The Proteomics and Fibromyalgia: A Perspective on the Study of the Inflammatory Response in Fibromyalgia
Main Article Content
Jose Luis Maldonado-García, Dr
http://orcid.org/0000-0003-2694-1290
María Teresa Vega-Ramírez, Dra
http://orcid.org/0000-0003-2450-4927
Gilberto Pérez-Sanchez, Dr
http://orcid.org/0000-0003-3878-0631
Enrique Becerril-Villanueva, Dr
http://orcid.org/0000-0001-7210-9775
Samantha Alvarez-Herrera, Dra
http://orcid.org/0000-0001-9747-885X
Danelia Mendieta-Cabrera, Dra
Martha Moreno-Lafont, Dra
http://orcid.org/0000-0003-2896-5819
Lenin Pavón, Dr
http://orcid.org/0000-0002-6067-6868
http://orcid.org/0000-0003-2694-1290
María Teresa Vega-Ramírez, Dra
http://orcid.org/0000-0003-2450-4927
Gilberto Pérez-Sanchez, Dr
http://orcid.org/0000-0003-3878-0631
Enrique Becerril-Villanueva, Dr
http://orcid.org/0000-0001-7210-9775
Samantha Alvarez-Herrera, Dra
http://orcid.org/0000-0001-9747-885X
Danelia Mendieta-Cabrera, Dra
Martha Moreno-Lafont, Dra
http://orcid.org/0000-0003-2896-5819
Lenin Pavón, Dr
http://orcid.org/0000-0002-6067-6868
Abstract
Fibromyalgia (FM) is a chronic, non-degenerative disease characterized by widespread and sustained pain, sleep disturbances, physical exhaustion, and cognitive difficulties. The FM pathophysiology has not been completely clarified, and several theories have been postulated, among which is the dysregulation of the inflammatory response as a mediator of the painful phenomenon. In addition, it has been reported that FM patients present a rise of IL-6 and IL-8 serum levels; this fact has clinical relevance since these inflammatory molecules induce symptoms such as pain, fatigue, hyperalgesia, and allodynia.
Additionally, some studies have been carried out on the participation of leukocytes in the physiopathology of fibromyalgia; The evidence suggests that mast cells are the most relevant leukocytes in the pathophysiology of FM since they promote the release of pro-inflammatory cytokines in response to stimuli such as substance P or corticotropin-releasing hormone, which were elevated in patients.
The number of FM patients is increasing year after year around the world. For this reason, it is essential to study the proteins involved in the inflammatory response in fibromyalgia. Proteomic analysis techniques such as tandem mass tag (TMT) with isobaric labeling offer a hope to find biological markers that allow the study simultaneously the participation of multiple inflammatory proteins in FM patients, allowing the identification of biomarkers. Thus, the use of isobaric tagging will allow shortly to expand the knowledge of pathophysiology in fibromyalgia, helping to identify biomarkers to improve the diagnosis of the FM disease and increase the quality of life of patients and their families.
Keywords:
Fibromyalgia, leucocytes, cytokines, proteomics, tandem mass tag, isobaric label
Article Details
How to Cite
MALDONADO-GARCÍA, Jose Luis et al.
The Proteomics and Fibromyalgia: A Perspective on the Study of the Inflammatory Response in Fibromyalgia.
Medical Research Archives, [S.l.], v. 9, n. 8, aug. 2021.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2518>. Date accessed: 05 nov. 2024.
doi: https://doi.org/10.18103/mra.v9i8.2518.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Felipe D, Rodríguez G, Mendoza CA. Fisiopatología de la fibromialgia Physiopathology of fibromyalgia. Reum Clin. 2020;16(3):191-194. https://doi.org/10.1016/j.reuma.2020.02.003.
2. Jiménez MM, Javier F, Bosquet S. Neurastenia y fibromialgia: el enlace entre el sistema nervioso y la cultura en entidades clínicas complejas. En-claves del Pensam. 2017;11(22):51-74.
3. Häuser W, Sarzi-Puttini P, Fitzcharles M-A. Fibromyalgia syndrome: under-, over- and misdiagnosis. Clin Exp Rheumatol. 2019;37 Suppl 1(1):90-97. http://www.ncbi.nlm.nih.gov/pubmed/30747096.
4. Perrot S. If fibromyalgia did not exist, we should have invented it. A short history of a controversial syndrome. Reumatismo. 2012;64(4):186-193. doi:10.4081/reumatismo.2012.186
5. Häuser W, Ablin J, Fitzcharles MA, et al. Fibromyalgia. Nat Rev Dis Prim. 2015;1(August):1-16. doi:10.1038/nrdp.2015.22
6. Sarzi-Puttini P, Giorgi V, Marotto D, Atzeni F. Fibromyalgia: an update on clinical characteristics, aetiopathogenesis and treatment. Nat Rev Rheumatol. 2020;16(11):645-660. doi:10.1038/s41584-020-00506-w
7. Hackshaw K V. The Search for Biomarkers in Fibromyalgia. Diagnostics. 2021;11(2):156. doi:10.3390/diagnostics11020156
8. Peláez-Ballestas I, Sanin LH, Moreno-Montoya J, et al. Epidemiology of the rheumatic diseases in Mexico. A study of 5 regions based on the COPCORD methodology. J Rheumatol Suppl. 2011;86(SUPPL. 86):3-8. doi:10.3899/jrheum.100951
9. Choy E, Perrot S, Leon T, et al. A patient survey of the impact of fibromyalgia and the journey to diagnosis. BMC Health Serv Res. 2010;10:102. doi:10.1186/1472-6963-10-102
10. Gendelman O, Amital H, Bar-On Y, et al. Time to diagnosis of fibromyalgia and factors associated with delayed diagnosis in primary care. Best Pract Res Clin Rheumatol. 2018;32(4):489-499. doi:10.1016/j.berh.2019.01.019
11. Lacasse A, Bourgault P, Choinière M. Fibromyalgia-related costs and loss of productivity: A substantial societal burden. BMC Musculoskelet Disord. 2016;17(1). doi:10.1186/s12891-016-1027-6
12. Berger A, Dukes E, Martin S, Edelsberg J, Oster G. Characteristics and healthcare costs of patients with fibromyalgia syndrome. Int J Clin Pract. 2007;61(9):1498-1508. doi:10.1111/j.1742-1241.2007.01480.x
13. Guymer EK, Littlejohn GO, Brand CK, Kwiatek RA. Fibromyalgia onset has a high impact on work ability in Australians. Intern Med J. 2016;46(9):1069-1074. doi:10.1111/imj.13135
14. Núñez-nevárez K, López-betancourt A, Cisneros-pérez V. Labor Condition and Severity of Fibromyalgia Condición Laboral y Severidad de la Fibromialgia. Rev Red Inv Sal Trab. 2021;4(6):54-59.
15. González E, Elorza J, Failde I. Fibromyalgia and psychiatric comorbidity: their effect on the quality of life patients. Actas Esp Psiquiatr. 38(5):295-300. http://www.ncbi.nlm.nih.gov/pubmed/21117004. Accessed June 1, 2021.
16. Coskun Benlidayi I. Role of inflammation in the pathogenesis and treatment of fibromyalgia. Rheumatol Int. 2019;39(5):781-791. doi:10.1007/s00296-019-04251-6
17. Banfi G, Diani M, Pigatto PD, Reali E. T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives. Int J Mol Sci. 2020;21(4):1186. doi:10.3390/ijms21041186
18. Van West D, Maes M. Neuroendocrine and immune aspects of fibromyalgia. BioDrugs. 2001;15(8):521-531. doi:10.2165/00063030-200115080-00004
19. Bote ME, Garca JJ, Hinchado MD, Ortega E. Inflammatory/stress feedback dysregulation in women with fibromyalgia. Neuroimmunomodulation. 2012;19(6):343-351. doi:10.1159/000341664
20. Kadetoff D, Lampa J, Westman M, Andersson M, Kosek E. Evidence of central inflammation in fibromyalgia - Increased cerebrospinal fluid interleukin-8 levels. J Neuroimmunol. 2012;242(1-2):33-38. doi:10.1016/j.jneuroim.2011.10.013
21. Peck MM, Maram R, Mohamed A, et al. The Influence of Pro-inflammatory Cytokines and Genetic Variants in the Development of Fibromyalgia: A Traditional Review. Cureus. September 2020. doi:10.7759/cureus.10276
22. Totsch SK, Sorge RE. Immune system involvement in specific pain conditions. Mol Pain. 2017;13. doi:10.1177/1744806917724559
23. Theoharides TC, Tsilioni I, Bawazeer M. Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome. Front Cell Neurosci. 2019;13. doi:10.3389/fncel.2019.00353
24. Fries E, Hesse J, Hellhammer J, Hellhammer DH. A new view on hypocortisolism. Psychoneuroendocrinology. 2005;30(10):1010-1016. doi:10.1016/j.psyneuen.2005.04.006
25. Tsilioni I, Russell IJ, Stewart JM, Gleason RM, Theoharides TC. Neuropeptides CRH, SP, HK-1, and inflammatory cytokines IL-6 and TNF are increased in serum of patients with fibromyalgia syndrome, implicating mast cells. J Pharmacol Exp Ther. 2016;356(3):664-672. doi:10.1124/jpet.115.230060
26. Furer V, Hazan E, Mor A, et al. Elevated Levels of Eotaxin-2 in Serum of Fibromyalgia Patients. Pain Res Manag. 2018;2018. doi:10.1155/2018/7257681
27. Rodriguez-Pintó I, Agmon-Levin N, Howard A, Shoenfeld Y. Fibromyalgia and cytokines. Immunol Lett. 2014;161(2):200-203. doi:10.1016/j.imlet.2014.01.009
28. Andrés-Rodríguez L, Borràs X, Feliu-Soler A, et al. Peripheral immune aberrations in fibromyalgia: A systematic review, meta-analysis and meta-regression. Brain Behav Immun. 2020;87:881-889. doi:10.1016/j.bbi.2019.12.020
29. Mendieta D, la Cruz-Aguilera DL De, Barrera-Villalpando MI, et al. IL-8 and IL-6 primarily mediate the inflammatory response in fibromyalgia patients. J Neuroimmunol. 2016;290:22-25. doi:10.1016/j.jneuroim.2015.11.011
30. Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci. 2012;122(4):143-159. doi:10.1042/CS20110340
31. Zhou YQ, Liu Z, Liu ZH, et al. Interleukin-6: An emerging regulator of pathological pain. JNeuroinflammation. 2016;13(1). doi:10.1186/s12974-016-0607-6
32. Nordlind K, Eriksson L, Seiger Å, Bakhiet M. Expression of interleukin-6 in human dorsal root ganglion cells. Neurosci Lett. 2000;280(2):139-142. doi:10.1016/S0304-3940(00)00772-2
33. Yan J, Melemedjian OK, Price TJ, Dussor G. Sensitization of dural afferents underlies migraine-related behavior following meningeal application of interleukin-6 (IL-6). Mol Pain. 2012;8:1-9. doi:10.1186/1744-8069-8-6
34. Cunha FQ, Lorenzetti BB, Poole S, Ferreira SH. Interleukin‐8 as a mediator of sympathetic pain. Br J Pharmacol. 1991;104(3):765-767. doi:10.1111/j.1476-5381.1991.tb12502.x
35. Duarte H, Teixeira AL, Rocha NP, Domingues RB. Increased interictal serum levels of CXCL8/IL-8 and CCL3/MIP-1α in migraine. Neurol Sci. 2015;36(2):203-208. doi:10.1007/s10072-014-1931-1
36. Sommer C, Leinders M, Üçeyler N. Inflammation in the pathophysiology of neuropathic pain. Pain. 2018;159(3):595-602. doi:10.1097/j.pain.0000000000001122
37. Sluka KA, Clauw DJ. Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience. 2016;338:114-129. doi:10.1016/j.neuroscience.2016.06.006
38. Illescas-Montes R, Costela-Ruiz VJ, Melguizo-Rodríguez L, De Luna-Bertos E, Ruiz C, Ramos-Torrecillas J. Application of Salivary Biomarkers in the Diagnosis of Fibromyalgia. Diagnostics. 2021;11(1):63. doi:10.3390/diagnostics11010063
39. Singh L, Kaur A, Bhatti MS, Bhatti R. Possible Molecular Mediators Involved and Mechanistic Insight into Fibromyalgia and Associated Co-morbidities. Neurochem Res. 2019;44(7):1517-1532. doi:10.1007/s11064-019-02805-5
40. Wallace DJ, Linker‐Israeli M, Hallegua D, Silverman S, Silver D, Weisman MH. Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study. Rheumatology. 2001;40(7):743-749. doi:10.1093/rheumatology/40.7.743
41. Pernambuco AP, Schetino LPL, Alvim CC, et al. Increased levels of il-17a in patients with fibromyalgia. Clin Exp Rheumatol. 2013;31(SUPPL.79):60-63.
42. Ebbinghaus M, Natura G, Segond Von Banchet G, et al. Interleukin-17A is involved in mechanical hyperalgesia but not in the severity of murine antigen-induced arthritis. Sci Rep. 2017;7(1). doi:10.1038/s41598-017-10509-5
43. Sun C, Zhang J, Chen L, et al. IL-17 contributed to the neuropathic pain following peripheral nerve injury by promoting astrocyte proliferation and secretion of proinflammatory cytokines. Mol Med Rep. 2017;15(1):89-96. doi:10.3892/mmr.2016.6018
44. Jones KD, Gelbart T, Whisenant TC, et al. Genome-wide expression profiling in the peripheral blood of patients with fibromyalgia. Clin Exp Rheumatol. 2016;34(2 Suppl 96):S89-98. http://www.ncbi.nlm.nih.gov/pubmed/27157394.
45. Wang T, Yin J, Miller AH, Xiao C. A systematic review of the association between fatigue and genetic polymorphisms. Brain Behav Immun. 2017;62:230-244. doi:10.1016/j.bbi.2017.01.007
46. Chae J, Ng T, Yeo HL, et al. Impact of TNF-α (rs1800629) and IL-6 (rs1800795) Polymorphisms on Cognitive Impairment in Asian Breast Cancer Patients. Spencer J, ed. PLoS One. 2016;11(10):e0164204. doi:10.1371/journal.pone.0164204
47. Aouizerat BE, Dodd M, Lee K, et al. Preliminary evidence of a genetic association between tumor necrosis factor alpha and the severity of sleep disturbance and morning fatigue. Biol Res Nurs. 2009;11(1):27-41. doi:10.1177/1099800409333871
48. Ernberg M, Christidis N, Ghafouri B, et al. Effects of 15weeks of resistance exercise on pro-inflammatory cytokine levels in the vastus lateralis muscle of patients with fibromyalgia. Arthritis Res Ther. 2016;18(1). doi:10.1186/s13075-016-1041-y
49. Zabihiyeganeh M, Vafaee Afshar S, Amini Kadijani A, et al. The effect of cognitive behavioral therapy on the circulating proinflammatory cytokines of fibromyalgia patients: A pilot controlled clinical trial. Gen Hosp Psychiatry. 2019;57:23-28. doi:10.1016/j.genhosppsych.2019.01.003
50. Ernberg M, Christidis N, Ghafouri B, et al. Plasma cytokine levels in fibromyalgia and their response to 15 weeks of progressive resistance exercise or relaxation therapy. Mediators Inflamm. 2018;2018. doi:10.1155/2018/3985154
51. Parkitny L, Younger J. Reduced pro-inflammatory cytokines after eight weeks of low-dose naltrexone for Fibromyalgia. Biomedicines. 2017;5(2). doi:10.3390/biomedicines5020016
52. Conti P, Gallenga CE, Caraffa A, Ronconi G, Kritas SK. Impact of mast cells in fibromyalgia and low-grade chronic inflammation: Can IL-37 play a role? Dermatol Ther. 2020;33(1). doi:10.1111/dth.13191
53. Mastrangelo F, Gallenga CE. Low-Grade Chronic Inflammation Mediated by Mast Cells in Fibromyalgia: Role of IL-37.; 2018. https://www.researchgate.net/publication/324772237.
54. Hader N, Rimon D, Kinarty A, Lahat N. Altered interleukin‐2 secretion in patients with primary fibromyalgia syndrome. Arthritis Rheum. 1991;34(7):866-872. doi:10.1002/art.1780340712
55. Hernanz W, Valenzuela A, Quijada J, et al. Lymphocyte subpopulations in patients with primary fibromyalgia. J Rheumatol. 1994;21(11):2122-2124. https://pubmed.ncbi.nlm.nih.gov/7869321/. Accessed June 2, 2021.
56. Sugimoto C, Konno T, Wakao R, Fujita H, Fujita H, Wakao H. Mucosal-Associated invariant T Cell Is a potential marker to distinguish fibromyalgia syndrome from arthritis. PLoS One. 2015;10(4). doi:10.1371/journal.pone.0121124
57. Kaufmann I, Eisner C, Richter P, et al. Lymphocyte subsets and the role of Th1/Th2 balance in stressed chronic pain patients. Neuroimmunomodulation. 2007;14(5):272-280. doi:10.1159/000115041
58. Littlejohn G, Guymer E. Neurogenic inflammation in fibromyalgia. Semin Immunopathol. 2018;40(3):291-300. doi:10.1007/s00281-018-0672-2
59. Hunsucker SW, Accurso FJ, Duncan MW. Proteomics in Pediatric Research and Practice. Adv Pediatr. 2007;54(1):9-28. doi:10.1016/j.yapd.2007.03.003
60. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463-466. doi:10.1097/COH.0b013e32833ed17
61. Liu CW, Zhang Q. Isobaric Labeling-Based LC-MS/MS Strategy for Comprehensive Profiling of Human Pancreatic Tissue Proteome. In: Methods in Molecular Biology. Vol 1788. Humana Press Inc.; 2018:215-224. doi:10.1007/7651_2017_77
62. Park SKR, Aslanian A, Mcclatchy DB, et al. Census 2: Isobaric labeling data analysis. Bioinformatics. 2014;30(15):2208-2209. doi:10.1093/bioinformatics/btu151
63. Zecha J, Satpathy S, Kanashova T, et al. TMT labeling for the masses: A robust and cost-efficient, in-solution labeling approach. Mol Cell Proteomics. 2019;18(7):1468-1478. doi:10.1074/mcp.TIR119.001385
64. Pfammatter S, Bonneil E, Lanoix J, et al. Extending the Comprehensiveness of Immunopeptidome Analyses Using Isobaric Peptide Labeling. Anal Chem. 2020;92(13):9194-9204. doi:10.1021/acs.analchem.0c01545
65. Sturm RM, Lietz CB, Li L. Improved isobaric tandem mass tag quantification by ion mobility mass spectrometry. Rapid Commun Mass Spectrom. 2014;28(9):1051-1060. doi:10.1002/rcm.6875
66. Ramírez-Tejero JA, Martínez-Lara E, Rus A, Camacho MV, Del Moral ML, Siles E. Insight into the biological pathways underlying fibromyalgia by a proteomic approach. J Proteomics. 2018;186:47-55. doi:10.1016/j.jprot.2018.07.009
67. Han CL, Sheng YC, Wang SY, Chen YH, Kang JH. Serum proteome profiles revealed dysregulated proteins and mechanisms associated with fibromyalgia syndrome in women. Sci Rep. 2020;10(1):12347. doi:10.1038/s41598-020-69271-w
68. Bradley LA. Pathophysiology of Fibromyalgia. Am J Med. 2009;122(12 SUPPL.). doi:10.1016/j.amjmed.2009.09.008
69. van Diepen JA, Berbée JFP, Havekes LM, Rensen PCN. Interactions between inflammation and lipid metabolism: Relevance for efficacy of anti-inflammatory drugs in the treatment of atherosclerosis. Atherosclerosis. 2013;228(2):306-315. doi:10.1016/j.atherosclerosis.2013.02.028
70. Wåhlén K, Ernberg M, Kosek E, Mannerkorpi K, Gerdle B, Ghafouri B. Significant correlation between plasma proteome profile and pain intensity, sensitivity, and psychological distress in women with fibromyalgia. Sci Rep. 2020;10(1):12508. doi:10.1038/s41598-020-69422-z
71. Narberhaus F. α-Crystallin-Type Heat Shock Proteins: Socializing Minichaperones in the Context of a Multichaperone Network. Microbiol Mol Biol Rev. 2002;66(1):64-93. doi:10.1128/mmbr.66.1.64-93.2002
72. Raman B, Ban T, Sakai M, et al. αB-crystallin, a small heat-shock protein, prevents the amyloid fibril growth of an amyloid β-peptide and β2-microglobulin. Biochem J. 2005;392(3):573-581. doi:10.1042/BJ20050339
73. Olausson P, Ghafouri B, Ghafouri N, Gerdle B. Specific proteins of the trapezius muscle correlate with pain intensity and sensitivity – An explorative multivariate proteomic study of the trapezius muscle in women with chronic widespread pain. J Pain Res. 2016;9:345-356. doi:10.2147/JPR.S102275
74. Olausson P, Gerdle B, Ghafouri N, Sjöström D, Blixt E, Ghafouri B. Protein alterations in women with chronic widespread pain - An explorative proteomic study of the trapezius muscle. Sci Rep. 2015;5. doi:10.1038/srep11894
75. Yuan H, Wang T, Niu Y, Liu X, Fu L. AMP-activated protein kinase-mediated expression of heat shock protein beta 1 enhanced insulin sensitivity in the skeletal muscle. FEBS Lett. 2017;591(1):97-108. doi:10.1002/1873-3468.12516
76. Meeus M, Nijs J, Hermans L, Goubert D, Calders P. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: Peripheral and central mechanisms as therapeutic targets? Expert Opin Ther Targets. 2013;17(9):1081-1089. doi:10.1517/14728222.2013.818657
77. Cordero MD, Díaz-Parrado E, Carrión AM, et al. Is inflammation a mitochondrial dysfunction-dependent event in fibromyalgia? Antioxidants Redox Signal. 2013;18(7):800-807. doi:10.1089/ars.2012.4892
78. Ponnalagu D, Singh H. Insights Into the Role of Mitochondrial Ion Channels in Inflammatory Response. Front Physiol. 2020;11. doi:10.3389/fphys.2020.00258
79. Gerdle B, Ghafouri B, Lund E, et al. Evidence of Mitochondrial Dysfunction in Fibromyalgia: Deviating Muscle Energy Metabolism Detected Using Microdialysis and Magnetic Resonance. J Clin Med. 2020;9(11):3527. doi:10.3390/jcm9113527
2. Jiménez MM, Javier F, Bosquet S. Neurastenia y fibromialgia: el enlace entre el sistema nervioso y la cultura en entidades clínicas complejas. En-claves del Pensam. 2017;11(22):51-74.
3. Häuser W, Sarzi-Puttini P, Fitzcharles M-A. Fibromyalgia syndrome: under-, over- and misdiagnosis. Clin Exp Rheumatol. 2019;37 Suppl 1(1):90-97. http://www.ncbi.nlm.nih.gov/pubmed/30747096.
4. Perrot S. If fibromyalgia did not exist, we should have invented it. A short history of a controversial syndrome. Reumatismo. 2012;64(4):186-193. doi:10.4081/reumatismo.2012.186
5. Häuser W, Ablin J, Fitzcharles MA, et al. Fibromyalgia. Nat Rev Dis Prim. 2015;1(August):1-16. doi:10.1038/nrdp.2015.22
6. Sarzi-Puttini P, Giorgi V, Marotto D, Atzeni F. Fibromyalgia: an update on clinical characteristics, aetiopathogenesis and treatment. Nat Rev Rheumatol. 2020;16(11):645-660. doi:10.1038/s41584-020-00506-w
7. Hackshaw K V. The Search for Biomarkers in Fibromyalgia. Diagnostics. 2021;11(2):156. doi:10.3390/diagnostics11020156
8. Peláez-Ballestas I, Sanin LH, Moreno-Montoya J, et al. Epidemiology of the rheumatic diseases in Mexico. A study of 5 regions based on the COPCORD methodology. J Rheumatol Suppl. 2011;86(SUPPL. 86):3-8. doi:10.3899/jrheum.100951
9. Choy E, Perrot S, Leon T, et al. A patient survey of the impact of fibromyalgia and the journey to diagnosis. BMC Health Serv Res. 2010;10:102. doi:10.1186/1472-6963-10-102
10. Gendelman O, Amital H, Bar-On Y, et al. Time to diagnosis of fibromyalgia and factors associated with delayed diagnosis in primary care. Best Pract Res Clin Rheumatol. 2018;32(4):489-499. doi:10.1016/j.berh.2019.01.019
11. Lacasse A, Bourgault P, Choinière M. Fibromyalgia-related costs and loss of productivity: A substantial societal burden. BMC Musculoskelet Disord. 2016;17(1). doi:10.1186/s12891-016-1027-6
12. Berger A, Dukes E, Martin S, Edelsberg J, Oster G. Characteristics and healthcare costs of patients with fibromyalgia syndrome. Int J Clin Pract. 2007;61(9):1498-1508. doi:10.1111/j.1742-1241.2007.01480.x
13. Guymer EK, Littlejohn GO, Brand CK, Kwiatek RA. Fibromyalgia onset has a high impact on work ability in Australians. Intern Med J. 2016;46(9):1069-1074. doi:10.1111/imj.13135
14. Núñez-nevárez K, López-betancourt A, Cisneros-pérez V. Labor Condition and Severity of Fibromyalgia Condición Laboral y Severidad de la Fibromialgia. Rev Red Inv Sal Trab. 2021;4(6):54-59.
15. González E, Elorza J, Failde I. Fibromyalgia and psychiatric comorbidity: their effect on the quality of life patients. Actas Esp Psiquiatr. 38(5):295-300. http://www.ncbi.nlm.nih.gov/pubmed/21117004. Accessed June 1, 2021.
16. Coskun Benlidayi I. Role of inflammation in the pathogenesis and treatment of fibromyalgia. Rheumatol Int. 2019;39(5):781-791. doi:10.1007/s00296-019-04251-6
17. Banfi G, Diani M, Pigatto PD, Reali E. T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives. Int J Mol Sci. 2020;21(4):1186. doi:10.3390/ijms21041186
18. Van West D, Maes M. Neuroendocrine and immune aspects of fibromyalgia. BioDrugs. 2001;15(8):521-531. doi:10.2165/00063030-200115080-00004
19. Bote ME, Garca JJ, Hinchado MD, Ortega E. Inflammatory/stress feedback dysregulation in women with fibromyalgia. Neuroimmunomodulation. 2012;19(6):343-351. doi:10.1159/000341664
20. Kadetoff D, Lampa J, Westman M, Andersson M, Kosek E. Evidence of central inflammation in fibromyalgia - Increased cerebrospinal fluid interleukin-8 levels. J Neuroimmunol. 2012;242(1-2):33-38. doi:10.1016/j.jneuroim.2011.10.013
21. Peck MM, Maram R, Mohamed A, et al. The Influence of Pro-inflammatory Cytokines and Genetic Variants in the Development of Fibromyalgia: A Traditional Review. Cureus. September 2020. doi:10.7759/cureus.10276
22. Totsch SK, Sorge RE. Immune system involvement in specific pain conditions. Mol Pain. 2017;13. doi:10.1177/1744806917724559
23. Theoharides TC, Tsilioni I, Bawazeer M. Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome. Front Cell Neurosci. 2019;13. doi:10.3389/fncel.2019.00353
24. Fries E, Hesse J, Hellhammer J, Hellhammer DH. A new view on hypocortisolism. Psychoneuroendocrinology. 2005;30(10):1010-1016. doi:10.1016/j.psyneuen.2005.04.006
25. Tsilioni I, Russell IJ, Stewart JM, Gleason RM, Theoharides TC. Neuropeptides CRH, SP, HK-1, and inflammatory cytokines IL-6 and TNF are increased in serum of patients with fibromyalgia syndrome, implicating mast cells. J Pharmacol Exp Ther. 2016;356(3):664-672. doi:10.1124/jpet.115.230060
26. Furer V, Hazan E, Mor A, et al. Elevated Levels of Eotaxin-2 in Serum of Fibromyalgia Patients. Pain Res Manag. 2018;2018. doi:10.1155/2018/7257681
27. Rodriguez-Pintó I, Agmon-Levin N, Howard A, Shoenfeld Y. Fibromyalgia and cytokines. Immunol Lett. 2014;161(2):200-203. doi:10.1016/j.imlet.2014.01.009
28. Andrés-Rodríguez L, Borràs X, Feliu-Soler A, et al. Peripheral immune aberrations in fibromyalgia: A systematic review, meta-analysis and meta-regression. Brain Behav Immun. 2020;87:881-889. doi:10.1016/j.bbi.2019.12.020
29. Mendieta D, la Cruz-Aguilera DL De, Barrera-Villalpando MI, et al. IL-8 and IL-6 primarily mediate the inflammatory response in fibromyalgia patients. J Neuroimmunol. 2016;290:22-25. doi:10.1016/j.jneuroim.2015.11.011
30. Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci. 2012;122(4):143-159. doi:10.1042/CS20110340
31. Zhou YQ, Liu Z, Liu ZH, et al. Interleukin-6: An emerging regulator of pathological pain. JNeuroinflammation. 2016;13(1). doi:10.1186/s12974-016-0607-6
32. Nordlind K, Eriksson L, Seiger Å, Bakhiet M. Expression of interleukin-6 in human dorsal root ganglion cells. Neurosci Lett. 2000;280(2):139-142. doi:10.1016/S0304-3940(00)00772-2
33. Yan J, Melemedjian OK, Price TJ, Dussor G. Sensitization of dural afferents underlies migraine-related behavior following meningeal application of interleukin-6 (IL-6). Mol Pain. 2012;8:1-9. doi:10.1186/1744-8069-8-6
34. Cunha FQ, Lorenzetti BB, Poole S, Ferreira SH. Interleukin‐8 as a mediator of sympathetic pain. Br J Pharmacol. 1991;104(3):765-767. doi:10.1111/j.1476-5381.1991.tb12502.x
35. Duarte H, Teixeira AL, Rocha NP, Domingues RB. Increased interictal serum levels of CXCL8/IL-8 and CCL3/MIP-1α in migraine. Neurol Sci. 2015;36(2):203-208. doi:10.1007/s10072-014-1931-1
36. Sommer C, Leinders M, Üçeyler N. Inflammation in the pathophysiology of neuropathic pain. Pain. 2018;159(3):595-602. doi:10.1097/j.pain.0000000000001122
37. Sluka KA, Clauw DJ. Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience. 2016;338:114-129. doi:10.1016/j.neuroscience.2016.06.006
38. Illescas-Montes R, Costela-Ruiz VJ, Melguizo-Rodríguez L, De Luna-Bertos E, Ruiz C, Ramos-Torrecillas J. Application of Salivary Biomarkers in the Diagnosis of Fibromyalgia. Diagnostics. 2021;11(1):63. doi:10.3390/diagnostics11010063
39. Singh L, Kaur A, Bhatti MS, Bhatti R. Possible Molecular Mediators Involved and Mechanistic Insight into Fibromyalgia and Associated Co-morbidities. Neurochem Res. 2019;44(7):1517-1532. doi:10.1007/s11064-019-02805-5
40. Wallace DJ, Linker‐Israeli M, Hallegua D, Silverman S, Silver D, Weisman MH. Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study. Rheumatology. 2001;40(7):743-749. doi:10.1093/rheumatology/40.7.743
41. Pernambuco AP, Schetino LPL, Alvim CC, et al. Increased levels of il-17a in patients with fibromyalgia. Clin Exp Rheumatol. 2013;31(SUPPL.79):60-63.
42. Ebbinghaus M, Natura G, Segond Von Banchet G, et al. Interleukin-17A is involved in mechanical hyperalgesia but not in the severity of murine antigen-induced arthritis. Sci Rep. 2017;7(1). doi:10.1038/s41598-017-10509-5
43. Sun C, Zhang J, Chen L, et al. IL-17 contributed to the neuropathic pain following peripheral nerve injury by promoting astrocyte proliferation and secretion of proinflammatory cytokines. Mol Med Rep. 2017;15(1):89-96. doi:10.3892/mmr.2016.6018
44. Jones KD, Gelbart T, Whisenant TC, et al. Genome-wide expression profiling in the peripheral blood of patients with fibromyalgia. Clin Exp Rheumatol. 2016;34(2 Suppl 96):S89-98. http://www.ncbi.nlm.nih.gov/pubmed/27157394.
45. Wang T, Yin J, Miller AH, Xiao C. A systematic review of the association between fatigue and genetic polymorphisms. Brain Behav Immun. 2017;62:230-244. doi:10.1016/j.bbi.2017.01.007
46. Chae J, Ng T, Yeo HL, et al. Impact of TNF-α (rs1800629) and IL-6 (rs1800795) Polymorphisms on Cognitive Impairment in Asian Breast Cancer Patients. Spencer J, ed. PLoS One. 2016;11(10):e0164204. doi:10.1371/journal.pone.0164204
47. Aouizerat BE, Dodd M, Lee K, et al. Preliminary evidence of a genetic association between tumor necrosis factor alpha and the severity of sleep disturbance and morning fatigue. Biol Res Nurs. 2009;11(1):27-41. doi:10.1177/1099800409333871
48. Ernberg M, Christidis N, Ghafouri B, et al. Effects of 15weeks of resistance exercise on pro-inflammatory cytokine levels in the vastus lateralis muscle of patients with fibromyalgia. Arthritis Res Ther. 2016;18(1). doi:10.1186/s13075-016-1041-y
49. Zabihiyeganeh M, Vafaee Afshar S, Amini Kadijani A, et al. The effect of cognitive behavioral therapy on the circulating proinflammatory cytokines of fibromyalgia patients: A pilot controlled clinical trial. Gen Hosp Psychiatry. 2019;57:23-28. doi:10.1016/j.genhosppsych.2019.01.003
50. Ernberg M, Christidis N, Ghafouri B, et al. Plasma cytokine levels in fibromyalgia and their response to 15 weeks of progressive resistance exercise or relaxation therapy. Mediators Inflamm. 2018;2018. doi:10.1155/2018/3985154
51. Parkitny L, Younger J. Reduced pro-inflammatory cytokines after eight weeks of low-dose naltrexone for Fibromyalgia. Biomedicines. 2017;5(2). doi:10.3390/biomedicines5020016
52. Conti P, Gallenga CE, Caraffa A, Ronconi G, Kritas SK. Impact of mast cells in fibromyalgia and low-grade chronic inflammation: Can IL-37 play a role? Dermatol Ther. 2020;33(1). doi:10.1111/dth.13191
53. Mastrangelo F, Gallenga CE. Low-Grade Chronic Inflammation Mediated by Mast Cells in Fibromyalgia: Role of IL-37.; 2018. https://www.researchgate.net/publication/324772237.
54. Hader N, Rimon D, Kinarty A, Lahat N. Altered interleukin‐2 secretion in patients with primary fibromyalgia syndrome. Arthritis Rheum. 1991;34(7):866-872. doi:10.1002/art.1780340712
55. Hernanz W, Valenzuela A, Quijada J, et al. Lymphocyte subpopulations in patients with primary fibromyalgia. J Rheumatol. 1994;21(11):2122-2124. https://pubmed.ncbi.nlm.nih.gov/7869321/. Accessed June 2, 2021.
56. Sugimoto C, Konno T, Wakao R, Fujita H, Fujita H, Wakao H. Mucosal-Associated invariant T Cell Is a potential marker to distinguish fibromyalgia syndrome from arthritis. PLoS One. 2015;10(4). doi:10.1371/journal.pone.0121124
57. Kaufmann I, Eisner C, Richter P, et al. Lymphocyte subsets and the role of Th1/Th2 balance in stressed chronic pain patients. Neuroimmunomodulation. 2007;14(5):272-280. doi:10.1159/000115041
58. Littlejohn G, Guymer E. Neurogenic inflammation in fibromyalgia. Semin Immunopathol. 2018;40(3):291-300. doi:10.1007/s00281-018-0672-2
59. Hunsucker SW, Accurso FJ, Duncan MW. Proteomics in Pediatric Research and Practice. Adv Pediatr. 2007;54(1):9-28. doi:10.1016/j.yapd.2007.03.003
60. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463-466. doi:10.1097/COH.0b013e32833ed17
61. Liu CW, Zhang Q. Isobaric Labeling-Based LC-MS/MS Strategy for Comprehensive Profiling of Human Pancreatic Tissue Proteome. In: Methods in Molecular Biology. Vol 1788. Humana Press Inc.; 2018:215-224. doi:10.1007/7651_2017_77
62. Park SKR, Aslanian A, Mcclatchy DB, et al. Census 2: Isobaric labeling data analysis. Bioinformatics. 2014;30(15):2208-2209. doi:10.1093/bioinformatics/btu151
63. Zecha J, Satpathy S, Kanashova T, et al. TMT labeling for the masses: A robust and cost-efficient, in-solution labeling approach. Mol Cell Proteomics. 2019;18(7):1468-1478. doi:10.1074/mcp.TIR119.001385
64. Pfammatter S, Bonneil E, Lanoix J, et al. Extending the Comprehensiveness of Immunopeptidome Analyses Using Isobaric Peptide Labeling. Anal Chem. 2020;92(13):9194-9204. doi:10.1021/acs.analchem.0c01545
65. Sturm RM, Lietz CB, Li L. Improved isobaric tandem mass tag quantification by ion mobility mass spectrometry. Rapid Commun Mass Spectrom. 2014;28(9):1051-1060. doi:10.1002/rcm.6875
66. Ramírez-Tejero JA, Martínez-Lara E, Rus A, Camacho MV, Del Moral ML, Siles E. Insight into the biological pathways underlying fibromyalgia by a proteomic approach. J Proteomics. 2018;186:47-55. doi:10.1016/j.jprot.2018.07.009
67. Han CL, Sheng YC, Wang SY, Chen YH, Kang JH. Serum proteome profiles revealed dysregulated proteins and mechanisms associated with fibromyalgia syndrome in women. Sci Rep. 2020;10(1):12347. doi:10.1038/s41598-020-69271-w
68. Bradley LA. Pathophysiology of Fibromyalgia. Am J Med. 2009;122(12 SUPPL.). doi:10.1016/j.amjmed.2009.09.008
69. van Diepen JA, Berbée JFP, Havekes LM, Rensen PCN. Interactions between inflammation and lipid metabolism: Relevance for efficacy of anti-inflammatory drugs in the treatment of atherosclerosis. Atherosclerosis. 2013;228(2):306-315. doi:10.1016/j.atherosclerosis.2013.02.028
70. Wåhlén K, Ernberg M, Kosek E, Mannerkorpi K, Gerdle B, Ghafouri B. Significant correlation between plasma proteome profile and pain intensity, sensitivity, and psychological distress in women with fibromyalgia. Sci Rep. 2020;10(1):12508. doi:10.1038/s41598-020-69422-z
71. Narberhaus F. α-Crystallin-Type Heat Shock Proteins: Socializing Minichaperones in the Context of a Multichaperone Network. Microbiol Mol Biol Rev. 2002;66(1):64-93. doi:10.1128/mmbr.66.1.64-93.2002
72. Raman B, Ban T, Sakai M, et al. αB-crystallin, a small heat-shock protein, prevents the amyloid fibril growth of an amyloid β-peptide and β2-microglobulin. Biochem J. 2005;392(3):573-581. doi:10.1042/BJ20050339
73. Olausson P, Ghafouri B, Ghafouri N, Gerdle B. Specific proteins of the trapezius muscle correlate with pain intensity and sensitivity – An explorative multivariate proteomic study of the trapezius muscle in women with chronic widespread pain. J Pain Res. 2016;9:345-356. doi:10.2147/JPR.S102275
74. Olausson P, Gerdle B, Ghafouri N, Sjöström D, Blixt E, Ghafouri B. Protein alterations in women with chronic widespread pain - An explorative proteomic study of the trapezius muscle. Sci Rep. 2015;5. doi:10.1038/srep11894
75. Yuan H, Wang T, Niu Y, Liu X, Fu L. AMP-activated protein kinase-mediated expression of heat shock protein beta 1 enhanced insulin sensitivity in the skeletal muscle. FEBS Lett. 2017;591(1):97-108. doi:10.1002/1873-3468.12516
76. Meeus M, Nijs J, Hermans L, Goubert D, Calders P. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: Peripheral and central mechanisms as therapeutic targets? Expert Opin Ther Targets. 2013;17(9):1081-1089. doi:10.1517/14728222.2013.818657
77. Cordero MD, Díaz-Parrado E, Carrión AM, et al. Is inflammation a mitochondrial dysfunction-dependent event in fibromyalgia? Antioxidants Redox Signal. 2013;18(7):800-807. doi:10.1089/ars.2012.4892
78. Ponnalagu D, Singh H. Insights Into the Role of Mitochondrial Ion Channels in Inflammatory Response. Front Physiol. 2020;11. doi:10.3389/fphys.2020.00258
79. Gerdle B, Ghafouri B, Lund E, et al. Evidence of Mitochondrial Dysfunction in Fibromyalgia: Deviating Muscle Energy Metabolism Detected Using Microdialysis and Magnetic Resonance. J Clin Med. 2020;9(11):3527. doi:10.3390/jcm9113527