Variability in the Analgesic Response to Ibuprofen Following Third Molar Extraction is Associated with Differences in Activation of the Cyclooxygenase Pathway
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ABSTRACT:
PROVIDER: PRJNA493653 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7910430_1.fastq.gz | Fastqsanger.gz | |||
| SRR7910430_2.fastq.gz | Fastqsanger.gz | |||
| SRR7910440_1.fastq.gz | Fastqsanger.gz | |||
| SRR7910440_2.fastq.gz | Fastqsanger.gz | |||
| SRR7910450_1.fastq.gz | Fastqsanger.gz |
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Project description: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.
2019-04-02 | GSE120596 | GEO
Project description:NSAIDs (non-steroidal anti-inflammatory drugs) inhibit cyclooxygenase (COX) enzymes and prevent Alzheimer’s disease (AD) at preclinical stages in cognitively normal aging populations. We modeled NSAID prevention of memory impairment in AD model mice to identify novel targets of NSAID action. We found that the widely-used NSAID ibuprofen prevented early hippocampus-dependent memory deficits in APP-PS1 mice. We therefore analyzed gene expression in the hippocampus of these mice.
2016-06-14 | GSE67306 | GEO
Project description:NSAIDs (non-steroidal anti-inflammatory drugs) inhibit cyclooxygenase (COX) enzymes and prevent Alzheimer's disease (AD) at preclinical stages in cognitively normal aging populations. We modeled NSAID prevention of memory impairment in AD model mice to identify novel targets of NSAID action. We found that the widely-used NSAID ibuprofen prevented early hippocampus-dependent memory deficits in APP-PS1 mice. We therefore analyzed gene expression in the hippocampus of these mice. We treated male APPSwe-PS1deltaE9 mice (strain originally provided by Dr. David Borchelt and fully back-crossed to a C57BL/6J background) and their wild-type littermates with ibuprofen in chow from 3 to 6 months of age, after which we sacrificed the mice and dissected one hippocampus from each mouse for RNA isolation and microarray analysis. In each genotype-treatment group, we analyzed samples from 5 mice. Note: In our initial analysis, we found that sample GSM1644138, Hippocampus_WT_Con_rep5, was an outlier in overall gene expression. We therefore removed this sample before performing the analysis published in PMID 27190010.
2016-06-14 | E-GEOD-67306 | biostudies-arrayexpress
Project description:ObjectiveThe aim of the present study was to evaluate the analgesic efficacy of pre-emptive intravenous (iv) ibuprofen on pain during and after the mandibular third molar surgery.MethodsA total of 60 patients were included in the study. They were allocated as ibuprofen 800 mg iv+dexketoprofen 50 mg (group 1), ibuprofen 800 mg iv alone (group 2) or placebo (group 3). A local anaesthetic infiltration was administered to all patients. In all patients, haemodynamic values (mean arterial pressure (MAP) and heart rate (HR)) were recorded preoperatively, and infusions were started. State-Trait Anxiety Inventory (STAI) scale was used to assess anxiety states. Surgery started 15 min after the infusion. Haemodynamic values and pain scores with visual analogue scale (VAS) were recorded. Pain scores were recorded postoperatively at rest (VASR) and swallowing (VASS).ResultsThere was no significant difference in the preoperative STAI values between the groups (p>0.05). HR, MAP and VAS pain scores were significantly higher in group 3 than in groups 1 and 2 (p<0.05). VASR and VASS scores were significantly higher in group 3 than in group 1 in the first 4 h postoperatively (p<0.05). VASS scores were significantly higher in group 3 than in group 2 at 1-4 h postoperatively (p<0.05), but there was no difference in VASR and VASS scores at 48 h after surgery.ConclusionIbuprofen alone or in combination with dexketoprofen provided similar analgesia in the perioperative period when administered pre-emptively.
| S-EPMC6886821 | biostudies-literature
Project description:BackgroundThis study aimed to evaluate the anti-inflammatory efficacy of preemptive intravenous ibuprofen on inflammatory complications such as edema and trismus in patients undergoing impacted mandibular third molar surgery.MethodsSixty patients were included and divided into three groups (800 mg IV ibuprofen + 50 mg dexketoprofen, 800 mg IV ibuprofen, and control). In all patients, preoperative hemodynamic values were recorded before the infusions. The operation was started at 15-min post-infusion. Evaluation of edema size on the face and mouth opening (trismus) was conducted in the preoperative period, and at postoperative 48 h and 1 week.ResultsNo difference was determined among the groups in trismus and edema size in postoperative measurements (P > 0.05). There was a difference between group 2 and group 3 only in measurement value of tragus-corner of the mouth on the postoperative day 2 (P < 0.05). A difference was found between the measurement values of trismus preoperatively and at preoperative day 2, and between postoperative day 2 and 1 week in group 3 based on time (P < 0.05). In group 3, edema on the face on postoperative day 2 increased significantly compared to that in the preoperative period (P < 0.001); in addition, edema increased significantly in groups 1 and 2 in the postoperative period but was less than that in group 3 (P < 0.001).ConclusionsIn this study, intravenous ibuprofen was determined to be more effective alone or in combination in alleviating trismus and to better limit the postoperative edema.
| S-EPMC6031972 | biostudies-literature
Project description:PurposeTo evaluate time-dependent administration of ibuprofen in a lower third molar extraction model.MethodsEleven patients requiring bilateral surgical removal of lower third molars were recruited and randomized into a blinded crossover randomized controlled trial. For 3 days after surgery, the control group was prescribed ibuprofen 400 mg every 8 h. On the other hand, the experimental group received also ibuprofen 400 mg at breakfast and lunch, replacing the dinner intake with a placebo. Pain measurements (Visual Analog Scale from 0 to 10) were recorded at baseline, 24, 48, and 72 h postoperatively. Facial swelling and trismus were also measured at baseline, 24, and 72 h postoperatively.ResultsPostoperative swelling and pain perception did not show significative difference between the control and experimental groups at 24, 48, and 72 h. Trismus was significantly lower in the control group than in the experimental group at 72 h postoperatively (p = 0.008). Rescue medication consumption seemed to be comparable between groups.ConclusionEliminating night time ibuprofen might be insignificant for pain control after third molar extraction.
| S-EPMC9345738 | biostudies-literature
Project description:Ibuprofen is one of the most commonly detected pharmaceuticals in wastewater effluent; however the effects of ibuprofen on aquatic organisms are poorly understood. This study presents the transcriptome-wide response of the inland silverside, Menidia beryllina, to chronic 14 d exposures to ibuprofen.
2015-09-01 | GSE64967 | GEO
Project description:Transcriptional profiling of small intestinal explants cultured in the absence or in the presence of Ibuprofen (100 µM). Two-condition experiment, control intestinal explants vs Ibuprofen intestinal explants
2019-01-07 | GSE108369 | GEO
Project description:Ibuprofen is one of the most commonly detected pharmaceuticals in wastewater effluent; however the effects of ibuprofen on aquatic organisms are poorly understood. This study presents the transcriptome-wide response of the inland silverside, Menidia beryllina, to chronic 14 d exposures to ibuprofen. Twenty-four samples were run on twenty-four arrays, there were six replicates for each of three ibuprofen exposure concentrations and a control group.
2015-09-01 | E-GEOD-64967 | biostudies-arrayexpress
Project description:Cyclooxygenase (COX) inhibition is of concern in fish because COX inhibitors (e.g., ibuprofen) are ubiquitous in aquatic systems/fish tissues, and can disrupt synthesis of prostaglandins that modulate a variety of essential biological functions including reproduction. Transcriptomic data and publicly available high throughput toxicity data were utilized to develop putative adverse outcome pathways (AOPs) for molecular initiating event (MIE) of COX inhibition. Effects of a waterborne exposure to indomethacin (IN; 100 µg/L), ibuprofen (IB; 200 µg/L) and celecoxib (CX; 20 µg/L) on liver metabolome and ovarian gene expression (using oligonucleotide microarrays) in sexually mature fathead minnows were examined. Metabolomic profiles of IN, IB and CX were not significantly different from control or one another. Exposure to IB and CX resulted in differential expression of comparable numbers of genes (IB = 433, CX= 545). In contrast, 2558 genes were differentially expressed in IN-treated fish. Functional analyses (canonical pathway and gene set enrichment) indicated extensive effects of IN on prostaglandin synthesis pathway, oocyte meiosis and several other processes consistent with physiological roles of prostaglandins. Transcriptomic data was congruent with apical endpoint data - IN reduced plasma prostaglandin F2 alpha concentrations, and ovarian COX activity, whereas IB and CX did not. Putative AOPs pathways for COX inhibition (MIE) leading to reproductive failure (adverse outcome) via reduction of: 1) ovulation, 2) reproductive behaviors mediated by exogenous and endogenous prostaglandins, and 3) oocyte maturation were developed. Adult fathead minnow were exposed to either 100 µg/L indomethacin, 200 µg/L ibuprofen, 20 µg/L celecoxib or UV-treated Lake Superior (control) water for 96 hours. After exposure, microarray analyses were conducted using the female gonads (n=7-8 per treatment) and metabolomic analyses were conducted using the livers of all the exposed fish.
2016-01-14 | E-GEOD-72976 | biostudies-arrayexpress