{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:31:02Z","timestamp":1793313062014,"version":"4.5.0"},"reference-count":72,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Fibromyalgia (FM) is a disorder characterized by widespread chronic pain, significant depression, and various neural abnormalities. Recent research suggests a reciprocal exacerbation mechanism between chronic pain and depression. In patients with FM, dysregulation of tryptophan (Trp) metabolism has been identified. Trp, an essential amino acid, serves as a precursor to serotonin (5-HT), a neuromodulator that influences mood, appetite, sleep, and pain perception through the receptors 5-HT1, 5-HT2, and 5-HT3. Additionally, Trp is involved in the kynurenine pathway, a critical route in the immune response, inflammation, and production of neuroactive substances and nicotinamide adenine dinucleotide (NAD+). The activation of this pathway by pro-inflammatory cytokines, such as tumor necrosis factor \u03b1 (TNF-\u03b1) and interferon gamma (IFN-\u03b3), leads to the production of kynurenic acid (KYNA), which has neuroprotective properties, and quinolinic acid (QA), which is neurotoxic. These findings underscore the crucial balance between Trp metabolism, 5-HT, and kynurenine, where an imbalance can contribute to the dual burden of pain and depression in patients with FM. This review proposes a novel therapeutic approach for FM pain management, focusing on inhibiting QA synthesis while co-administering selective serotonin reuptake inhibitors to potentially increase KYNA levels, thus dampening pain perception and improving patient outcomes.<\/jats:p>","DOI":"10.3390\/ph17091205","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T08:04:09Z","timestamp":1726128249000},"page":"1205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Association of the Serotonin and Kynurenine Pathways as Possible Therapeutic Targets to Modulate Pain in Patients with Fibromyalgia"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4599-1253","authenticated-orcid":false,"given":"Alfonso","family":"Alfaro-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Division of Basic Neurosciences, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Mexico City 14389, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8916-0814","authenticated-orcid":false,"given":"Samuel","family":"Reyes-Long","sequence":"additional","affiliation":[{"name":"Division of Basic Neurosciences, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Mexico City 14389, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7116-5289","authenticated-orcid":false,"given":"Ernesto","family":"Roldan-Valadez","sequence":"additional","affiliation":[{"name":"Division of Basic Neurosciences, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Mexico City 14389, Mexico"},{"name":"Department of Radiology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-4410","authenticated-orcid":false,"given":"Maykel","family":"Gonz\u00e1lez-Torres","sequence":"additional","affiliation":[{"name":"Conahcyt & Biotechnology Laboratory, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Mexico City 03940, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herlinda","family":"Bonilla-Jaime","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology, Universidad Aut\u00f3noma Metropolitana Iztapalapa, Mexico City 09340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Bandala","sequence":"additional","affiliation":[{"name":"Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Avila-Luna","sequence":"additional","affiliation":[{"name":"Division of Basic Neurosciences, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Mexico City 14389, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0291-4554","authenticated-orcid":false,"given":"Antonio","family":"Bueno-Nava","sequence":"additional","affiliation":[{"name":"Division of Basic Neurosciences, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Mexico City 14389, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9638-3638","authenticated-orcid":false,"given":"Elizabeth","family":"Cabrera-Ruiz","sequence":"additional","affiliation":[{"name":"Division of Basic Neurosciences, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Mexico City 14389, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Sanchez-Aparicio","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Facultad de Medicina Veterinaria, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50090, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1909-9146","authenticated-orcid":false,"given":"Ang\u00e9lica","family":"Gonz\u00e1lez Maciel","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Tissue Morphology, Instituto Nacional de Pediatr\u00eda, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Lilia","family":"Dotor-Llerena","sequence":"additional","affiliation":[{"name":"Division of Clinic Neurosciences, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Mexico City 14389, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9410-8535","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Cortes-Altamirano","sequence":"additional","affiliation":[{"name":"Division of Basic Neurosciences, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Mexico City 14389, Mexico"},{"name":"Department of Chiropractic, Universidad Estatal del Valle de Ecatepec, Ecatepec de Morelos 55210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/ncprheum0349","article-title":"Mechanisms of disease: Genetics of fibromyalgia","volume":"2","author":"Ablin","year":"2006","journal-title":"Nat. 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