasome Activation, Against Pulmonary Infection With Pseudomonas Aeruginosa","volume":"51","author":"Gugliandolo","year":"2019","journal-title":"Shock"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"D\u2019Amico, R., Fusco, R., Cordaro, M., Siracusa, R., Peritore, A.F., Gugliandolo, E., Crupi, R., Scuto, M., Cuzzocrea, S., and Di Paola, R. (2020). Modulation of NLRP3 Inflammasome through Formyl Peptide Receptor 1 (Fpr-1) Pathway as a New Therapeutic Target in Bronchiolitis Obliterans Syndrome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062144"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"14062","DOI":"10.1523\/JNEUROSCI.3795-08.2008","article-title":"Nociceptors Are Interleukin-1 Sensors","volume":"28","author":"Binshtok","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_52","first-page":"1","article-title":"NLRP3 Inflammasome Expression and Signaling in Human Diabetic Wounds and in High Glucose Induced Macrophages","volume":"2017","author":"Zhang","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.physbeh.2015.07.033","article-title":"Depressive-like symptoms in a reserpine-induced model of fibromyalgia in rats","volume":"151","year":"2015","journal-title":"Physiol. Behav."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.bbi.2014.04.003","article-title":"Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis and plasticity are dependent on TNFR1 signaling","volume":"41","author":"Dellarole","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2147\/JPR.S71959","article-title":"Fibromyalgia patients have reduced hippocampal volume compared with healthy controls","volume":"8","author":"McCrae","year":"2015","journal-title":"J. Pain Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"12304","DOI":"10.1523\/JNEUROSCI.0312-14.2014","article-title":"Anxiety- and Depression-Like Behavior and Impaired Neurogenesis Evoked by Peripheral Neuropathy Persist following Resolution of Prolonged Tactile Hypersensitivity","volume":"34","author":"Dimitrov","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"768","DOI":"10.3892\/mmr.2016.6070","article-title":"Inhibiting purinergic P2X7 receptors with the antagonist brilliant blue G is neuroprotective in an intranigral lipopolysaccharide animal model of Parkinson\u2019s disease","volume":"15","author":"Wang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Fusco, R., Gugliandolo, E., Siracusa, R., Scuto, M., Cordaro, M., D\u2019Amico, R., Evangelista, M., Peli, A., Peritore, A.F., and Impellizzeri, D. (2020). Formyl Peptide Receptor 1 Signaling in Acute Inflammation and Neural Differentiation Induced by Traumatic Brain Injury. Biology, 9.","DOI":"10.3390\/biology9090238"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"D\u2019Amico, R., Siracusa, R., Fusco, R., Cordaro, M., Genovese, T., Peritore, A.F., Gugliandolo, E., Crupi, R., Impellizzeri, D., and Cuzzocrea, S. (2020). Protective effects of Colomast\u00ae, A New Formulation of Adelmidrol and Sodium Hyaluronate, in A Mouse Model of Acute Restraint Stress. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218136"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11364","DOI":"10.1096\/fj.201900538R","article-title":"The neuroprotective effects of micronized PEA (PEA-m) formulation on diabetic peripheral neuropathy in mice","volume":"33","author":"Impellizzeri","year":"2019","journal-title":"FASEB J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fphar.2018.00051","article-title":"The Antioxidant Activity of Pistachios Reduces Cardiac Tissue Injury of Acute Ischemia\/Reperfusion (I\/R) in Diabetic Streptozotocin (STZ)-Induced Hyperglycaemic Rats","volume":"9","author":"Fusco","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/SHK.0000000000000578","article-title":"Protective Effects of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Injury in VIVO","volume":"46","author":"Cordaro","year":"2016","journal-title":"Shock"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Fusco, R., Cordaro, M., Siracusa, R., D\u2019Amico, R., Genovese, T., Gugliandolo, E., Peritore, A.F., Crupi, R., Impellizzeri, D., and Cuzzocrea, S. (2020). Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury. Antioxidants, 9.","DOI":"10.3390\/antiox9090781"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Siracusa, R., Fusco, R., Cordaro, M., Peritore, A.F., D\u2019Amico, R., Gugliandolo, E., Crupi, R., Genovese, T., Evangelista, M., and Di Paola, R. (2020). The Protective Effects of Pre- and Post-Administration of Micronized Palmitoylethanolamide Formulation on Postoperative Pain in Rats. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207700"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1096\/fj.201902040R","article-title":"Plumericin prevents intestinal inflammation and oxidative stress in vitro and in vivo","volume":"34","author":"Rapa","year":"2019","journal-title":"FASEB J."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Siracusa, R., Fusco, R., Peritore, A.F., Cordaro, M., D\u2019Amico, R., Genovese, T., Gugliandolo, E., Crupi, R., Smeriglio, A., and Mandalari, G. (2020). The Antioxidant and Anti-Inflammatory Properties of Anacardium occidentale L. Cashew Nuts in a Mouse Model of Colitis. Nutrients, 12.","DOI":"10.3390\/nu12030834"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1124\/mol.116.105668","article-title":"Adelmidrol, a Palmitoylethanolamide Analogue, as a New Pharmacological Treatment for the Management of Inflammatory Bowel Disease","volume":"90","author":"Cordaro","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3389\/fneur.2017.00233","article-title":"Anti-Inflammatory and Neuroprotective Effects of Co-UltraPEALut in a Mouse Model of Vascular Dementia","volume":"6","author":"Siracusa","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2174\/1871527319666200107094732","article-title":"The Role of Annexin A1 and Formyl Peptide Receptor 2\/3 Signaling in Chronic Corticosterone-Induced Depression-Like behaviors and Impairment in Hippocampal-Dependent Memory","volume":"19","author":"Peritore","year":"2020","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Esposito, E., Campolo, M., Casili, G., Lanza, M., Franco, D., Filippone, A., Peritore, A.F., and Cuzzocrea, S. (2018). Protective Effects of Xyloglucan in Association with the Polysaccharide Gelose in an Experimental Model of Gastroenteritis and Urinary Tract Infections. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071844"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ejphar.2016.03.033","article-title":"A new co-micronized composite containing palmitoylethanolamide and polydatin shows superior oral efficacy compared to their association in a rat paw model of carrageenan-induced inflammation","volume":"5","author":"Esposito","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1096\/fj.201901584RR","article-title":"Effect of N-palmitoylethanolamine-oxazoline on comorbid neuropsychiatric disturbance associated with inflammatory bowel disease","volume":"34","author":"Cordaro","year":"2020","journal-title":"FASEB J."},{"key":"ref_73","first-page":"1688","article-title":"The activation of BDNF reduced inflammation in a spinal cord injury model by TrkB\/p38 MAPK signaling","volume":"17","author":"Liang","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13041-019-0523-7","article-title":"Silencing of microRNA-146a alleviates the neural damage in temporal lobe epilepsy by down-regulating Notch-1","volume":"12","author":"Huang","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1186\/s13075-019-2048-y","article-title":"Safety and efficacy of a new micronized formulation of the ALIAmide palmitoylglucosamine in preclinical models of inflammation and osteoarthritis pain","volume":"21","author":"Cordaro","year":"2019","journal-title":"Arthritis Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"31355","DOI":"10.18632\/oncotarget.25823","article-title":"Absence of formyl peptide receptor 1 causes endometriotic lesion regression in a mouse model of surgically-induced endometriosis","volume":"9","author":"Fusco","year":"2018","journal-title":"Oncotarget"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/pm\/pnx114","article-title":"Evidence of Altered Trigeminal Nociception in an Animal Model of Fibromyalgia","volume":"19","author":"Nazeri","year":"2017","journal-title":"Pain Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"9251","DOI":"10.1007\/s12035-018-1064-2","article-title":"2-Pentadecyl-2-Oxazoline Reduces Neuroinflammatory Environment in the MPTP Model of Parkinson Disease","volume":"55","author":"Cordaro","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"160","DOI":"10.33594\/000000353","article-title":"Physiological and Biochemical Changes in NRF2 Pathway in Aged Animals Subjected to Brain Injury","volume":"55","author":"Cordaro","year":"2021","journal-title":"Cell. Physiol. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/12\/6471\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:17:13Z","timestamp":1760163433000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/12\/6471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,16]]},"references-count":79,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22126471"],"URL":"https:\/\/doi.org\/10.3390\/ijms22126471","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,16]]}}}