Is the Conditioned Pain Modulation Paradigm Reliable? A Test-Retest Assessment Using the Nociceptive Withdrawal Reflex

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

Role of endogenous pain modulation in chronic pain mechanisms and treatment

“…This reliability was shown by Biurrun Manresa et al 5 for nociceptive withdrawal reflexes as test stimulus; Jurth et al 35 found good reliability for both psychophysical and electrophysiological measures of the same reflex. Less good reliability was reported by Olesen et al 68 for psychophysical measurements.…”

Reliability of Quantitative Sensory Tests in a Low Back Pain Population

“…An increase in pressure pain detection threshold immediately after cold pressure test was an indication of functioning CPM. 12 …”

“…Conditioned pain modulation was measured as the difference in pressure pain detection threshold between measurements after and before the cold pressor test (ΔCPM). 12,13 Cutaneous Single Electrical Stimulation Electrical stimulation of the sural nerve was performed through electrodes placed distal to the lateral malleolus. A 25millisecond, train-of-5, 1 millisecond, square-wave impulse (perceived as 1 stimulus), was delivered by a computer-controlled constant current stimulator (Digitimer DS7A; Neurospec, Letchworth Garden City, UK).…”

“…8,9 Although arbitrary reliability thresholds have been reported for ICC and CV, these measures have raised serious concerns. 2,12 For example, if the ICC is applied to values with a large variation, the ICC and reliability will appear higher than when applied to values with a narrower range with the same characteristics. 2,8 The CV is seriously limited by scale change sensitivity.…”

Reliable estimation of nociceptive withdrawal reflex thresholds

“…However, the electrical stimulation applied directly over the sural nerve is often associated with substantial pain and discomfort. In both healthy volunteers and pain patients, a number of subjects find the painful stimulation intolerable and the assessment cannot be completed (Banic et al, 2004;Biurrun Manresa et al, 2014b;Sterling et al, 2008). In this way, the practical applicability of the NWR-T as a clinical measure of nociceptive excitability is reduced.…”