Evoked potentials after painful cutaneous electrical stimulation depict pain relief during a conditioned pain modulation

Abstract

BackgroundConditioned pain modulation (CPM) evaluates the pain modulating effect of a noxious conditioning stimulus (CS) on another noxious test stimulus (TS), mostly based solely on subjective pain ratings. We used painful cutaneous electrical stimulation (PCES) to induce TS in a novel CPM-model. Additionally, to evaluate a more objective parameter, we recorded the corresponding changes of cortical evoked potentials (PCES-EP).MethodsWe examined the CPM-effect in 17 healthy subjects in a randomized controlled cross-over design during immersion of the non-dominant hand into 10 °C or 24 °C cold water (CS). Using three custom-built concentric surface electrodes, electrical stimuli were applied on the dominant hand, inducing pain of 40–60 on NRS 0–100 (TS). At baseline, during and after CS we assessed the electrically induced pain intensity and electrically evoked potentials recorded over the central electrode (Cz).ResultsOnly in the 10 °C-condition, both pain (52.6 ± 4.4 (baseline) vs. 30.3 ± 12.5 (during CS)) and amplitudes of PCES-EP (42.1 ± 13.4 μV (baseline) vs. 28.7 ± 10.5 μV (during CS)) attenuated during CS and recovered there after (all p < 0.001). In the 10 °C-condition changes of subjective pain ratings during electrical stimulation and amplitudes of PCES-EP correlated significantly with each other (r = 0.5) and with CS pain intensity (r = 0.5).ConclusionsPCES-EPs are a quantitative measure of pain relief, as changes in the electrophysiological response are paralleled by a consistent decrease in subjective pain ratings. This novel CPM paradigm is a feasible method, which could help to evaluate the function of the endogenous pain modulation processes.Trial registrationGerman Clinical Trials Register DRKS-ID: DRKS00012779, retrospectively registered on 24 July 2017.

Distraction by a cognitive task has a higher impact on electrophysiological measures compared with conditioned pain modulation

“…With PCES as TS and cold water as CS we demonstrated a reduction of pain intensity during application of CS, which was accompanied by a signi cant decrease of PCES-EP amplitudes similar to our previous study 39 . The pain intensity of the cold water correlated with changes of PCESinduced pain; i. e. the more painful the conditioning stimulus was, the more pronounced it reduced the intensity of PCES-induced pain, though in contrast to the ndings of our pilot study 39 the results were not signi cant after correction for multiple comparisons. Also, the signi cant correlation between pain intensity of the cold water and ratios of PCES-EP amplitudes 39 was not found in the present study.…”

“…In summary, using the recently introduced novel CPM-paradigm we demonstrated that both PCES-induced pain and PCES-EP amplitudes can be reduced not only by CPM 20,39 but also during distraction by a cognitive task. While the amount of pain relief induced by CPM and distraction by a cognitive task did not differ signi cantly during both interventions, the decrease of PCES-EP amplitudes after distraction by a cognitive task was slightly more pronounce than during CPM.…”

“…For the cutaneous electrical stimulation three planar custom-built concentric electrodes were xed in a triangular formation on the radial dorsum of the right hand in a distance of 1.5 to 2 centimeters to each other. The electrodes were connected in parallel to a stimulator (Digitimer DS7A), thus, the given current intensity was proportionally distributed over all electrodes (for a detailed description see 39 ). Each electrical stimulus, applied simultaneously by all three stimulation electrodes, consisted of a train of three monopolar square waves (200 μs duration, 5 ms inter-wave interval within the triple train).…”

“…Cortical potentials evoked after painful cutaneous electrical stimulation (PCES-EPs) were recorded above Cz according to the international 10-20 system with reference to linked earlobes (A1-A2), as previously described 39 and stored for o ine analysis (Brain Amp, Brain Products, Germany; Bandwith: 1 Hz -1 kHz; digitization sampling rate: 5 kHz) (see gure 1C). Impedances were kept below 5 kΩ.…”

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

“…Using “pain inhibits pain” models, CPM is tested using a noxious conditioning stimulus (CS) to influence another painful test stimulus (TS), upon which the analgesic effect is tested (Nir & Yarnitsky, 2015; Yarnitsky, 2010). The TS is typically of short duration, milliseconds to seconds, during which the pain response is typically recorded by means of subjective pain ratings or nociceptive withdrawal reflexes (RIII reflex) elicited by painful stimuli to the sural nerve (Jurth, Rehberg, & von Dincklage, 2014) and more recently by changes of cortical evoked brain potentials (Höffken, Özgül, Enax-Krumova, Tegenthoff, & Maier, 2017). The CPM effect correspond to the CS-induced changes in these pain responses.…”