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Effect of Perioperative Opioids on Cancer-Relevant Circulating Parameters: Mu Opioid Receptor and Toll-Like Receptor 4 Activation Potential, and Proteolytic Profile
Effect of Perioperative Opioids on Cancer-Relevant Circulating Parameters: Mu Opioid Receptor and Toll-Like Receptor 4 Activation Potential, and Proteolytic Profile
- Source :
- Clinical Cancer Research. 24:2319-2327
- Publication Year :
- 2018
- Publisher :
- American Association for Cancer Research (AACR), 2018.
-
Abstract
- Purpose: The purpose of this study is to investigate the potential interplay between opioid analgesia and tumor metastasis through modulation of μ-opioid receptor (MOR), Toll-like receptor 4 (TLR4) activation, and matrix degradation potential. Experimental Design: Plasma samples were collected from 60 patients undergoing elective lower limb joint replacement preoperatively and at 3, 6, and 24 hours after surgery; pain scores were documented at the same time points. Opioid administration was recorded and converted into morphine IV equivalents. Plasma samples were also collected from 10 healthy volunteers. Alphascreen cyclic AMP assay and MOR-overexpressing cells were employed to quantify MOR activation. HEK-Blue hTLR4 were utilized to measure TLR4 activation. Circulating matrix metalloprotease and tissue inhibitor of matrix protease activities were assessed by gelatin zymography and reverse zymography, respectively. Results: Postoperative plasma samples displayed the ability to activate MOR and to inhibit lipopolysaccharide (LPS)-induced TLR4 activation. Linear mixed model analysis revealed that MOR activation had a significant effect on inhibition of LPS-induced TLR4 activation. Furthermore, TLR4 had a significant effect to explain pain scores. Postoperative samples also displayed altered circulating matrix-degrading enzymes activity potential, but this was correlated neither to opioid administration nor to MOR activation potential. Conclusions: Our results show for the first time that (i) opioids administered to surgery patients result in modulation of ligand-induced TLR4 activation and (ii) postoperative pain is associated with increased circulating TLR4 activation potential. Our study further promotes the use of MOR activation potential rather than opioid intake in clinical studies measuring opioid exposure at a given time point. Clin Cancer Res; 24(10); 2319–27. ©2018 AACR.
- Subjects :
- 0301 basic medicine
Cancer Research
Lipopolysaccharide
Receptors, Opioid, mu
Matrix metalloproteinase
Pharmacology
Perioperative Care
Metastasis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Neoplasms
medicine
Humans
Receptor
Neoplasm Staging
Pain Measurement
business.industry
Hemodynamics
Cancer Pain
medicine.disease
Analgesics, Opioid
Toll-Like Receptor 4
030104 developmental biology
Oncology
chemistry
Opioid
030220 oncology & carcinogenesis
Proteolysis
Morphine
TLR4
μ-opioid receptor
business
Biomarkers
medicine.drug
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....50690a3c3b359534c49c1e2d76d6db64
- Full Text :
- https://doi.org/10.1158/1078-0432.ccr-18-0172