{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:08:27Z","timestamp":1793909307241,"version":"4.8.0"},"reference-count":81,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T00:00:00Z","timestamp":1653868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Fibromyalgia is a clinical condition that affects 1% to 5% of the population. No proper therapy has been currently found. It has been described that inflammation plays a central role in the nerve sensitizations that characterize the pathology. Methods: This paper aimed to evaluate the efficacy of etanercept and infliximab in the management of pain sensitization. Fibromyalgia was induced by three injections once a day of reserpine at the dose of 1 mg\/kg. Etanercept (3 mg\/kg) and infliximab (10 mg\/kg) were administered the day after the last reserpine injection and then 5 days after that. Behavioral analyses were conducted once a week, and molecular investigations were performed at the end of the experiment. Results: Our data confirmed the major effect of infliximab administration as compared to etanercept: infliximab administration strongly reduced pain sensitization in thermal hyperalgesia and mechanical allodynia. From the molecular point of view, infliximab reduced the activation of microglia and astrocytes and the expression of the purinergic P2X7 receptor ubiquitously expressed on glia and neurons. Downstream of the P2X7 receptor, infliximab also reduced p38-MAPK overexpression induced by the reserpine administration. Conclusion: Etanercept and infliximab treatment caused a significant reduction in pain. In particular, rats that received infliximab showed less pain sensitization. Moreover, infliximab reduced the activation of microglia and astrocytes, reducing the expression of the purinergic receptor P2X7 and p38-MAPK pathway.<\/jats:p>","DOI":"10.3390\/ijms23116139","type":"journal-article","created":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T10:05:14Z","timestamp":1653905114000},"page":"6139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["RETRACTED: Role of Etanercept and Infliximab on Nociceptive Changes Induced by the Experimental Model of Fibromyalgia"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-0043","authenticated-orcid":false,"given":"Marika","family":"Cordaro","sequence":"first","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\/0000-0001-7868-2505","authenticated-orcid":false,"given":"Rosalba","family":"Siracusa","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-3871","authenticated-orcid":false,"given":"Ramona","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3335-7327","authenticated-orcid":false,"given":"Tiziana","family":"Genovese","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Franco","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ylenia","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7563-9832","authenticated-orcid":false,"given":"Davide","family":"Di Paola","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 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, Viale Ferdinando Stagno D\u2019Alcontres 31, 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, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 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 Veterinary Sciences, University of Messina, 98168 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 Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Maffei, M.E. (2020). Fibromyalgia: Recent Advances in Diagnosis, Classification, Pharmacotherapy and Alternative Remedies. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217877"},{"key":"ref_2","first-page":"e18692","article-title":"Diagnostic Challenges and Management of Fibromyalgia","volume":"13","author":"Qureshi","year":"2021","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.reuma.2020.02.003","article-title":"Physiopathology of fibromyalgia","volume":"16","year":"2020","journal-title":"Reumatol. Clin. (Engl. Ed.)"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1744806918819944","DOI":"10.1177\/1744806918819944","article-title":"Fibromyalgia: Genetics and epigenetics insights may provide the basis for the development of diagnostic biomarkers","volume":"15","author":"Gerra","year":"2019","journal-title":"Mol. Pain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/s41584-020-00506-w","article-title":"Fibromyalgia: An update on clinical characteristics, aetiopathogenesis and treatment","volume":"16","author":"Giorgi","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.jpain.2009.06.012","article-title":"Central sensitization: A generator of pain hypersensitivity by central neural plasticity","volume":"10","author":"Latremoliere","year":"2009","journal-title":"J. Pain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"ITC33","DOI":"10.7326\/AITC202003030","article-title":"Fibromyalgia","volume":"172","author":"Bair","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/1099800411424204","article-title":"Psychoneuroimmunological Relationships in Women with Fibromyalgia","volume":"15","author":"Menzies","year":"2014","journal-title":"Biol. Res. Nurs."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/j.amjmed.2009.09.008","article-title":"Pathophysiology of Fibromyalgia","volume":"122","author":"Bradley","year":"2009","journal-title":"Am. J. Med."},{"key":"ref_10","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.\u2014Drug Targets"},{"key":"ref_11","first-page":"576","article-title":"Altered profile of chemokines in fibromyalgia patients","volume":"51","author":"Cidoncha","year":"2013","journal-title":"Ann. Clin. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Behm, F.G., Gavin, I.M., Karpenko, O., Lindgren, V., Gaitonde, S., Gashkoff, P.A., and Gillis, B.S. (2012). Unique immunologic patterns in fibromyalgia. BMC Clin. Pathol., 12.","DOI":"10.1186\/1472-6890-12-25"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.imlet.2014.01.009","article-title":"Fibromyalgia and cytokines","volume":"161","author":"Howard","year":"2014","journal-title":"Immunol. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s00296-019-04251-6","article-title":"Role of inflammation in the pathogenesis and treatment of fibromyalgia","volume":"39","author":"Benlidayi","year":"2019","journal-title":"Rheumatol. Int."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1212\/01.wnl.0000265062.92340.a5","article-title":"Differential expression of cytokines in painful and painless neuropathies","volume":"69","author":"Rogausch","year":"2007","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1136\/annrheumdis-2011-200373","article-title":"Adalimumab in acute sciatica reduces the long-term need for surgery: A 3-year follow-up of a randomised double-blind placebo-controlled trial","volume":"71","author":"Genevay","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jpain.2011.10.003","article-title":"Changes in plasma cytokines and their soluble receptors in complex regional pain syndrome","volume":"13","author":"Alexander","year":"2012","journal-title":"J. Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e13191","DOI":"10.1111\/dth.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":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1097\/00001756-200002280-00033","article-title":"Transgenic expression of TNF by astrocytes increases mechanical allodynia in a mouse neuropathy model","volume":"11","author":"DeLeo","year":"2000","journal-title":"NeuroReport"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1097\/BRS.0b013e3181733188","article-title":"Contralateral neuropathic pain and neuropathology in dorsal root ganglion and spinal cord following hemilateral nerve injury in rats","volume":"33","author":"Hatashita","year":"2008","journal-title":"Spine (Phila Pa 1976)"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/00005072-199305000-00006","article-title":"Pathology of experimental compression neuropathy producing hyperesthesia","volume":"52","author":"Sommer","year":"1993","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/0306-4522(93)90314-6","article-title":"Distribution and axonal relations of macrophages in a neuroma","volume":"55","author":"Risling","year":"1993","journal-title":"Neuroscience"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s11302-007-9071-1","article-title":"Modification of neuropathic pain sensation through microglial ATP receptors","volume":"3","author":"Inoue","year":"2007","journal-title":"Purinergic Signal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1111\/j.1526-4637.2009.00708.x","article-title":"Modulation of neuropathic pain by a glial-derived factor","volume":"10","author":"Adler","year":"2009","journal-title":"Pain Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1748-1716.2006.01568.x","article-title":"Could chronic pain and spread of pain sensation be induced and maintained by glial activation?","volume":"187","author":"Hansson","year":"2006","journal-title":"Acta Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.pain.2006.09.018","article-title":"Spinal microglia and neuropathic pain in young rats","volume":"128","author":"Moss","year":"2007","journal-title":"Pain"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ejpain.2008.04.017","article-title":"CCL2 is a key mediator of microglia activation in neuropathic pain states","volume":"13","author":"Thacker","year":"2009","journal-title":"Eur. J. Pain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1007\/BF01191706","article-title":"Rat Schwann cells can be induced to express major histocompatibility complex class II moleculesin vivo","volume":"21","author":"Bergsteinsdottir","year":"1992","journal-title":"J. Neurocytol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0006-8993(94)91425-7","article-title":"Production of prostanoids by Lewis rat Schwann cells in vitro","volume":"635","author":"Constable","year":"1994","journal-title":"Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1046\/j.1471-4159.1995.64020850.x","article-title":"Interleukin-6 production by schwann cells and induction in sciatic nerve injury","volume":"64","author":"Bolin","year":"1995","journal-title":"J. Neurochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1146\/annurev.neuro.24.1.1217","article-title":"Nerve growth factor signaling, neuroprotection, and neural repair","volume":"24","author":"Sofroniew","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/0024-3205(95)02047-M","article-title":"Cytokine-to-brain communication: A review & analysis of alternative mechanisms","volume":"57","author":"Watkins","year":"1995","journal-title":"Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrn2533","article-title":"Pathological and protective roles of glia in chronic pain","volume":"10","author":"Milligan","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1212\/WNL.56.10.1371","article-title":"TNF-alpha expression in painful and nonpainful neuropathies","volume":"56","author":"Empl","year":"2001","journal-title":"Neurology"},{"key":"ref_36","first-page":"357","article-title":"Expression of neuron-associated tumor necrosis factor alpha in the brain is increased during persistent pain","volume":"27","author":"Covey","year":"2002","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1365-2796.2004.01443.x","article-title":"Immune regulation of central nervous system functions: From sickness responses to pathological pain","volume":"257","author":"Watkins","year":"2005","journal-title":"J. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.ejpain.2008.08.001","article-title":"Effects of Etanercept and Minocycline in a rat model of spinal cord injury","volume":"13","author":"Marchand","year":"2009","journal-title":"Eur. J. Pain"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1136\/ard.2003.016451","article-title":"Efficacy of etanercept in the treatment of acute, severe sciatica: A pilot study","volume":"63","author":"Genevay","year":"2004","journal-title":"Ann. Rheum. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1097\/01.BRS.0000058944.38900.CE","article-title":"Tumor necrosis factor-alpha monoclonal antibody, infliximab, used to manage severe sciatica","volume":"28","author":"Karppinen","year":"2003","journal-title":"Spine (Phila Pa 1976)"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1097\/01.brs.0000141179.58778.6c","article-title":"Efficacy of infliximab for disc herniation-induced sciatica: One-year follow-up","volume":"29","author":"Korhonen","year":"2004","journal-title":"Spine (Phila Pa 1976)"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1097\/01.brs.0000245873.23876.1e","article-title":"The Treatment of disc herniation-induced sciatica with infliximab: One-year follow-up results of FIRST II, a randomized controlled trial","volume":"31","author":"Korhonen","year":"2006","journal-title":"Spine (Phila Pa 1976)"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/01.anes.0000267518.20363.0d","article-title":"A double-blind, placebo-controlled, dose\u2013response pilot study evaluating intradiscal etanercept in patients with chronic discogenic low back pain or lumbosacral radiculopathy","volume":"107","author":"Cohen","year":"2007","journal-title":"Anesthesiology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1097\/ALN.0b013e3181a05aa0","article-title":"Randomized, Double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica","volume":"110","author":"Cohen","year":"2009","journal-title":"Anesthesiology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.pain.2009.05.024","article-title":"Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia","volume":"146","author":"Nagakura","year":"2009","journal-title":"Pain"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1097\/01.j.pain.0000460334.49525.5e","article-title":"Peripheral and spinal mechanisms of nociception in a rat reserpine-induced pain model","volume":"156","author":"Taguchi","year":"2015","journal-title":"Pain"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.neulet.2016.01.025","article-title":"Effect of spinal monoaminergic neuronal system dysfunction on pain threshold in rats, and the analgesic effect of serotonin and norepinephrine reuptake inhibitors","volume":"615","author":"Tamano","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"38325","DOI":"10.1038\/srep38325","article-title":"Functional MRI of the Reserpine-Induced Putative Rat Model of Fibromyalgia Reveals Discriminatory Patterns of Functional Augmentation to Acute Nociceptive Stimuli","volume":"7","author":"Wells","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1007\/s10620-019-05577-8","article-title":"Coexistence of Alterations of Gastrointestinal Function and Mechanical Allodynia in the Reserpine-Induced Animal Model of Fibromyalgia","volume":"64","author":"Uchida","year":"2019","journal-title":"Dig. Dis. Sci."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/sj.bjp.0701732","article-title":"ATP stimulation of Ca2+-dependent plasminogen release from cultured microglia","volume":"123","author":"Inoue","year":"1998","journal-title":"Br. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.tins.2008.10.001","article-title":"Purinergic signalling in the nervous system: An overview","volume":"32","author":"Abbracchio","year":"2009","journal-title":"Trends Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7268","DOI":"10.4049\/jimmunol.174.11.7268","article-title":"Astrocyte-Derived ATP Induces Vesicle Shedding and IL-1\u03b2 Release from Microglia","volume":"174","author":"Bianco","year":"2005","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/glia.22358","article-title":"Purinergic receptors in microglia: Functional modal shifts of microglia mediated by P2 and P1 receptors","volume":"61","author":"Koizumi","year":"2013","journal-title":"Glia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/JNEUROSCI.3792-03.2004","article-title":"Production and Release of Neuroprotective Tumor Necrosis Factor by P2X7 Receptor-Activated Microglia","volume":"24","author":"Suzuki","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1476-9255-4-5","article-title":"The role of the purinergic P2X7 receptor in inflammation","volume":"4","author":"Lister","year":"2007","journal-title":"J. Inflamm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.expneurol.2006.01.003","article-title":"Increases in the activated forms of ERK 1\/2, p38 MAPK, and CREB are correlated with the expression of at-level mechanical allodynia following spinal cord injury","volume":"199","author":"Crown","year":"2006","journal-title":"Exp. Neurol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.expneurol.2008.05.025","article-title":"Activation of p38 MAP kinase is involved in central neuropathic pain following spinal cord injury","volume":"213","author":"Crown","year":"2008","journal-title":"Exp. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.neuroscience.2008.03.041","article-title":"Activation of microglia and p38 mitogen-activated protein kinase in the dorsal column nucleus contributes to tactile allodynia following peripheral nerve injury","volume":"153","author":"Terayama","year":"2008","journal-title":"Neuroscience"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/ALN.0b013e318190bc16","article-title":"Activation of p38 Mitogen-activated Protein Kinase in Spinal Microglia Contributes to Incision-induced Mechanical Allodynia","volume":"110","author":"Wen","year":"2009","journal-title":"Anesthesiology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3389\/fvets.2020.00136","article-title":"Protective Effect of Hydroxytyrosol Against Oxidative Stress Induced by the Ochratoxin in Kidney Cells: In vitro and in vivo Study","volume":"7","author":"Crupi","year":"2020","journal-title":"Front Vet Sci"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/BRS.0b013e318162340a","article-title":"Effect of etanercept, a tumor necrosis factor-alpha inhibitor, on neuropathic pain in the rat chronic constriction injury model","volume":"33","author":"Zanella","year":"2008","journal-title":"Spine (Phila Pa 1976)"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1124\/dmd.116.074807","article-title":"Interrelationships between Infliximab and Recombinant Tumor Necrosis Factor-alpha in Plasma Using Minimal Physiologically Based Pharmacokinetic Models","volume":"45","author":"Chen","year":"2017","journal-title":"Drug Metab Dispos"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1002\/jnr.23432","article-title":"Tumor necrosis factor-\u03b1 inhibitors alleviation of experimentally induced neuropathic pain is associated with modulation of TNF receptor expression","volume":"92","author":"Andrade","year":"2014","journal-title":"J. Neurosci. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e1933","DOI":"10.21769\/BioProtoc.1933","article-title":"Assessment of mechanical allodynia in rats using the electronic von frey test","volume":"6","author":"Ferrier","year":"2016","journal-title":"Bio-protocol"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cordaro, M., Siracusa, R., Fusco, R., D\u2019Amico, R., Peritore, A.F., Gugliandolo, E., Genovese, T., Scuto, M., Crupi, R., and Mandalari, G. (2020). Cashew (Anacardium occidentale L.) Nuts Counteract Oxidative Stress and Inflammation in an Acute Experimental Model of Carrageenan-Induced Paw Edema. Antioxidants (Basel), 9.","DOI":"10.3390\/antiox9080660"},{"key":"ref_67","first-page":"382","article-title":"Co-micronized Palmitoylethanolamide\/Polydatin Treatment Causes Endometriotic Lesion Regression in a Rodent Model of Surgically Induced Endometriosis","volume":"7","author":"Fusco","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_68","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_69","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_70","doi-asserted-by":"crossref","unstructured":"Fusco, R., Cordaro, M., Genovese, T., Impellizzeri, D., Siracusa, R., Gugliandolo, E., Peritore, A.F., D\u2019Amico, R., Crupi, R., and Cuzzocrea, S. (2020). Adelmidrol: A New Promising Antioxidant and Anti-Inflammatory Therapeutic Tool in Pulmonary Fibrosis. Antioxidants, 9.","DOI":"10.3390\/antiox9070601"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Fusco, R., Cordaro, M., Siracusa, R., Peritore, A.F., Gugliandolo, E., Genovese, T., D\u2019Amico, R., Crupi, R., Smeriglio, A., and Mandalari, G. (2020). Consumption of Anacardium Occidentale L. (Cashew Nuts) Inhibits Oxidative Stress through Modulation of the Nrf2\/HO-1 and NF-kB Pathways. Molecules, 25.","DOI":"10.3390\/molecules25194426"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Cordaro, M., Fusco, R., D\u2019Amico, R., Siracusa, R., Peritore, A.F., Gugliandolo, E., Genovese, T., Crupi, R., Mandalari, G., and Cuzzocrea, S. (2020). Cashew (Anacardium occidentale L.) Nuts Modulate the Nrf2 and NLRP3 Pathways in Pancreas and Lung after Induction of Acute Pancreatitis by Cerulein. Antioxidants, 9.","DOI":"10.3390\/antiox9100992"},{"key":"ref_73","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_74","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_75","doi-asserted-by":"crossref","unstructured":"Fusco, R., Gugliandolo, E., Campolo, M., Evangelista, M., Di Paola, R., and Cuzzocrea, S. (2017). Effect of a new formulation of micronized and ultramicronized N-palmitoylethanolamine in a tibia fracture mouse model of complex regional pain syndrome. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178553"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"590","DOI":"10.3389\/fneur.2018.00590","article-title":"Neuroprotective Effect of Artesunate in Experimental Model of Traumatic Brain Injury","volume":"9","author":"Gugliandolo","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_77","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_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-018-1303-5","article-title":"Effect of PEA-OXA on neuropathic pain and functional recovery after sciatic nerve crush","volume":"15","author":"Gugliandolo","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.nbd.2019.01.007","article-title":"N-Palmitoylethanolamine-oxazoline (PEA-OXA): A new therapeutic strategy to reduce neuroinflammation, oxidative stress associated to vascular dementia in an experimental model of repeated bilateral common carotid arteries occlusion","volume":"125","author":"Impellizzeri","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s13075-016-1189-5","article-title":"Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats","volume":"18","author":"Fusco","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_81","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"}],"updated-by":[{"DOI":"10.3390\/ijms27031519","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T00:00:00Z","timestamp":1653868800000}},{"DOI":"10.3390\/ijms27031519","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"record-id":"70226"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T09:03:20Z","timestamp":1770195800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,30]]},"references-count":81,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23116139"],"URL":"https:\/\/doi.org\/10.3390\/ijms23116139","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,30]]}}}