{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T20:17:34Z","timestamp":1787084254851,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Oral Rehabilitation"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Studies present ambiguous findings regarding the role of tryptophan and its metabolites, kynurenine and serotonin in chronic musculoskeletal pain. This systematic review aimed to investigate the expression of tryptophan and its metabolites, serotonin and kynurenine in patients with local and generalized chronic musculoskeletal pain in comparison with pain\u2010free controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An electronic search was conducted in the databases MEDLINE, CINAHL, EMBASE, the Cochrane Central Registry of Controlled Trials (CENTRAL) and Web of Science for clinical and observational trials from the beginning of each database to 21 April 2023. Out of 6734 articles, a total of 17 studies were included; 12 studies were used in the meta\u2010analysis of serotonin, 3 regarding tryptophan and 2 studies for a narrative synthesis regarding kynurenine. Risk of bias was assessed using the quality assessment tool for observational cohort and cross\u2010sectional studies of the National Heart, Lung, and Blood Institute, while the certainty of evidence was by GRADE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All included studies showed a low risk of bias. The meta\u2010analysis showed lower blood levels of tryptophan (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001; very low quality of evidence) and higher blood levels of serotonin (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001; very low\u2010quality evidence) in patients with generalized musculoskeletal pain, when compared to pain\u2010free individuals. In local chronic musculoskeletal pain, there were higher blood levels of serotonin (\n                      <jats:italic>p<\/jats:italic>\n                      =.251; very low quality of evidence) compared to pain\u2010free individuals. Regarding kynurenine, the studies reported both higher and lower blood levels in generalized chronic musculoskeletal pain compared to pain\u2010free individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The blood levels of tryptophan and its metabolites serotonin and kynurenine seem to influence chronic musculoskeletal pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/joor.13758","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T02:38:54Z","timestamp":1716863934000},"page":"1898-1910","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The role of tryptophan and its derivatives in musculoskeletal pains: A systematic review and 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