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Published on: July 4, 2018
Assessment of nociceptin/orphanin FQ and micro-opioid receptor mRNA in the human right atrium
J McDonald1, A D Leonard, A Serrano-Gomez
1Department of Cardiovascular Sciences (Pharmacology and Therapeutics Group), Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Leicester Royal Infirmary, Leicester, UK.
Background:
The expression of micro (mu: MOP) and nociceptin/orphanin FQ (NOP) receptors in the human myocardium is controversial. In this polymerase chain reaction (PCR)-based study using human right atrial biopsies, we have (i) probed for mRNA encoding NOP receptor and its endogenous peptide precursor, ppN/OFQ, and mRNA encoding MOP and (ii) attempted to correlate expression with cardiac function.
Methods:
mRNA encoding MOP, NOP, and the precursor for NOP (ppN/OFQ) was assessed by quantitative real-time PCR (Q-PCR) using validated TaqMan primers and compared with a housekeeper (glyceraldehyde-3-phosphate dehydrogenase, GAPDH). Q-PCR data are expressed as the difference in cycle threshold (DeltaC(t)=C(tGene of interest)-C(tGAPDH): high value, low expression) and patients were grouped according to left ventricular ejection fraction (LVEF).
Results:
Forty patients were recruited; NOP, MOP, and ppN/OFQ mRNA were measured in 38, 29, and 10 patients, respectively. DeltaC(t) (median and range) values for NOP and MOP were 10.9 (7.8-13.7) and 16.0 (12.3-18.9), respectively, representing low expression of MOP and approximately 34-fold more NOP. MOP mRNA was not detected in seven samples and with DeltaC(t) values of approximately 20, ppN/OFQ was considered absent. When patients were grouped into normal (>50%) and impaired (<50%) LVEF, there was no difference between the groups for either NOP or MOP. In some patients, intraoperative LVEF was estimated using transoesophageal echocardiography, and there was no correlation with either NOP or MOP.
Conclusions:
The human right atrium of patients with coronary artery disease and heart failure expresses mRNA encoding NOP and possibly low levels of MOP. This does not correlate with degree of cardiac dysfunction. In addition, the atrium does not express ppN/OFQ mRNA.
Insights
The human right atrium expresses mRNA for nociceptin/orphanin FQ (NOP) receptors and low levels of micro (mu: MOP) opioid receptors. Receptor expression did not correlate with cardiac function in patients with heart failure.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- The presence of micro (mu: MOP) and nociceptin/orphanin FQ (NOP) receptors in the human myocardium is debated.
- This study investigated the expression of these receptors and their precursor in human atrial tissue.
Purpose of the Study:
- To determine the expression of NOP and MOP receptor mRNA in the human right atrium.
- To investigate the presence of mRNA for the NOP precursor peptide, ppN/OFQ.
- To correlate receptor expression with cardiac function, specifically left ventricular ejection fraction (LVEF).
Main Methods:
- Quantitative real-time PCR (Q-PCR) was used to measure mRNA levels of NOP, MOP, and ppN/OFQ in human right atrial biopsies.
- Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) served as the housekeeper gene for normalization.
- Patients were categorized based on LVEF (normal >50% vs. impaired <50%) to assess correlations.
Main Results:
- NOP receptor mRNA was detected in 38 out of 40 patients, with significantly higher expression than MOP receptor mRNA (detected in 29 patients).
- ppN/OFQ mRNA was detected in only 10 patients, indicating its absence or very low levels.
- No significant difference in NOP or MOP mRNA expression was observed between patients with normal and impaired LVEF, nor was there a correlation with intraoperative LVEF estimates.
Conclusions:
- The human right atrium expresses mRNA for NOP receptors and potentially low levels of MOP receptors.
- The expression of these receptors in the atrium does not appear to be linked to the degree of cardiac dysfunction.
- ppN/OFQ mRNA was not found to be expressed in the human atrium.
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