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Papers of the Week


Papers: 17 Aug 2019 - 23 Aug 2019


Human Studies, Pharmacology/Drug Development


2019 Dec


Pain


160


12

A randomized pilot study to investigate the effect of opioids on immunomarkers using gene expression profiling during surgery.

Authors

Wodehouse T, Demopolous M, Petty R, Miraki-Moud F, Belhaj A, Husband M, Fulton L, Randive N, Oksche A, Mehta V, Gribben J, Langford R
Pain. 2019 Dec; 160(12):2691-2698.
PMID: 31433352.

Abstract

Endogenous opioid peptides and exogenous opioids modulate immune function and animal and human studies have shown that some have a depressant immunomodulatory effect. This is potentially of high clinical significance for example in cancer patients and surgery.The primary objective of this pilot study was to evaluate the effect of morphine and oxycodone on immune pathways associated with immunosuppression in gynecological laparotomy patients.Gene expression was analyzed in CD4+, CD8+ and NK cells using the 3' Affymetrix microarray. Patients were randomized to receive morphine, oxycodone, or non-opioid 'control' analgesia during and after surgery. Genes demonstrating differential expression were those with a ≥±2-fold difference and p-value≤0.05 following ANOVA. Cytometric bead array and NK cell degranulation assay were used to investigate changes in serum cytokine concentration and in NK cell cytotoxicity, respectively. Forty patients had satisfactory RNA which was hybridized to gene chips. Genes were identified (Partek® Genomics Suite® 6.6) at baseline, 2 h, 6 h and 24 h and were either ≥2-fold up or down-regulated from baseline.At 2 h, a large number of genes were down-regulated with morphine but not with control analgesia or oxycodone. Statistically significant increases in IL-6 concentrations were induced by morphine only; NK cell activity was suppressed with morphine, but maintained with oxycodone and epidural analgesia.Gene expression profiles suggest that at 2 h post-incision morphine appeared to be immunosuppressive as compared to oxycodone and non-opioid control analgesia.