{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:32:35Z","timestamp":1792701155474,"version":"4.5.0"},"reference-count":212,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"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 complex and heterogeneous clinical syndrome, mainly characterized by the presence of widespread pain, possibly associated with a variety of other symptoms. Fibromyalgia can have an extremely negative impact on the psychological, physical and social lives of people affected, sometimes causing patients to experience dramatically impaired quality of life. Nowadays, the diagnosis of fibromyalgia is still clinical, thus favoring diagnostic uncertainties and making its clear identification challenging to establish, especially in primary care centers. These difficulties lead patients to undergo innumerable clinical visits, investigations and specialist consultations, thus increasing their stress, frustration and even dissatisfaction. Unfortunately, research over the last 25 years regarding a specific biomarker for the diagnosis of fibromyalgia has been fruitless. The discovery of a reliable biomarker for fibromyalgia syndrome would be a critical step towards the early identification of this condition, not only reducing patient healthcare utilization and diagnostic test execution but also providing early intervention with guideline-based treatments. This narrative article reviews different metabolite alterations proposed as possible biomarkers for fibromyalgia, focusing on their associations with clinical evidence of pain, and highlights some new, promising areas of research in this context. Nevertheless, none of the analyzed metabolites emerge as sufficiently reliable to be validated as a diagnostic biomarker. Given the complexity of this syndrome, in the future, a panel of biomarkers, including subtype-specific biomarkers, could be considered as an interesting alternative research area.<\/jats:p>","DOI":"10.3390\/ijms241310443","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T01:49:32Z","timestamp":1687398572000},"page":"10443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Pain Biomarkers in Fibromyalgia Syndrome: Current Understanding and Future Directions"],"prefix":"10.3390","volume":"24","author":[{"given":"Martina","family":"Favretti","sequence":"first","affiliation":[{"name":"Rheumatology Unit, Department of Internal Clinical, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Iannuccelli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Internal Clinical, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-2065","authenticated-orcid":false,"given":"Manuela","family":"Di Franco","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Internal Clinical, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s11916-013-0356-5","article-title":"Worldwide Epidemiology of Fibromyalgia","volume":"17","author":"Queiroz","year":"2013","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_2","first-page":"S104","article-title":"Misdiagnosis in fibromyalgia: A multicentre study","volume":"29","author":"Iannuccelli","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","first-page":"90","article-title":"Fibromyalgia syndrome: Under-, over- and misdiagnosis","volume":"37","author":"Fitzcharles","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_4","first-page":"1065","article-title":"Fibromyalgia: One year in review 2022","volume":"40","author":"Giorgi","year":"2022","journal-title":"Clin. Exp. Rheumatol."},{"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":"160","DOI":"10.1002\/art.1780330203","article-title":"The american college of rheumatology 1990 Criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee","volume":"33","author":"Wolfe","year":"1990","journal-title":"Arthritis Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/acr.20140","article-title":"The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity","volume":"62","author":"Wolfe","year":"2010","journal-title":"Arthritis Care Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.semarthrit.2016.08.012","article-title":"2016 Revisions to the 2010\/2011 fibromyalgia diagnostic criteria","volume":"46","author":"Wolfe","year":"2016","journal-title":"Semin. Arthritis. Rheum."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/j.pain.0000000000001384","article-title":"Chronic pain as a symptom or a disease: The IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11)","volume":"160","author":"Treede","year":"2019","journal-title":"Pain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/j.pain.0000000000001390","article-title":"The IASP classification of chronic pain for ICD-11: Chronic primary pain","volume":"160","author":"Nicholas","year":"2019","journal-title":"Pain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1097\/j.pain.0000000000000507","article-title":"Do we need a third mechanistic descriptor for chronic pain states?","volume":"157","author":"Kosek","year":"2016","journal-title":"Pain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101415","DOI":"10.1016\/j.berh.2019.04.007","article-title":"New concepts of pain","volume":"33","author":"Trouvin","year":"2019","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1016\/S0140-6736(21)00392-5","article-title":"Nociplastic pain: Towards an understanding of prevalent pain conditions","volume":"397","author":"Fitzcharles","year":"2021","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1093\/brain\/awt053","article-title":"Small fibre pathology in patients with fibromyalgia syndrome","volume":"136","author":"Zeller","year":"2013","journal-title":"Brain"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1002\/art.38662","article-title":"Evidence of Abnormal Epidermal Nerve Fiber Density in Fibromyalgia: Clinical and Immunologic Implications","volume":"66","author":"Caro","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1002\/mus.24156","article-title":"Small nerve fiber involvement in patients referred for fibromyalgia","volume":"49","author":"Giannoccaro","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/mus.26131","article-title":"Fibromyalgia syndrome and small fiber, early or mild sensory polyneuropathy","volume":"58","author":"Lawson","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref_18","first-page":"448","article-title":"Fibromyalgia syndrome\u2014A laser-evoked potentials study unsupportive of small nerve fibre involvement","volume":"24","author":"Plaghki","year":"2019","journal-title":"Eur. J. Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1097\/j.pain.0000000000001920","article-title":"Small-fibre pathology has no impact on somatosensory system function in patients with fibromyalgia","volume":"161","author":"Fasolino","year":"2020","journal-title":"Pain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1007\/s10072-021-05806-x","article-title":"The puzzle of fibromyalgia between central sensitization syndrome and small fiber neuropathy: A narrative review on neurophysiological and morphological evidence","volume":"43","author":"Vecchio","year":"2022","journal-title":"Neurol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/ncprheum0091","article-title":"Mechanisms of Disease: Pain in fibromyalgia syndrome","volume":"2","author":"Staud","year":"2006","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nrrheum.2011.98","article-title":"Fibromyalgia: From pathophysiology to therapy","volume":"7","author":"Clauw","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s11916-002-0046-1","article-title":"Peripheral and central sensitization in fibromyalgia: Pathogenetic role","volume":"6","author":"Staud","year":"2002","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yam, M.F., Loh, Y.C., Tan, C.S., Adam, S.K., Manan, N.A., and Basir, R. (2018). General Pathways of Pain Sensation and the Major Neurotransmitters Involved in Pain Regulation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082164"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nrn2947","article-title":"Neuronal circuitry for pain processing in the dorsal horn","volume":"11","author":"Todd","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.brainresrev.2008.12.009","article-title":"Descending control of nociception: Specificity, recruitment and plasticity","volume":"60","author":"Heinricher","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s11571-016-9383-3","article-title":"A model of cooperative effect of AMPA and NMDA receptors in glutamatergic synapses","volume":"10","author":"Ventriglia","year":"2016","journal-title":"Cogn. Neurodyn."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.1460-9568.2010.07351.x","article-title":"Glutamate receptor phosphorylation and trafficking in pain plasticity in spinal cord dorsal horn","volume":"32","author":"Liu","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"ref_30","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_31","first-page":"1","article-title":"Gray Matter Abnormalities in Patients with Chronic Primary Pain: A Coordinate-Based Meta-Analysis","volume":"25","author":"Wang","year":"2022","journal-title":"Pain Physician"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.semarthrit.2014.01.001","article-title":"Central sensitization in fibromyalgia? A systematic review on structural and functional brain MRI","volume":"44","author":"Cagnie","year":"2014","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Siracusa, R., Di Paola, R., Cuzzocrea, S., and Impellizzeri, D. (2021). Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083891"},{"key":"ref_34","first-page":"S129","article-title":"Abnormal resting state functional connectivity of the periaqueductal grey in patients with fibromyalgia","volume":"34","author":"Truini","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Baraniuk, J.N., Whalen, G., Cunningham, J., and Clauw, D.J. (2004). Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain. BMC Musculoskelet. Disord., 5.","DOI":"10.1186\/1471-2474-5-48"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.neuroscience.2016.06.006","article-title":"Neurobiology of fibromyalgia and chronic widespread pain","volume":"338","author":"Sluka","year":"2016","journal-title":"Neuroscience"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/PSY.0b013e3182408f04","article-title":"Disrupted Functional Connectivity of the Pain Network in Fibromyalgia","volume":"74","author":"Cifre","year":"2012","journal-title":"Psychosom. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1126\/science.aaf8924","article-title":"Pain regulation by non-neuronal cells and inflammation","volume":"354","author":"Ji","year":"2016","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1097\/ALN.0000000000002130","article-title":"Neuroinflammation and Central Sensitization in Chronic and Widespread Pain","volume":"129","author":"Ji","year":"2018","journal-title":"Anesthesiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"665066","DOI":"10.3389\/fncel.2021.665066","article-title":"Involvement of Mast Cells in the Pathophysiology of Pain","volume":"15","author":"Mai","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3389\/fncel.2019.00345","article-title":"Mast Cells in Gut and Brain and Their Potential Role as an Emerging Therapeutic Target for Neural Diseases","volume":"13","author":"Traina","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1098\/rstb.2011.0391","article-title":"Mast cell\u2013glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide","volume":"367","author":"Skaper","year":"2012","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Salcman, B., Affleck, K., and Bulfone-Paus, S. (2021). P2X Receptor-Dependent Modulation of Mast Cell and Glial Cell Activities in Neuroinflammation. Cells, 10.","DOI":"10.3390\/cells10092282"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1177\/1073858416687249","article-title":"Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons","volume":"23","author":"Skaper","year":"2017","journal-title":"Neuroscientist"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"200","DOI":"10.12659\/MSMBR.893093","article-title":"Mast Cells and Neuroinflammation","volume":"20","author":"Qian","year":"2014","journal-title":"Med. Sci. Monit. Basic Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nri3621","article-title":"Pathological pain and the neuroimmune interface","volume":"14","author":"Grace","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.pain.2013.06.022","article-title":"Glia and pain: Is chronic pain a gliopathy?","volume":"154","author":"Ji","year":"2013","journal-title":"Pain"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"739130","DOI":"10.3389\/fimmu.2021.739130","article-title":"PET Imaging of Neuroinflammation in Alzheimer\u2019s Disease","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1007\/s00415-021-10877-z","article-title":"Neuroinflammation in Parkinson\u2019s disease: A meta-analysis of PET imaging studies","volume":"269","author":"Zhang","year":"2021","journal-title":"J. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/S2215-0366(20)30255-8","article-title":"Neuroinflammation in psychiatric disorders: PET imaging and promising new targets","volume":"7","author":"Meyer","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.jad.2021.06.001","article-title":"Neuroinflammation in Major Depressive Disorder: A Review of PET Imaging Studies Examining the 18-kDa Translocator Protein","volume":"292","author":"Gritti","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1021\/acschemneuro.6b00056","article-title":"In Vivo Imaging of Human Neuroinflammation","volume":"7","author":"Albrecht","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1097\/j.pain.0000000000001815","article-title":"Magnetic resonance imaging of neuroinflammation in chronic pain: A role for astrogliosis?","volume":"161","author":"Jung","year":"2020","journal-title":"Pain"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"913","DOI":"10.3174\/ajnr.A0959","article-title":"Proton MR Spectroscopy in the Evaluation of Cerebral Metabolism in Patients with Fibromyalgia: Comparison with Healthy Controls and Correlation with Symptom Severity","volume":"29","author":"Petrou","year":"2008","journal-title":"Am. J. Neuroradiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00540-018-2579-4","article-title":"Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain","volume":"33","author":"Matsuda","year":"2018","journal-title":"J. Anesth."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrrheum.2015.100","article-title":"Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome","volume":"11","author":"Littlejohn","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1152\/physrev.00042.2017","article-title":"The Corticotropin-Releasing Factor Family: Physiology of the Stress Response","volume":"98","author":"Deussing","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.pneurobio.2009.04.003","article-title":"Stress-induced analgesia","volume":"88","author":"Butler","year":"2009","journal-title":"Prog. Neurobiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s12017-007-8018-6","article-title":"The Sympathetic Nervous System and Pain","volume":"10","author":"Schlereth","year":"2007","journal-title":"NeuroMol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/j.1749-6632.2009.05344.x","article-title":"Neuroendocrine immunology of fibromyalgia","volume":"1193","author":"Iannuccelli","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.pnpbp.2017.10.014","article-title":"Effects of stress on the corticolimbic system: Implications for chronic pain","volume":"87","year":"2018","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.neubiorev.2019.10.007","article-title":"The interaction between stress and chronic pain through the lens of threat learning","volume":"107","author":"Timmers","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.psyneuen.2016.05.017","article-title":"Dysfunctional stress responses in chronic pain","volume":"71","author":"Woda","year":"2016","journal-title":"Psychoneuroendocrinology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s11064-019-02805-5","article-title":"Possible Molecular Mediators Involved and Mechanistic Insight into Fibromyalgia and Associated Co-morbidities","volume":"44","author":"Singh","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_65","first-page":"1744806918819944","article-title":"Fibromyalgia: Genetics and epigenetics insights may provide the basis for the development of diagnostic biomarkers","volume":"15","author":"Gerra","year":"2018","journal-title":"Mol. Pain"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fimmu.2017.00276","article-title":"Lifetime Modulation of the Pain System via Neuroimmune and Neuroendocrine Interactions","volume":"8","author":"Zouikr","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4068\/cmj.2015.51.2.58","article-title":"Exploring Genetic Susceptibility to Fibromyalgia","volume":"51","author":"Park","year":"2015","journal-title":"Chonnam Med. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"984","DOI":"10.3904\/kjim.2016.207","article-title":"New insights into the genetics of fibromyalgia","volume":"32","author":"Park","year":"2017","journal-title":"Korean J. Intern. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1097\/FPC.0b013e3283560c46","article-title":"Catechol-O-methyltransferase gene polymorphism and chronic human pain: A systematic re-view and meta-analysis","volume":"22","year":"2012","journal-title":"Pharmacogenet. Genom."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00296-014-3075-2","article-title":"Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: A meta-analysis","volume":"35","author":"Lee","year":"2014","journal-title":"Rheumatol. Int."},{"key":"ref_71","first-page":"8489","article-title":"Meta-analysis reveals a lack of association between a common catechol-O-methyltransferase (COMT) polymorphism val\u00b9\u2075\u2078met and fibromyalgia","volume":"7","author":"Zhang","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"116532","DOI":"10.1016\/j.neuroimage.2020.116532","article-title":"Brain GABA and glutamate levels across pain conditions: A systematic literature review and meta-analysis of 1H-MRS studies using the MRS-Q quality assessment tool","volume":"210","author":"Peek","year":"2020","journal-title":"Neuroimage"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cophys.2019.06.006","article-title":"Chronic non-inflammatory muscle pain: Central and peripheral mediators","volume":"11","author":"Lesnak","year":"2019","journal-title":"Curr. Opin. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1111\/j.1468-2982.2004.00750.x","article-title":"Cerebrospinal Fluid Glutamate Levels in Chronic Migraine","volume":"24","author":"Peres","year":"2004","journal-title":"Cephalalgia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jpain.2007.05.002","article-title":"Increased Levels of Neurotrophins Are Not Specific for Chronic Migraine: Evidence From Primary Fibromyalgia Syndrome","volume":"8","author":"Sarchielli","year":"2007","journal-title":"J. Pain"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1002\/art.24849","article-title":"Elevated insular glutamate in fibromyalgia is associated with experimental pain","volume":"60","author":"Harris","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1002\/art.23223","article-title":"Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia","volume":"58","author":"Harris","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_78","first-page":"R134","article-title":"Localized 1H-NMR spectroscopy in patients with fibromyalgia: A controlled study of changes in cerebral glutamate\/glutamine, inositol, choline, and N-acetylaspartate","volume":"12","author":"Fayed","year":"2010","journal-title":"Thromb. Haemost."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1002\/art.27430","article-title":"Increased glutamate\/glutamine compounds in the brains of patients with fibromyalgia: A magnetic resonance spectroscopy study","volume":"62","author":"Collado","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.3174\/ajnr.A2550","article-title":"Metabolic Abnormalities in Pain-Processing Regions of Patients with Fibromyalgia: A 3T MR Spectroscopy Study","volume":"32","author":"Feraco","year":"2011","journal-title":"Am. J. Neuroradiol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Feraco, P., Nigro, S., Passamonti, L., Grecucci, A., Caligiuri, M.E., Gagliardo, C., and Bacci, A. (2020). Neurochemical Correlates of Brain Atrophy in Fibromyalgia Syndrome: A Magnetic Resonance Spectroscopy and Cortical Thickness Study. Brain Sci., 10.","DOI":"10.3390\/brainsci10060395"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1002\/ejp.1820","article-title":"3D magnetic resonance spectroscopic imaging reveals links between brain metabolites and multidimensional pain features in fibromyalgia","volume":"25","author":"Lee","year":"2021","journal-title":"Eur. J. Pain"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12264-016-0016-y","article-title":"Insular Cortex is Critical for the Perception, Modulation, and Chronification of Pain","volume":"32","author":"Lu","year":"2016","journal-title":"Neurosci. Bull."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/ar3136","article-title":"Elevated excitatory neurotransmitter levels in the fibromyalgia brain","volume":"12","author":"Harris","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1152\/physrev.00031.2013","article-title":"Tachykinins and Their Receptors: Contributions to Physiological Control and the Mechanisms of Disease","volume":"94","author":"Steinhoff","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.2174\/0929867043364748","article-title":"Tachykinins and Tachykinin Receptors: Structure and Activity Relationships","volume":"11","author":"Almeida","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/bs.irn.2017.06.008","article-title":"Substance P and the Neurokinin-1 Receptor: The New CRF","volume":"136","author":"Schank","year":"2017","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/978-3-540-79090-7_13","article-title":"The Role of Peptides in Central Sensitization","volume":"194","author":"Seybold","year":"2009","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1002\/jcp.25993","article-title":"Nociceptor plasticity: A closer look","volume":"233","author":"Pace","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.neuron.2019.01.034","article-title":"Substance P and Inflammatory Pain: Getting It Wrong and Right Simultaneously","volume":"101","author":"Navratilova","year":"2019","journal-title":"Neuron"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.neuron.2019.01.012","article-title":"A Mast-Cell-Specific Receptor Mediates Neurogenic Inflammation and Pain","volume":"101","author":"Green","year":"2019","journal-title":"Neuron"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0304-3959(88)90019-X","article-title":"Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: New features for diagnosis","volume":"32","author":"Helle","year":"1988","journal-title":"Pain"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1002\/art.1780371106","article-title":"Elevated cerebrospinal fluid levels of substance p in patients with the fibromyalgia syndrome","volume":"37","author":"Russell","year":"1994","journal-title":"Arthritis Rheum."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1007\/s003930050238","article-title":"Neurochemical pathogenesis of fibromyalgia","volume":"57","author":"Russell","year":"1998","journal-title":"Z. Rheumatol."},{"key":"ref_95","first-page":"1802","article-title":"Plasma substance P levels in fibrositis","volume":"15","author":"Reynolds","year":"1988","journal-title":"J. Rheumatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1124\/jpet.115.230060","article-title":"Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells","volume":"356","author":"Tsilioni","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/j.clinthera.2019.05.019","article-title":"Effects of an Extract of Salmon Milt on Symptoms and Serum TNF and Substance P in Patients With Fibromyalgia Syndrome","volume":"41","author":"Tsilioni","year":"2019","journal-title":"Clin. Ther."},{"key":"ref_98","first-page":"72","article-title":"Fibromyalgia Pain and Substance P Decrease and Sleep Improves After Massage Therapy","volume":"8","author":"Field","year":"2002","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1093\/pm\/pnx263","article-title":"Effects of Acupuncture Treatment on Fibromyalgia Symptoms, Serotonin, and Substance P Levels: A Randomized Sham and Placebo-Controlled Clinical Trial","volume":"19","author":"Karatay","year":"2017","journal-title":"Pain Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s002960050051","article-title":"Pain treatment of fibromyalgia by acupuncture","volume":"18","author":"Sprott","year":"1998","journal-title":"Rheumatol. Int."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"R162","DOI":"10.1186\/ar3902","article-title":"Changes in pain and insulin-like growth factor 1 in fibromyalgia during exercise: The involvement of cerebrospinal inflammatory factors and neuropeptides","volume":"14","author":"Bjersing","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1146\/annurev-neuro-072116-031121","article-title":"Nerve Growth Factor and Pain Mechanisms","volume":"40","author":"Denk","year":"2017","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0304-3959(03)00012-5","article-title":"Injection of nerve growth factor into human masseter muscle evokes long-lasting mechanical allodynia and hyperalgesia","volume":"104","author":"Svensson","year":"2003","journal-title":"Pain"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.pain.2009.11.022","article-title":"NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity in human skin","volume":"148","author":"Rukwied","year":"2010","journal-title":"Pain"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/ejp.603","article-title":"Differential time course of NGF-induced hyperalgesia to heat versus mechanical and electrical stimulation in human skin","volume":"19","author":"Weinkauf","year":"2014","journal-title":"Eur. J. Pain"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00221-008-1531-5","article-title":"Spatial and temporal aspects of muscle hyperalgesia induced by nerve growth factor in humans","volume":"191","author":"Andersen","year":"2008","journal-title":"Exp. Brain Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1097\/AJP.0b013e3182048481","article-title":"Local Pain and Spreading Hyperalgesia Induced by Intramuscular Injection of Nerve Growth Factor Are Not Reduced by Local Anesthesia of the Muscle","volume":"27","author":"Gerber","year":"2011","journal-title":"Clin. J. Pain"},{"key":"ref_108","first-page":"566","article-title":"Enlarged Areas of Pain and Pressure Hypersensitivityby Spatially Distributed Intramuscular Injections ofLow-Dose Nerve Growth Factor","volume":"20","author":"Boudreau","year":"2018","journal-title":"J. Pain"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.nbd.2016.03.025","article-title":"Neurotrophic factors and their inhibitors in chronic pain treatment","volume":"97","author":"Kelleher","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.jpain.2010.12.016","article-title":"Breast Cancer-Induced Bone Remodeling, Skeletal Pain, and Sprouting of Sensory Nerve Fibers","volume":"12","author":"Bloom","year":"2011","journal-title":"J. Pain"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.2147\/JPR.S247472","article-title":"Nerve Growth Factor Signaling and Its Contribution to Pain","volume":"13","author":"Barker","year":"2020","journal-title":"J. Pain Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/imm.12717","article-title":"Nerve growth factor: A neuroimmune crosstalk mediator for all seasons","volume":"151","author":"Skaper","year":"2017","journal-title":"Immunology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/imr.12629","article-title":"Non-IgE mediated mast cell activation","volume":"282","author":"Redegeld","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/039463201402700103","article-title":"Nerve Growth Factor Interactions with Mast Cells","volume":"27","author":"Kritas","year":"2014","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1186\/s12974-020-02029-3","article-title":"Neurotransmitter and neuropeptide regulation of mast cell function: A systematic review","volume":"17","author":"Xu","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.yfrne.2009.05.002","article-title":"The NGF saga: From animal models of psychosocial stress to stress-related psychopathology","volume":"30","author":"Cirulli","year":"2009","journal-title":"Front. Neuroendocr."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s10194-021-01377-6","article-title":"Assessment of peripheral biomarkers potentially involved in episodic and chronic migraine: A case-control study with a focus on NGF, BDNF, VEGF, and PGE2","volume":"23","author":"Mozafarihashjin","year":"2022","journal-title":"J. Headache Pain"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1515\/hsz-2016-0280","article-title":"\u03b2-NGF and \u03b2-NGF receptor upregulation in blood and synovial fluid in osteoarthritis","volume":"398","author":"Montagnoli","year":"2017","journal-title":"Biol. Chem."},{"key":"ref_119","first-page":"1564","article-title":"Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia","volume":"26","author":"Giovengo","year":"1999","journal-title":"J. Rheumatol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"13667","DOI":"10.1038\/s41598-019-49403-7","article-title":"No evidence for altered plasma NGF and BDNF levels in fibromyalgia patients","volume":"9","author":"Baumeister","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"779","DOI":"10.2340\/16501977-2593","article-title":"Unaltered low nerve growth factor and high brain-derived neurotrophic factor levels in plasma from patients with fibromyalgia after a 15-week progressive resistance exercise","volume":"51","author":"Jablochkova","year":"2019","journal-title":"J. Rehabil. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1080\/08977190410001723308","article-title":"Brain-derived Neurotrophic Factor","volume":"22","author":"Binder","year":"2004","journal-title":"Growth Factors"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"107553","DOI":"10.1016\/j.pharmthera.2020.107553","article-title":"Targeting neurotrophic factors: Novel approaches to musculoskeletal pain","volume":"211","author":"Malfait","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.2174\/1570159X18666201116143422","article-title":"Interplay of BDNF and GDNF in the Mature Spinal Somatosensory System and Its Potential Therapeutic Relevance","volume":"19","author":"Ferrini","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"9857201","DOI":"10.1155\/2016\/9857201","article-title":"Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord","volume":"2016","author":"Garraway","year":"2016","journal-title":"Neural Plast."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00441-020-03253-2","article-title":"The physiology of regulated BDNF release","volume":"382","author":"Brigadski","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"753656","DOI":"10.1155\/2013\/753656","article-title":"Microglia and Spinal Cord Synaptic Plasticity in Persistent Pain","volume":"2013","author":"Taves","year":"2013","journal-title":"Neural Plast."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neures.2006.01.005","article-title":"BDNF in sensory neurons and chronic pain","volume":"55","author":"Obata","year":"2006","journal-title":"Neurosci. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neulet.2013.08.037","article-title":"The known knowns of microglia\u2013neuronal signalling in neuropathic pain","volume":"557","author":"Beggs","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/bs.pmbts.2014.11.010","article-title":"Commonalities Between Pain and Memory Mechanisms and Their Meaning for Understanding Chronic Pain","volume":"131","author":"Price","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1007\/s11064-010-0129-z","article-title":"Increased Plasma Levels of Brain Derived Neurotrophic Factor (BDNF) in Patients with Fibromyalgia","volume":"35","author":"Haas","year":"2010","journal-title":"Neurochem. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jpsychires.2006.02.007","article-title":"Increased BDNF serum concentration in fibromyalgia with or without depression or antidepressants","volume":"41","author":"Laske","year":"2007","journal-title":"J. Psychiatr. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.neulet.2019.05.021","article-title":"BDNF and serum S100B levels according the spectrum of structural pathology in chronic pain patients","volume":"706","author":"Stefani","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.neuint.2013.01.001","article-title":"Serum level of brain-derived neurotrophic factor in fibromyalgia syndrome correlates with depression but not anxiety","volume":"62","author":"Nugraha","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1007\/s00296-011-2348-2","article-title":"Brain-derived neurotrophic factor and exercise in fibromyalgia syndrome patients: A mini review","volume":"32","author":"Nugraha","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"e6775","DOI":"10.1590\/1414-431x20176775","article-title":"Inflammatory biomarkers responses after acute whole body vibration in fibromyalgia","volume":"51","author":"Ribeiro","year":"2018","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cyto.2016.05.011","article-title":"Evaluation of cytokines, oxidative stress markers and brain-derived neurotrophic factor in patients with fibromyalgia\u2014A controlled cross-sectional study","volume":"84","author":"Ranzolin","year":"2016","journal-title":"Cytokine"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1007\/s10067-022-06133-y","article-title":"Gender influence on clinical manifestations, depressive symptoms and brain-derived neurotrophic factor (BDNF) serum levels in patients affected by fibromyalgia","volume":"41","author":"Iannuccelli","year":"2022","journal-title":"Clin. Rheumatol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1113\/expphysiol.2009.048512","article-title":"Evidence for a release of brain-derived neurotrophic factor from the brain during exercise","volume":"94","author":"Rasmussen","year":"2009","journal-title":"Exp. Physiol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1055\/s-0037-1613072","article-title":"Brain-derived Neurotrophic Factor Is Stored in Human Platelets and Released by Agonist Stimulation","volume":"87","author":"Fujimura","year":"2002","journal-title":"Thromb. Haemost."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1007\/s00125-009-1364-1","article-title":"Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase","volume":"52","author":"Matthews","year":"2009","journal-title":"Diabetologia"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.neuropharm.2015.10.034","article-title":"BDNF\u2014A Key Transducer of Antidepressant Effects","volume":"102","author":"Monteggia","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Bidari, A., Ghavidel-Parsa, B., and Gharibpoor, F. (2022). Comparison of the serum brain-derived neurotrophic factor (BDNF) between fibromyalgia and nociceptive pain groups; and effect of duloxetine on the BDNF level. BMC Musculoskelet. Disord., 23.","DOI":"10.1186\/s12891-022-05369-8"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1744-8069-10-46","article-title":"Higher Serum S100B and BDNF Levels are Correlated with a Lower Pressure-Pain Threshold in Fibromyalgia","volume":"10","author":"Zanette","year":"2014","journal-title":"Mol. Pain"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3389\/fnhum.2016.00357","article-title":"Motor Cortex Excitability and BDNF Levels in Chronic Musculoskeletal Pain According to Structural Pathology","volume":"10","author":"Caumo","year":"2016","journal-title":"Front. Hum. Neurosci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1177\/2049463720920760","article-title":"Mapping of predictors of the disengagement of the descending inhibitory pain modulation system in fibromyalgia: An exploratory study","volume":"15","author":"Soldatelli","year":"2020","journal-title":"Br. J. Pain"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"6541798","DOI":"10.1155\/2020\/6541798","article-title":"Current and Emerging Pharmacotherapy for Fibromyalgia","volume":"2020","author":"Tzadok","year":"2020","journal-title":"Pain Res. Manag."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/AJP.0000000000000079","article-title":"Long-term Evaluation of Opioid Treatment in Fibromyalgia","volume":"31","author":"Peng","year":"2015","journal-title":"Clin. J. Pain"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e13913","DOI":"10.1097\/MD.0000000000013913","article-title":"Association between initial opioid use and response to a brief interdisciplinary treatment program in fibromyalgia","volume":"98","author":"Hwang","year":"2019","journal-title":"Medicine"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/j.1526-4637.2009.00613.x","article-title":"Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study","volume":"10","author":"Younger","year":"2009","journal-title":"Pain Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/art.37734","article-title":"Low-dose naltrexone for the treatment of fibromyalgia: Findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels","volume":"65","author":"Younger","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Parkitny, L., and Younger, J. (2017). Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia. Biomedicines, 5.","DOI":"10.3390\/biomedicines5020016"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"10000","DOI":"10.1523\/JNEUROSCI.2849-07.2007","article-title":"Decreased Central \u03bc-Opioid Receptor Availability in Fibromyalgia","volume":"27","author":"Harris","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1097\/j.pain.0000000000000633","article-title":"Endogenous opioidergic dysregulation of pain in fibromyalgia: A PET and fMRI study","volume":"157","author":"Schrepf","year":"2016","journal-title":"Pain"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"512","DOI":"10.3389\/fnins.2020.00512","article-title":"Cortical Binding Potential of Opioid Receptors in Patients With Fibromyalgia Syndrome and Reduced Systemic Interleukin-4 Levels\u2014A Pilot Study","volume":"14","author":"Buchholz","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Brejchova, J., Holan, V., and Svoboda, P. (2020). Expression of Opioid Receptors in Cells of the Immune System. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010315"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.bbi.2016.04.018","article-title":"Leukocyte opioid receptors mediate analgesia via Ca2+-regulated release of opioid peptides","volume":"57","author":"Celik","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"300","DOI":"10.3389\/fimmu.2020.00300","article-title":"Opioid Receptors in Immune and Glial Cells\u2014Implications for Pain Control","volume":"11","author":"Machelska","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Raffaeli, W., Malafoglia, V., Bonci, A., Tenti, M., Ilari, S., Gremigni, P., Iannuccelli, C., Gioia, C., Di Franco, M., and Mollace, V. (2020). Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041499"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Malafoglia, V., Ilari, S., Gioia, C., Vitiello, L., Tenti, M., Iannuccelli, C., Cristiani, C.M., Garofalo, C., Passacatini, L.C., and Viglietto, G. (2023). An Observational Study on Chronic Pain Biomarkers in Fibromyalgia and Osteoarthritis Patients: Which Role for Mu Opioid Receptor\u2019s Expression on NK Cells?. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030931"},{"key":"ref_161","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_162","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fncel.2018.00035","article-title":"Potential Mechanisms Underlying Centralized Pain and Emerging Therapeutic Interventions","volume":"12","author":"Nicol","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3109\/03009749709105321","article-title":"Dermal IgG Deposits and Increase of Mast Cells in Patients with Fibromyalgia\u2014Relevant Findings or Epiphenomena?","volume":"26","author":"Enestrbm","year":"1997","journal-title":"Scand. J. Rheumatol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s10067-010-1474-7","article-title":"Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia patients","volume":"29","author":"Blanco","year":"2010","journal-title":"Clin. Rheumatol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1097\/AJP.0000000000000169","article-title":"Mast Cell Stabilizer (Ketotifen) in Fibromyalgia: Phase 1 Randomized Controlled Clinical Trial","volume":"31","author":"Ang","year":"2015","journal-title":"Clin. J. Pain"},{"key":"ref_166","first-page":"146","article-title":"Detection of interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha in skin of patients with fibromyalgia","volume":"30","author":"Salemi","year":"2003","journal-title":"J. Rheumatol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"\u00dc\u00e7eyler, N., Kewenig, S., Kafke, W., Kittel-Schneider, S., and Sommer, C. (2014). Skin cytokine expression in patients with fibromyalgia syndrome is not different from controls. BMC Neurol., 14.","DOI":"10.1186\/s12883-014-0185-0"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"\u00dc\u00e7eyler, N., H\u00e4user, W., and Sommer, C. (2011). Systematic review with meta-analysis: Cytokines in fibromyalgia syndrome. BMC Musculoskelet. Disord., 12.","DOI":"10.1186\/1471-2474-12-245"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.1093\/rheumatology\/keab146","article-title":"Is fibromyalgia associated with a unique cytokine profile? A systematic review and meta-analysis","volume":"60","author":"Srivastava","year":"2021","journal-title":"Rheumatology"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1097\/j.pain.0000000000002510","article-title":"Potential role of blood biomarkers in patients with fibromyalgia: A systematic review with meta-analysis","volume":"163","author":"Kumbhare","year":"2021","journal-title":"Pain"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1111\/j.1526-4637.2011.01179.x","article-title":"MCP-1 and IL-8 as Pain Biomarkers in Fibromyalgia: A Pilot Study","volume":"12","author":"Ang","year":"2011","journal-title":"Pain Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/AJP.0b013e31817e13a3","article-title":"The Role of IL-8 in Patients With Fibromyalgia: A prospective longitudinal study of 6 months","volume":"25","author":"Wang","year":"2009","journal-title":"Clin. J. Pain"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jneuroim.2011.10.013","article-title":"Evidence of central inflammation in fibromyalgia\u2014Increased cerebrospinal fluid interleukin-8 levels","volume":"242","author":"Kadetoff","year":"2012","journal-title":"J. Neuroimmunol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jneuroim.2015.02.002","article-title":"Evidence of different mediators of central inflammation in dysfunctional and inflammatory pain\u2014Interleukin-8 in fibromyalgia and interleukin-1 \u03b2 in rheumatoid arthritis","volume":"280","author":"Kosek","year":"2015","journal-title":"J. Neuroimmunol."},{"key":"ref_175","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_176","doi-asserted-by":"crossref","first-page":"920517","DOI":"10.1155\/2012\/920517","article-title":"Pentraxin 3(PTX 3): An Endogenous Modulator of the Inflammatory Response","volume":"2012","author":"Kunes","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3109\/08916934.2011.611549","article-title":"Long pentraxin 3 (PTX3) in the light of its structure, mechanism of action and clinical implications","volume":"45","author":"Hrycek","year":"2012","journal-title":"Autoimmunity"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.imlet.2014.04.012","article-title":"The yin-yang of long pentraxin PTX3 in inflammation and immunity","volume":"161","author":"Daigo","year":"2014","journal-title":"Immunol. Lett."},{"key":"ref_179","first-page":"S142","article-title":"Pentraxin 3 levels in women with fibromyalgia","volume":"33","author":"Skare","year":"2015","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_180","first-page":"S151","article-title":"Reply to \u2018PTX-3 release is increased by monocytes from patients with primary fibromyalgia without major depression\u2019 by J.J. Garcia et al","volume":"34","author":"Skare","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_181","first-page":"S150","article-title":"PTX-3 release is increased by monocytes from patients with primary fibromyalgia without major depression","volume":"34","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/5584_2019_427","article-title":"Physiological and Therapeutic Roles of Neuropeptide Y on Biological Functions","volume":"1237","author":"Shende","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/emmm.201000100","article-title":"Therapeutic potential of neuropeptide Y (NPY) receptor ligands","volume":"2","author":"Brothers","year":"2010","journal-title":"EMBO Mol. Med."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.neuroscience.2017.08.050","article-title":"Neuropeptide Y and its Involvement in Chronic Pain","volume":"387","author":"Woldbye","year":"2018","journal-title":"Neuroscience"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"101894","DOI":"10.1016\/j.pneurobio.2020.101894","article-title":"Targeting spinal neuropeptide Y1 receptor-expressing interneurons to alleviate chronic pain and itch","volume":"196","author":"Nelson","year":"2020","journal-title":"Prog. Neurobiol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0149-7634(01)00066-5","article-title":"The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y","volume":"26","author":"Kask","year":"2002","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.npep.2015.09.008","article-title":"Neuropeptide Y: A stressful review","volume":"55","author":"Reichmann","year":"2016","journal-title":"Neuropeptides"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/j.1749-6632.2009.05365.x","article-title":"Pathophysiology of fibromyalgia: A comparison with the tension-type headache, a localized pain syndrome","volume":"1193","author":"Iannuccelli","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"580378","DOI":"10.3389\/fimmu.2020.580378","article-title":"Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect","volume":"11","author":"Chen","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1002\/art.1780371105","article-title":"Hypothalamic\u2013pituitary\u2013adrenal axis perturbations in patients with fibromyalgia","volume":"37","author":"Crofford","year":"1994","journal-title":"Arthritis Rheum."},{"key":"ref_191","first-page":"R28","article-title":"Serum neuropeptides in patients with both fibromyalgia (FMS) and chronic fatigue syndrome (CFS)","volume":"79","author":"Claw","year":"1995","journal-title":"J. Musculoskelet. Pain"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/ar2212","article-title":"Dysautonomia, fibromyalgia and reflex dystrophy","volume":"9","author":"Eisinger","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_193","first-page":"S75","article-title":"Autonomic dysfunction and neuropeptide Y in fibromyalgia","volume":"27","author":"Iannuccelli","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S1090-3801(99)90185-4","article-title":"Elevated plasma levels of neuropeptide Y in female fibromyalgia patients","volume":"3","author":"Anderberg","year":"1999","journal-title":"Eur. J. Pain"},{"key":"ref_195","first-page":"904967","article-title":"Vitamin D and Pain: Vitamin D and Its Role in the Aetiology and Maintenance of Chronic Pain States and Associated Comorbidities","volume":"2015","author":"Shipton","year":"2015","journal-title":"Pain Res. Treat."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.jcot.2019.07.004","article-title":"Vitamin D for skeletal and non-skeletal health: What we should know","volume":"10","author":"Charoenngam","year":"2019","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Karras, S., Rapti, E., Matsoukas, S., and Kotsa, K. (2016). Vitamin D in Fibromyalgia: A Causative or Confounding Biological Interplay?. Nutrients, 8.","DOI":"10.3390\/nu8060343"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"820","DOI":"10.3389\/fimmu.2020.00820","article-title":"Vitamin D and Its Potential Interplay With Pain Signaling Pathways","volume":"11","author":"Habib","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Ellis, S.D., Kelly, S.T., Shurlock, J.H., and Hepburn, A.L.N. (2018). The role of vitamin D testing and replacement in fibromyalgia: A systematic literature review. BMC Rheumatol., 2.","DOI":"10.1186\/s41927-018-0035-6"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3344\/kjp.2017.30.4.250","article-title":"Vitamin D and fibromyalgia: A meta-analysis","volume":"30","author":"Makrani","year":"2017","journal-title":"Korean J. Pain"},{"key":"ref_201","first-page":"E877","article-title":"Is Serum Hypovitaminosis D Associated with Chronic Widespread Pain Including Fibromyalgia? A Meta-analysis of Observational Studies","volume":"18","author":"Hsiao","year":"2015","journal-title":"Pain Physician"},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Joustra, M.L., Minovic, I., Janssens, K.A.M., Bakker, S.J.L., and Rosmalen, J.G.M. (2017). Vitamin and mineral status in chronic fatigue syndrome and fibromyalgia syndrome: A systematic review and meta-analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176631"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/nutrit\/nuz033","article-title":"Is hypovitaminosis D associated with fibromyalgia? A systematic review","volume":"78","author":"Martins","year":"2020","journal-title":"Nutr. Rev."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s42399-021-01105-w","article-title":"Prevalence of Vitamin D Deficiency and Its Relationship with Clinical Outcomes in Patients with Fibromyalgia: A Systematic Review of the Literature","volume":"4","author":"Ali","year":"2022","journal-title":"SN Compr. Clin. Med."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"25208","DOI":"10.52965\/001c.25208","article-title":"The Role of Vitamin D in the Management of Chronic Pain in Fibromyalgia: A Narrative Review","volume":"9","author":"Haddad","year":"2021","journal-title":"Health Psychol. Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1093\/nutrit\/nuy009","article-title":"Relationship between the gut microbiome and brain function","volume":"76","author":"Mohajeri","year":"2018","journal-title":"Nutr. Rev."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.pharmthera.2015.11.012","article-title":"Gut microbiome in health and disease: Linking the microbiome\u2013gut\u2013brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases","volume":"158","author":"Ghaisas","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The Microbiota-Gut-Brain Axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.bja.2019.07.026","article-title":"Pain regulation by gut microbiota: Molecular mechanisms and therapeutic potential","volume":"123","author":"Guo","year":"2019","journal-title":"Br. J. Anaesth."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.ebiom.2019.07.031","article-title":"Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia","volume":"46","author":"Abecia","year":"2019","journal-title":"Ebiomedicine"},{"key":"ref_211","first-page":"99","article-title":"Gut microbiome: Pertinence in fibromyalgia","volume":"38","author":"Minerbi","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Erdrich, S., Hawrelak, J.A., Myers, S.P., and Harnett, J.E. (2020). Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review. BMC Musculoskelet. Disord., 21.","DOI":"10.1186\/s12891-020-03201-9"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:57:58Z","timestamp":1760126278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/10443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,21]]},"references-count":212,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241310443"],"URL":"https:\/\/doi.org\/10.3390\/ijms241310443","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,21]]}}}