Time course of copeptin during a model of experimental pain and hyperalgesia: A randomised volunteer crossover trial

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A reliable biomarker for quantifying pain or hyperalgesia has yet to be found. A surrogate marker of arginine vasopressin, copeptin, is elevated in a number of states of physiological and psychological stress and may have a role in quantifying pain and/or hyperalgesia.


To evaluate copeptin as a biomarker for pain or hyperalgesia developing after 120 min of sustained electrical stimulation.


Secondary analysis of a randomised, double-blinded, crossover trial.


Single, tertiary university hospital from September 2014 to January 2015.


A total of 16 healthy, opioid-naïve white men with no confounding medication or history of pain.


Copeptin and cortisol were measured five times during an established model of transdermal electrical stimulation designed to assess pain and hyperalgesia.


The primary outcome was the change in copeptin concentration after 120 min of sustained electrical stimulation. Secondary outcomes were copeptin and cortisol concentrations after a subsequent period of rest and analyses of copeptin and cortisol concentrations were made in high-dose and low-dose fentanyl groups separately.


Total copeptin concentrations were not significantly elevated after 120 min [9.15 pmol l−1 (interquartile ranges (IQR), 3.45 to 35.45 pmol l−1); P = 0.150] compared with baseline [6.15 pmol l−1 (IQR, 3.60 to 10.62 pmol l−1)]. In the high-dose fentanyl group, there was a significant increase in copeptin within individuals [P = 0.001; median, 37.9 pmol l−1 (IQR, 8.1 to 62 pmol l−1)] after 120 min, and in the low-dose fentanyl group a significant decrease in copeptin concentrations within individuals [P = 0.006; median, 4.7 pmol l−1 (IQR, 3.13 to 9.35 pmol l−1)]. No correlation between copeptin concentration and either the area under the pain curve or area under the hyperalgesia curve could be found, indicating that the observed differences may be due to other fentanyl-mediated effects.


Copeptin concentrations do not appear to be associated directly with pain and hyperalgesia. Instead, some fentanyl-mediated effect or effects appear to have greatly increased copeptin concentrations from baseline to 120 min.


Clinicaltrials.gov identifier: NCT02252458.

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