{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T02:41:42Z","timestamp":1777430502566,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>Gene expression networks associated with placebo effects are understudied; in this study, we identified transcriptomic profiles associated with placebo responsivity. Participants suffering from chronic pain underwent a verbal suggestion and conditioning paradigm with individually tailored thermal painful stimulations to elicit conditioned placebo effects. Participants reported pain intensity on a visual analog scale (VAS) anchored from zero\u2009=\u2009no pain to 100\u2009=\u2009maximum imaginable pain. RNA was extracted from venous blood and RNA sequencing and validation tests were performed to identify differentially expressed genes (DEGs) associated with placebo effects, controlling for sex and level of pain. Unbiased enrichment analyses were performed to identify biological processes associated with placebo effects. Of the 10,700 protein\u2010coding genes that passed quality control filters, 667 were found to be associated with placebo effects (FDR &lt;0.05). Most genes (97%) upregulated were associated with larger placebo effects. The 17 top transcriptome\u2010wide significant genes were further validated via RT\u2010qPCR in an independent cohort of chronic pain participants. Six of them (<jats:italic>CCDC85B<\/jats:italic>, <jats:italic>FBXL15<\/jats:italic>, <jats:italic>HAGH<\/jats:italic>, <jats:italic>PI3<\/jats:italic>, <jats:italic>SELENOM<\/jats:italic>, and <jats:italic>TNFRSF4<\/jats:italic>) showed positive and significant (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) correlation with placebo effects in the cohort. The overall DEGs were highly enriched in regulation of expression of SLITs and ROBOs (R\u2010HSA\u20109010553, FDR\u2009=\u20091.26e\u221233), metabolism of RNA (R\u2010HSA\u20108953854, FDR\u2009=\u20091.34e\u221230), Huntington's disease (hsa05016, FDR\u2009=\u20099.84e\u221231), and ribosome biogenesis (GO:0042254, FDR\u2009=\u20092.67e\u221215); alternations in these pathways might jeopardize the proneness to elicit placebo effects. Future studies are needed to replicate this finding and better understand the unique molecular dynamics of people who are more or less affected by pain and placebo.<\/jats:p>","DOI":"10.1002\/cpt.3286","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T05:05:06Z","timestamp":1715058306000},"page":"380-389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptomic Profiles Associated with Experimental Placebo Effects in Chronic Pain"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6503-4709","authenticated-orcid":false,"given":"Luana","family":"Colloca","sequence":"first","affiliation":[{"name":"Department of Pain and Translational Symptom Science, School of Nursing University of Maryland  Baltimore Maryland USA"},{"name":"Department of Anesthesiology and Psychiatry, School of Medicine University of Maryland  Baltimore Maryland USA"},{"name":"Center to Advance Chronic Pain Research University of Maryland  Baltimore Maryland USA"},{"name":"Placebo Beyond Opinions Center, School of Nursing University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7101-9556","authenticated-orcid":false,"given":"Evelina","family":"Mocci","sequence":"additional","affiliation":[{"name":"Department of Pain and Translational Symptom Science, School of Nursing University of Maryland  Baltimore Maryland USA"},{"name":"Center to Advance Chronic Pain Research University of Maryland  Baltimore Maryland USA"},{"name":"Placebo Beyond Opinions Center, School of Nursing University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6630-8425","authenticated-orcid":false,"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pain and Translational Symptom Science, School of Nursing University of Maryland  Baltimore Maryland USA"},{"name":"Center to Advance Chronic Pain Research University of Maryland  Baltimore Maryland USA"},{"name":"Placebo Beyond Opinions Center, School of Nursing University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1963-1812","authenticated-orcid":false,"given":"Rachel","family":"Massalee","sequence":"additional","affiliation":[{"name":"Department of Pain and Translational Symptom Science, School of Nursing University of Maryland  Baltimore Maryland USA"},{"name":"Placebo Beyond Opinions Center, School of Nursing University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7990-4947","authenticated-orcid":false,"given":"Shuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pain and Translational Symptom Science, School of Nursing University of Maryland  Baltimore Maryland USA"},{"name":"Placebo Beyond Opinions Center, School of Nursing University of Maryland  Baltimore Maryland USA"},{"name":"Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health School of Medicine, University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-2879","authenticated-orcid":false,"given":"Jewel","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pain and Translational Symptom Science, School of Nursing University of Maryland  Baltimore Maryland USA"},{"name":"Placebo Beyond Opinions Center, School of Nursing University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4179-8640","authenticated-orcid":false,"given":"Kesha","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pain and Translational Symptom Science, School of Nursing University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8392-8044","authenticated-orcid":false,"given":"Gloria M.","family":"Patron Fidalgo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1273-7507","authenticated-orcid":false,"given":"Gerald M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1724-5405","authenticated-orcid":false,"given":"David","family":"Goldman","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics National Institute on Alcohol Abuse and Alcoholism (NIAAA), NIH  Rockville Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7648-1312","authenticated-orcid":false,"given":"Susan G.","family":"Dorsey","sequence":"additional","affiliation":[{"name":"Department of Pain and Translational Symptom Science, School of Nursing University of Maryland  Baltimore Maryland USA"},{"name":"Department of Anesthesiology and Psychiatry, School of Medicine University of Maryland  Baltimore Maryland USA"},{"name":"Center to Advance Chronic Pain Research University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39524.439618.25"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.09.036"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000501385"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006175"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002570"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000507400"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2012.02.004"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2015.02.009"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504942200"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048135"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22496"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001370"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.124"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001578"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30360"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2016.06.002"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.11607\/jop.1151"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.12.004"},{"key":"e_1_2_10_19_1","first-page":"219","article-title":"The jaw functional limitation scale: development, reliability, and validity of 8\u2010item and 20\u2010item versions","volume":"22","author":"Ohrbach R.","year":"2008","journal-title":"J. Orofac. Pain"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0722.2008.00560.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(92)90154-4"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.39.11.1071"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.09.018"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_10_25_1","volume-title":"FastQC: A Quality Control Tool for High Throughput Sequence Data","author":"Andrews S.","year":"2010"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2013.00863"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl633"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c07491"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2015.09.003"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.035600"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-022-03008-1"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210801"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-210538"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpm-2016-0139"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.31877"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.03.014"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.114306"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216539"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13027"},{"key":"e_1_2_10_48_1","first-page":"S89","article-title":"Genome\u2010wide expression profiling in the peripheral blood of patients with fibromyalgia","volume":"34","author":"Jones K.D.","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13223-019-0382-x"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-96"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.3286","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,28]],"date-time":"2024-09-28T08:13:02Z","timestamp":1727511182000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.3286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,6]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/cpt.3286"],"URL":"https:\/\/doi.org\/10.1002\/cpt.3286","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,6]]},"assertion":[{"value":"2023-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}