Transcriptomic Profiles Associated with Experimental Placebo Effects in Chronic Pain
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 pa...
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| Veröffentlicht in: | Clinical pharmacology and therapeutics 2024-08, Vol.116 (2), p.380-389 |
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| creator | Colloca, Luana Mocci, Evelina Wang, Yang Massalee, Rachel Chen, Shuo White, Jewel Johnson, Kesha Patron Fidalgo, Gloria M. Wilson, Gerald M. Goldman, David Dorsey, Susan G. |
| description | 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 = no pain to 100 = maximum 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‐coding genes that passed quality control filters, 667 were found to be associated with placebo effects (FDR |
| doi_str_mv | 10.1002/cpt.3286 |
| format | Article |
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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 = no pain to 100 = maximum 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‐coding genes that passed quality control filters, 667 were found to be associated with placebo effects (FDR <0.05). Most genes (97%) upregulated were associated with larger placebo effects. The 17 top transcriptome‐wide significant genes were further validated via RT‐qPCR in an independent cohort of chronic pain participants. Six of them (CCDC85B, FBXL15, HAGH, PI3, SELENOM, and TNFRSF4) showed positive and significant (P < 0.05) correlation with placebo effects in the cohort. The overall DEGs were highly enriched in regulation of expression of SLITs and ROBOs (R‐HSA‐9010553, FDR = 1.26e−33), metabolism of RNA (R‐HSA‐8953854, FDR = 1.34e−30), Huntington's disease (hsa05016, FDR = 9.84e−31), and ribosome biogenesis (GO:0042254, FDR = 2.67e−15); 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.</description><identifier>ISSN: 0009-9236</identifier><identifier>ISSN: 1532-6535</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1002/cpt.3286</identifier><identifier>PMID: 38711244</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Chronic Pain - drug therapy ; Chronic Pain - genetics ; Female ; Gene Expression Profiling - methods ; Humans ; Male ; Middle Aged ; Pain Measurement - methods ; Placebo Effect ; Transcriptome</subject><ispartof>Clinical pharmacology and therapeutics, 2024-08, Vol.116 (2), p.380-389</ispartof><rights>2024 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.</rights><rights>2024 The Authors. 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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 = no pain to 100 = maximum 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‐coding genes that passed quality control filters, 667 were found to be associated with placebo effects (FDR <0.05). Most genes (97%) upregulated were associated with larger placebo effects. The 17 top transcriptome‐wide significant genes were further validated via RT‐qPCR in an independent cohort of chronic pain participants. Six of them (CCDC85B, FBXL15, HAGH, PI3, SELENOM, and TNFRSF4) showed positive and significant (P < 0.05) correlation with placebo effects in the cohort. The overall DEGs were highly enriched in regulation of expression of SLITs and ROBOs (R‐HSA‐9010553, FDR = 1.26e−33), metabolism of RNA (R‐HSA‐8953854, FDR = 1.34e−30), Huntington's disease (hsa05016, FDR = 9.84e−31), and ribosome biogenesis (GO:0042254, FDR = 2.67e−15); alternations in these pathways might jeopardize the proneness to elicit placebo effects. 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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 = no pain to 100 = maximum 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‐coding genes that passed quality control filters, 667 were found to be associated with placebo effects (FDR <0.05). Most genes (97%) upregulated were associated with larger placebo effects. The 17 top transcriptome‐wide significant genes were further validated via RT‐qPCR in an independent cohort of chronic pain participants. Six of them (CCDC85B, FBXL15, HAGH, PI3, SELENOM, and TNFRSF4) showed positive and significant (P < 0.05) correlation with placebo effects in the cohort. The overall DEGs were highly enriched in regulation of expression of SLITs and ROBOs (R‐HSA‐9010553, FDR = 1.26e−33), metabolism of RNA (R‐HSA‐8953854, FDR = 1.34e−30), Huntington's disease (hsa05016, FDR = 9.84e−31), and ribosome biogenesis (GO:0042254, FDR = 2.67e−15); alternations in these pathways might jeopardize the proneness to elicit placebo effects. 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| subjects | Adult Chronic Pain - drug therapy Chronic Pain - genetics Female Gene Expression Profiling - methods Humans Male Middle Aged Pain Measurement - methods Placebo Effect Transcriptome |
| title | Transcriptomic Profiles Associated with Experimental Placebo Effects in Chronic Pain |
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