Acupuncture anesthesia

Detail information

ENOM00088

Accession

GSE120596

Status

Public on Apr 02, 2019

Title

Variability in the Analgesic Response to Ibuprofen Following Third Molar Extraction is Associated with Differences in Activation of the Cyclooxygenase Pathway

Organism

Homo sapiens

Experiment type

Expression profiling by high throughput sequencing

Summary

It has long been recognized that there is substantial inter-individual variability in the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), but the mechanisms underlying this variability are not well understood. In order to characterize the factors associated with heterogeneity in response to ibuprofen, we performed functional neuroimaging, pharmacokinetic/pharmacodynamic assessments, biochemical assays, and gene expression analysis in twenty-nine healthy subjects who underwent third molar extraction. Subjects were treated with rapid-acting ibuprofen (400 mg; N=19) or placebo (N=10) in a randomized, double-blind design. Compared to placebo, ibuprofen-treated subjects exhibited greater reduction in pain scores, alterations in CBF in brain regions associated with pain processing, and inhibition of ex vivo COX-1 and COX-2 activity and urinary prostaglandin metabolites (p<0.05). Ibuprofen-treated subjects could be stratified into partial responders (N=9, required rescue medication) and complete responders (N=10, no rescue medication). This variability in analgesic efficacy was not associated with demographic/clinical characteristics, markers of systemic inflammation, or ibuprofen pharmacokinetics. Complete responders exhibited less suppression of urinary prostaglandin metabolites and greater induction of serum tumor necrosis factor-α and interleukin 8, compared to partial responders (p<0.05). Partial responders exhibited more alterations in gene expression in peripheral blood mononuclear cells after surgery, with an enrichment in inflammatory pathways. These findings suggest that activation of the prostanoid biosynthetic pathway and regulation of the inflammatory response to surgery differs between partial and complete responders. Future studies are necessary to elucidate the molecular mechanisms underlying this variability and identify biomarkers that are predictive of ibuprofen response.

Samples

GSM ID	Sample info	Characteristics	Description
GSM3405450	1001_baseline	cell type: peripheral blood mononuclear cell subject: 1001 gender: Female timepoint: baseline library barcode: ATTACTCG-TATAGCCT drug treatment: ibuprofen sodium response group: Partial responder
GSM3405451	1001_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1001 gender: Female timepoint: post-surgery 1 library barcode: TCCGGAGA-TATAGCCT drug treatment: ibuprofen sodium response group: Partial responder
GSM3405452	1002_baseline	cell type: peripheral blood mononuclear cell subject: 1002 gender: Female timepoint: baseline library barcode: CGCTCATT-TATAGCCT drug treatment: Placebo response group: Placebo
GSM3405453	1002_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1002 gender: Female timepoint: post-surgery 1 library barcode: GAGATTCC-TATAGCCT drug treatment: Placebo response group: Placebo
GSM3405454	1003_baseline	cell type: peripheral blood mononuclear cell subject: 1003 gender: Male timepoint: baseline library barcode: ATTCAGAA-TATAGCCT drug treatment: ibuprofen sodium response group: Full responder
GSM3405455	1003_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1003 gender: Male timepoint: post-surgery 1 library barcode: GAATTCGT-TATAGCCT drug treatment: ibuprofen sodium response group: Full responder
GSM3405456	1004_baseline	cell type: peripheral blood mononuclear cell subject: 1004 gender: Male timepoint: baseline library barcode: CTGAAGCT-TATAGCCT drug treatment: ibuprofen sodium response group: Partial responder
GSM3405457	1004_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1004 gender: Male timepoint: post-surgery 1 library barcode: TAATGCGC-TATAGCCT drug treatment: ibuprofen sodium response group: Partial responder
GSM3405458	1005_baseline	cell type: peripheral blood mononuclear cell subject: 1005 gender: Male timepoint: baseline library barcode: CGGCTATG-TATAGCCT drug treatment: Placebo response group: Placebo
GSM3405459	1005_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1005 gender: Male timepoint: post-surgery 1 library barcode: TCCGCGAA-TATAGCCT drug treatment: Placebo response group: Placebo
GSM3405460	1006_baseline	cell type: peripheral blood mononuclear cell subject: 1006 gender: Male timepoint: baseline library barcode: TCTCGCGC-TATAGCCT drug treatment: ibuprofen sodium response group: Partial responder
GSM3405461	1006_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1006 gender: Male timepoint: post-surgery 1 library barcode: AGCGATAG-TATAGCCT drug treatment: ibuprofen sodium response group: Partial responder
GSM3405462	1007_baseline	cell type: peripheral blood mononuclear cell subject: 1007 gender: Male timepoint: baseline library barcode: ATTACTCG-ATAGAGGC drug treatment: ibuprofen sodium response group: Full responder
GSM3405463	1007_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1007 gender: Male timepoint: post-surgery 1 library barcode: TCCGGAGA-ATAGAGGC drug treatment: ibuprofen sodium response group: Full responder
GSM3405464	1008_baseline	cell type: peripheral blood mononuclear cell subject: 1008 gender: Male timepoint: baseline library barcode: CGCTCATT-ATAGAGGC drug treatment: Placebo response group: Placebo
GSM3405465	1008_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1008 gender: Male timepoint: post-surgery 1 library barcode: GAGATTCC-ATAGAGGC drug treatment: Placebo response group: Placebo
GSM3405466	1008_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1008 gender: Male timepoint: post-surgery 2 library barcode: ATTCAGAA-ATAGAGGC drug treatment: Placebo response group: Placebo
GSM3405467	1011_baseline	cell type: peripheral blood mononuclear cell subject: 1011 gender: Female timepoint: baseline library barcode: GAATTCGT-ATAGAGGC drug treatment: ibuprofen sodium response group: Full responder
GSM3405468	1011_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1011 gender: Female timepoint: post-surgery 1 library barcode: CTGAAGCT-ATAGAGGC drug treatment: ibuprofen sodium response group: Full responder
GSM3405469	1011_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1011 gender: Female timepoint: post-surgery 2 library barcode: TAATGCGC-ATAGAGGC drug treatment: ibuprofen sodium response group: Full responder
GSM3405470	1012_baseline	cell type: peripheral blood mononuclear cell subject: 1012 gender: Female timepoint: baseline library barcode: CGGCTATG-ATAGAGGC drug treatment: ibuprofen sodium response group: Partial responder
GSM3405471	1012_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1012 gender: Female timepoint: post-surgery 1 library barcode: TCCGCGAA-ATAGAGGC drug treatment: ibuprofen sodium response group: Partial responder
GSM3405472	1012_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1012 gender: Female timepoint: post-surgery 2 library barcode: TCTCGCGC-ATAGAGGC drug treatment: ibuprofen sodium response group: Partial responder
GSM3405473	1014_baseline	cell type: peripheral blood mononuclear cell subject: 1014 gender: Male timepoint: baseline library barcode: AGCGATAG-ATAGAGGC drug treatment: Placebo response group: Placebo
GSM3405474	1014_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1014 gender: Male timepoint: post-surgery 1 library barcode: ATTACTCG-CCTATCCT drug treatment: Placebo response group: Placebo
GSM3405475	1014_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1014 gender: Male timepoint: post-surgery 2 library barcode: TCCGGAGA-CCTATCCT drug treatment: Placebo response group: Placebo
GSM3405476	1015_baseline	cell type: peripheral blood mononuclear cell subject: 1015 gender: Male timepoint: baseline library barcode: CGCTCATT-CCTATCCT drug treatment: ibuprofen sodium response group: Full responder
GSM3405477	1015_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1015 gender: Male timepoint: post-surgery 1 library barcode: GAGATTCC-CCTATCCT drug treatment: ibuprofen sodium response group: Full responder
GSM3405478	1015_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1015 gender: Male timepoint: post-surgery 2 library barcode: ATTCAGAA-CCTATCCT drug treatment: ibuprofen sodium response group: Full responder
GSM3405479	1016_baseline	cell type: peripheral blood mononuclear cell subject: 1016 gender: Male timepoint: baseline library barcode: GAATTCGT-CCTATCCT drug treatment: ibuprofen sodium response group: Full responder
GSM3405480	1016_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1016 gender: Male timepoint: post-surgery 1 library barcode: CTGAAGCT-CCTATCCT drug treatment: ibuprofen sodium response group: Full responder
GSM3405481	1016_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1016 gender: Male timepoint: post-surgery 2 library barcode: TAATGCGC-CCTATCCT drug treatment: ibuprofen sodium response group: Full responder
GSM3405482	1017_baseline	cell type: peripheral blood mononuclear cell subject: 1017 gender: Male timepoint: baseline library barcode: CGGCTATG-CCTATCCT drug treatment: Placebo response group: Placebo
GSM3405483	1017_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1017 gender: Male timepoint: post-surgery 1 library barcode: TCCGCGAA-CCTATCCT drug treatment: Placebo response group: Placebo
GSM3405484	1017_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1017 gender: Male timepoint: post-surgery 2 library barcode: TCTCGCGC-CCTATCCT drug treatment: Placebo response group: Placebo
GSM3405485	1018_baseline	cell type: peripheral blood mononuclear cell subject: 1018 gender: Female timepoint: baseline library barcode: AGCGATAG-CCTATCCT drug treatment: ibuprofen sodium response group: Full responder
GSM3405486	1018_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1018 gender: Female timepoint: post-surgery 1 library barcode: ATTACTCG-GGCTCTGA drug treatment: ibuprofen sodium response group: Full responder
GSM3405487	1018_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1018 gender: Female timepoint: post-surgery 2 library barcode: TCCGGAGA-GGCTCTGA drug treatment: ibuprofen sodium response group: Full responder
GSM3405488	1019_baseline	cell type: peripheral blood mononuclear cell subject: 1019 gender: Male timepoint: baseline library barcode: CGCTCATT-GGCTCTGA drug treatment: ibuprofen sodium response group: Full responder
GSM3405489	1019_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1019 gender: Male timepoint: post-surgery 1 library barcode: GAGATTCC-GGCTCTGA drug treatment: ibuprofen sodium response group: Full responder
GSM3405490	1019_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1019 gender: Male timepoint: post-surgery 2 library barcode: ATTCAGAA-GGCTCTGA drug treatment: ibuprofen sodium response group: Full responder
GSM3405491	1020_baseline	cell type: peripheral blood mononuclear cell subject: 1020 gender: Female timepoint: baseline library barcode: GAATTCGT-GGCTCTGA drug treatment: Placebo response group: Placebo
GSM3405492	1020_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1020 gender: Female timepoint: post-surgery 1 library barcode: CTGAAGCT-GGCTCTGA drug treatment: Placebo response group: Placebo
GSM3405493	1020_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1020 gender: Female timepoint: post-surgery 2 library barcode: TAATGCGC-GGCTCTGA drug treatment: Placebo response group: Placebo
GSM3405494	1021_baseline	cell type: peripheral blood mononuclear cell subject: 1021 gender: Female timepoint: baseline library barcode: CGGCTATG-GGCTCTGA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405495	1021_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1021 gender: Female timepoint: post-surgery 1 library barcode: TCCGCGAA-GGCTCTGA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405496	1021_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1021 gender: Female timepoint: post-surgery 2 library barcode: TCTCGCGC-GGCTCTGA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405497	1022_baseline	cell type: peripheral blood mononuclear cell subject: 1022 gender: Male timepoint: baseline library barcode: AGCGATAG-GGCTCTGA drug treatment: ibuprofen sodium response group: Full responder
GSM3405498	1022_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1022 gender: Male timepoint: post-surgery 1 library barcode: ATTACTCG-AGGCGAAG drug treatment: ibuprofen sodium response group: Full responder
GSM3405499	1022_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1022 gender: Male timepoint: post-surgery 2 library barcode: TCCGGAGA-AGGCGAAG drug treatment: ibuprofen sodium response group: Full responder
GSM3405500	1023_baseline	cell type: peripheral blood mononuclear cell subject: 1023 gender: Male timepoint: baseline library barcode: CGCTCATT-AGGCGAAG drug treatment: Placebo response group: Placebo
GSM3405501	1023_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1023 gender: Male timepoint: post-surgery 1 library barcode: GAGATTCC-AGGCGAAG drug treatment: Placebo response group: Placebo
GSM3405502	1023_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1023 gender: Male timepoint: post-surgery 2 library barcode: ATTCAGAA-AGGCGAAG drug treatment: Placebo response group: Placebo
GSM3405503	1024_baseline	cell type: peripheral blood mononuclear cell subject: 1024 gender: Female timepoint: baseline library barcode: GAATTCGT-AGGCGAAG drug treatment: ibuprofen sodium response group: Partial responder
GSM3405504	1024_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1024 gender: Female timepoint: post-surgery 1 library barcode: CTGAAGCT-AGGCGAAG drug treatment: ibuprofen sodium response group: Partial responder
GSM3405505	1024_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1024 gender: Female timepoint: post-surgery 2 library barcode: TAATGCGC-AGGCGAAG drug treatment: ibuprofen sodium response group: Partial responder
GSM3405506	1026_baseline	cell type: peripheral blood mononuclear cell subject: 1026 gender: Female timepoint: baseline library barcode: CGGCTATG-AGGCGAAG drug treatment: Placebo response group: Placebo
GSM3405507	1026_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1026 gender: Female timepoint: post-surgery 1 library barcode: TCCGCGAA-AGGCGAAG drug treatment: Placebo response group: Placebo
GSM3405508	1026_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1026 gender: Female timepoint: post-surgery 2 library barcode: TCTCGCGC-AGGCGAAG drug treatment: Placebo response group: Placebo
GSM3405509	1027_baseline	cell type: peripheral blood mononuclear cell subject: 1027 gender: Female timepoint: baseline library barcode: AGCGATAG-AGGCGAAG drug treatment: Placebo response group: Placebo
GSM3405510	1027_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1027 gender: Female timepoint: post-surgery 1 library barcode: ATTACTCG-TAATCTTA drug treatment: Placebo response group: Placebo
GSM3405511	1027_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1027 gender: Female timepoint: post-surgery 2 library barcode: TCCGGAGA-TAATCTTA drug treatment: Placebo response group: Placebo
GSM3405512	1028_baseline	cell type: peripheral blood mononuclear cell subject: 1028 gender: Male timepoint: baseline library barcode: CGCTCATT-TAATCTTA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405513	1028_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1028 gender: Male timepoint: post-surgery 1 library barcode: GAGATTCC-TAATCTTA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405514	1028_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1028 gender: Male timepoint: post-surgery 2 library barcode: ATTCAGAA-TAATCTTA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405515	1029_baseline	cell type: peripheral blood mononuclear cell subject: 1029 gender: Male timepoint: baseline library barcode: GAATTCGT-TAATCTTA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405516	1029_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1029 gender: Male timepoint: post-surgery 1 library barcode: CTGAAGCT-TAATCTTA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405517	1029_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1029 gender: Male timepoint: post-surgery 2 library barcode: TAATGCGC-TAATCTTA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405518	1030_baseline	cell type: peripheral blood mononuclear cell subject: 1030 gender: Female timepoint: baseline library barcode: CGGCTATG-TAATCTTA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405519	1030_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1030 gender: Female timepoint: post-surgery 1 library barcode: TCCGCGAA-TAATCTTA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405520	1030_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1030 gender: Female timepoint: post-surgery 2 library barcode: TCTCGCGC-TAATCTTA drug treatment: ibuprofen sodium response group: Partial responder
GSM3405521	1032_baseline	cell type: peripheral blood mononuclear cell subject: 1032 gender: Female timepoint: baseline library barcode: AGCGATAG-TAATCTTA drug treatment: Placebo response group: Placebo
GSM3405522	1032_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1032 gender: Female timepoint: post-surgery 1 library barcode: ATTACTCG-CAGGACGT drug treatment: Placebo response group: Placebo
GSM3405523	1032_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1032 gender: Female timepoint: post-surgery 2 library barcode: TCCGGAGA-CAGGACGT drug treatment: Placebo response group: Placebo
GSM3405524	1033_baseline	cell type: peripheral blood mononuclear cell subject: 1033 gender: Male timepoint: baseline library barcode: CGCTCATT-CAGGACGT drug treatment: ibuprofen sodium response group: Full responder
GSM3405525	1033_post-surgery_1	cell type: peripheral blood mononuclear cell subject: 1033 gender: Male timepoint: post-surgery 1 library barcode: GAGATTCC-CAGGACGT drug treatment: ibuprofen sodium response group: Full responder
GSM3405526	1033_post-surgery_2	cell type: peripheral blood mononuclear cell subject: 1033 gender: Male timepoint: post-surgery 2 library barcode: ATTCAGAA-CAGGACGT drug treatment: ibuprofen sodium response group: Full responder

Platform

GPL15520: Illumina MiSeq (Homo sapiens)

Indicator

Fc receptor-mediated phagocytosis in macrophages and monocytes, TREM1 signaling , Neuroinflammation signaling pathway, CD28 signaling in T helper cells, Production of nitric oxide and reactive oxygen species in macrophages

Download

Download data in GEO database