Effect of perioperative opioids on cancer-relevant circulating parameters: mu opioid receptor and TLR4 activation potential, and proteolytic profile

Xie, Nan, Matigian, Nicholas, Vithanage, Tharindu D., Gregory, Kye, Nassar, Zeyad D., Cabot, Peter J., Shaw, Paul Nicholas, Kirkpatrick, Carl Mj, Lê Cao, Kim-Anh, Sturgess, David and Parat, Marie-Odile (2018) Effect of perioperative opioids on cancer-relevant circulating parameters: mu opioid receptor and TLR4 activation potential, and proteolytic profile. Clinical Cancer Research, 24 10: 2319-2327. doi:10.1158/1078-0432.CCR-18-0172


Author Xie, Nan
Matigian, Nicholas
Vithanage, Tharindu D.
Gregory, Kye
Nassar, Zeyad D.
Cabot, Peter J.
Shaw, Paul Nicholas
Kirkpatrick, Carl Mj
Lê Cao, Kim-Anh
Sturgess, David
Parat, Marie-Odile
Title Effect of perioperative opioids on cancer-relevant circulating parameters: mu opioid receptor and TLR4 activation potential, and proteolytic profile
Journal name Clinical Cancer Research   Check publisher's open access policy
ISSN 1078-0432
1557-3265
Publication date 2018-03-06
Year available 2018
Sub-type Article (original research)
DOI 10.1158/1078-0432.CCR-18-0172
Open Access Status Not yet assessed
Volume 24
Issue 10
Start page 2319
End page 2327
Total pages 33
Place of publication Philadelphia, PA., United States
Publisher American Association for Cancer Research
Language eng
Abstract To investigate the potential interplay between opioid analgesia and tumour metastasis through modulation of μ opioid receptor (MOR), Toll-like receptor 4 (TLR4) activation, and matrix degradation potential.

Plasma samples were collected from 60 patients undergoing elective lower limb joint replacement pre-operatively and at 3, 6 and 24 h 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. Alphascreencyclic AMP (cAMP) assay and MOR-overexpressing cells were employed to quantify MOR activation. HEK-Blue™ hTLR4 were utilised to measure TLR4 activation. Circulating matrix metalloprotease (MMP) and Tissue Inhibitor of Matrix Protease (TIMP) activities were assessed by gelatin zymography and reverse zymography, respectively.

Post-operative plasma samples displayed the ability to activate MOR and to inhibit 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 neither correlated to opioid administration nor to MOR activation potential.

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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
HERDC Pre-Audit
School of Pharmacy Publications
UQ Diamantina Institute Publications
 
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Created: Wed, 14 Mar 2018, 10:06:43 EST