{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:15Z","timestamp":1790618235299,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinal pain is the leading cause of disability worldwide. Previous studies have suggested the therapeutic effects of acetyl\u2010L\u2010carnitine (ALC) and L\u2010carnitine (LC) supplementation in specific chronic pain conditions, but not others. Mendelian randomization (MR) is an analytical approach using genetic variants for estimating causal associations. This bidirectional MR study aimed to examine the potential causal associations of ALC and LC on spinal pain (forward), and vice versa (reverse).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To obtain genetic instrumental variables, we used summary statistics from large publicly available genome\u2010wide association analyses datasets, with sample sizes between 6128 and 1,028,947 participants, for ALC, LC and spinal pain. We conducted MR analyses of potential causal associations using inverse\u2010variance weighted analysis and Causal Analysis Using Summary Effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There were no statistically significant causal associations between ALC and spinal pain or LC and spinal pain in either forward or reverse directions. Results from secondary analyses were consistent with the primary analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although some prior evidence supports the effectiveness of ALC and LC supplementation in improving pain intensity in some pain conditions, results from this bidirectional MR study do not suggest causal effects of physiologic levels of ALC or LC on spinal pain, nor causal effects of spinal pain on ALC or LC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Although some prior evidence supports the effectiveness of acetyl\u2010L\u2010carnitine (ALC) and L\u2010carnitine (LC) supplementation in improving pain intensity in some pain conditions, results from this bidirectional MR study do not suggest causal effects of circulating levels of ALC or LC on spinal pain, nor vice versa.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70407","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:13:00Z","timestamp":1790615580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Associations Between Carnitine\u2010Related Metabolites and Spinal Pain: A Bidirectional Mendelian Randomization Study"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9582-7194","authenticated-orcid":false,"given":"Abby Pei\u2010Ting","family":"Chiu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine University of Washington  Seattle Washington USA"},{"name":"Clinical, Learning, Evidence, And Research (CLEAR) Center University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta","family":"Elgaeva","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences Novosibirsk State University  Novosibirsk Russia"},{"name":"Laboratory of Recombination and Segregation Analysis Institute of Cytology and Genetics  Novosibirsk Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Arendt\u2010Nielsen","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), SMI, Medical School Aalborg University  Aalborg Denmark"},{"name":"Department of Gastroenterology &amp; Hepatology, Mech\u2010Sense, Clinical Institute Aalborg University Hospital  Aalborg Denmark"},{"name":"Steno Diabetes Center North Denmark, Clinical Institute Aalborg University Hospital  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Curatolo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine University of Washington  Seattle Washington USA"},{"name":"Clinical, Learning, Evidence, And Research (CLEAR) Center University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Suri","sequence":"additional","affiliation":[{"name":"Clinical, Learning, Evidence, And Research (CLEAR) Center University of Washington  Seattle Washington USA"},{"name":"Department of Rehabilitation Medicine University of Washington  Seattle Washington USA"},{"name":"Division of Rehabilitation Care Services VA Puget Sound Health Care System  Seattle Washington USA"},{"name":"Seattle Epidemiologic Research and Information Center VA Puget Sound Health Care System  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1099800420941105"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41387\u2010018\u20100017\u20101"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201028167\u20101"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010022\u201001270\u20101"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00023210\u2010200721001\u201000005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.12.003"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/pm\/pnae129"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2008.03.021"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2011.40.2180"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601"},{"issue":"18","key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"2032S","DOI":"10.1097\/00007632-199409151-00003","article-title":"Outcome Measures for Studying Patients With Low Back Pain","volume":"19","author":"Deyo R. 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