Is the conditioned pain modulation paradigm reliable? A test-retest assessment using the nociceptive withdrawal reflex

José A Biurrun Manresa, Raphael Fritsche, Pascal H Vuilleumier, Carmen Oehler, Carsten D Mørch, Lars Arendt-Nielsen, Ole K Andersen, Michele Curatolo, José A Biurrun Manresa, Raphael Fritsche, Pascal H Vuilleumier, Carmen Oehler, Carsten D Mørch, Lars Arendt-Nielsen, Ole K Andersen, Michele Curatolo

Abstract

The aim of this study was to determine the reliability of the conditioned pain modulation (CPM) paradigm assessed by an objective electrophysiological method, the nociceptive withdrawal reflex (NWR), and psychophysical measures, using hypothetical sample sizes for future studies as analytical goals. Thirty-four healthy volunteers participated in two identical experimental sessions, separated by 1 to 3 weeks. In each session, the cold pressor test (CPT) was used to induce CPM, and the NWR thresholds, electrical pain detection thresholds and pain intensity ratings after suprathreshold electrical stimulation were assessed before and during CPT. CPM was consistently detected by all methods, and the electrophysiological measures did not introduce additional variation to the assessment. In particular, 99% of the trials resulted in higher NWR thresholds during CPT, with an average increase of 3.4 mA (p<0.001). Similarly, 96% of the trials resulted in higher electrical pain detection thresholds during CPT, with an average increase of 2.2 mA (p<0.001). Pain intensity ratings after suprathreshold electrical stimulation were reduced during CPT in 84% of the trials, displaying an average decrease of 1.5 points in a numeric rating scale (p<0.001). Under these experimental conditions, CPM reliability was acceptable for all assessment methods in terms of sample sizes for potential experiments. The presented results are encouraging with regards to the use of the CPM as an assessment tool in experimental and clinical pain. Trial registration: Clinical Trials.gov NCT01636440.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Time course of the experiment.
Figure 1. Time course of the experiment.
CPT: cold pressor test. NWR: nociceptive withdrawal reflex.
Figure 2. Thresholds before and after the…
Figure 2. Thresholds before and after the cold pressor test (CPT).
Nociceptive withdrawal reflex (NWR) thresholds, electrical pain detection thresholds and pain intensity ratings to suprathreshold stimulation are shown for both sessions. **: p<0.01, ***: p<0.001.
Figure 3. Magnitude of the conditioned pain…
Figure 3. Magnitude of the conditioned pain modulation effect (ΔCPM) for both sessions.
Assessment was performed with the nociceptive withdrawal reflex (NWR) thresholds, electrical pain detection thresholds and pain intensity ratings to suprathreshold stimulation.
Figure 4. Bland-Altman plots of the magnitude…
Figure 4. Bland-Altman plots of the magnitude of the conditioned pain modulation effect (ΔCPM).
Assessment was performed with the nociceptive withdrawal reflex (NWR) thresholds, electrical pain detection thresholds and pain intensity ratings to suprathreshold stimulation. The dashed line indicates the bias between sessions, whereas the dotted lines indicate the limits of agreement, calculated as ±1.96 times the standard deviation (SD) of the differences in measurements between sessions.

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