Posttraumatic headache: pain related evoked potentials (PREP) and conditioned pain modulation (CPM) to assess the pain modulatory function.

Posttraumatic headache (PTH) is common following traumatic brain injury and impacts quality of life. We investigated descending pain modulation as one possible mechanism for PTH and correlated it to clinical measures. Pain-related evoked potentials (PREP) were recorded in 26 PTH-patients and 20 controls after electrical stimulation at the right hand and forehead with concentric surface electrodes. Conditioned pain modulation (CPM) was assessed using painful cutaneous electric stimulation (PCES) on the right hand as test stimulus and immersion of the left hand into 10 °C-cold water bath as conditioning stimulus based on changes in pain intensity and in amplitudes of PCES-evoked potentials. All participants completed questionnaires assessing depression, anxiety, and pain catastrophising. PTH-patients reported significantly higher pain ratings during PREP-recording in both areas despite similar stimulus intensity at pain threshold. N1P1-amplitudes during PREP and CPM-assessment were lower in patients in both areas, but statistically significant only on the hand. Both, PREP-N1-latencies and CPM-effects (based on the N1P1-amplitudes and pain ratings) were similar in both groups. Patients showed significantly higher ratings for anxiety and depression, which did not correlate with the CPM-effect. Our results indicate generalized hyperalgesia for electrical stimuli in both hand and face in PTH. The lacking correlation between pain ratings and EEG parameters indicates different mechanisms of pain perception and nociception.

Anodal transcutaneous spinal direct current stimulation influences the amplitude of pain-related evoked potentials in healthy subjects.

It has already been described that transcutaneous spinal direct current stimulation (tsDCS) can selectively influence nociceptive evoked potentials. This study is the first aiming to prove an influence of tsDCS on pain-related evoked potentials (PREP) using concentric surface electrodes (CE), whose nociceptive specificity is still under discussion. 28 healthy subjects participated in this sham-controlled, double-blind cross-over study. All subjects underwent one session of anodal and one session of sham low-thoracic tsDCS. Before and after the intervention, PREP using CE, PREP-induced pain perception and somatosensory evoked potentials (SEP) were assessed on the right upper and lower limb. We found a decrease in PREP amplitude at the lower limb after sham stimulation, but not after anodal tsDCS, while SEP remained unchanged under all studied conditions. There was no difference between the effects of anodal tsDCS and sham stimulation on the studied parameters assessed at the upper limb. PREP-induced pain of the upper and lower limb increased after anodal tsDCS. The ability of influencing PREP using a CE at the spinal level in contrast to SEP suggests that PREP using CE follows the spinothalamic pathway and supports the assumption that it is specifically nociceptive. However, while mainly inhibitory effects on nociceptive stimuli have already been described, our results rather suggest that anodal tsDCS has a sensitizing effect. This may indicate that the mechanisms underlying the elicitation of PREP with CE are not the same as for the other nociceptive evoked potentials. The effects on the processing of different types of painful stimuli should be directly compared in future studies.

Pain-related evoked potentials with concentric surface electrodes in patients and healthy subjects: a systematic review.

Pain-related evoked potentials with concentric surface electrodes (PREP with CE) have been increasingly used in the diagnostics of polyneuropathies as well as in pain research. However, the study results are partly inconsistent regarding their utility to distinguish between normal and abnormal findings. The present systematic review aimed to summarise and compare study results, where PREP with CE were used in healthy subjects or patients and to identify possible influencing factors. We found 36 research articles, of which 21 investigated disorders in patients compared to healthy controls, while the other 15 focussed on basic research in healthy subjects. Patients with polyneuropathies showed the most consistent PREP results with similar prolonged latencies and reduced amplitude values. Findings in other patient groups or in healthy subjects were more heterogeneous. There was evidence for an influence by age and height as well as by central effects like emotions, which should be considered in further studies. Further systematic research analysing PREP results depending on individual and disease-specific factors is needed to develop optimal normative values.

Bilaterally prolonged latencies of pain-related evoked potentials in peripheral nerve injuries.

OBJECTIVE: Cross-sectional study to test the applicability of pain-related evoked potentials (PREP) for the diagnosis of peripheral nerve injuries (PNI). INTRODUCTION: Patients with generalized polyneuropathies show prolonged latencies and decreased amplitudes of PREP indicating an impairment of A-delta fibers. Although these fibers are frequently affected in PNI, it is unclear, if PREP-testing detects PNI comparable to Nerve Conduction Studies (NCS). METHODS: 23 patients with PNI of one upper limb underwent bilateral PREP-testing (using concentric surface electrodes) and NCS. 41 healthy controls underwent PREP-testing only. We determined pain thresholds, N1-latencies and N1P1-amplitudes of PREP and analyzed them for group and side-to-side differences. Small-fiber function was evaluated using thermal detection thresholds of Quantitative Sensory Testing (QST). N1-latencies above a cut-off calculated by ROC-analysis were defined as abnormal in order to compare detection rates of PREP and NCS. RESULTS: Patients with PNI showed bilaterally prolonged N1-latencies (ipsilateral: 167.0 ±â€¯40.7 ms vs. 141.2 ±â€¯20.5 ms / contralateral: 160.0 ±â€¯41.0 ms vs. 140.2 ±â€¯23.9 ms) without a significant side-to-side difference. Pain thresholds were increased on the affected side only (4.6 ±â€¯5.2 mA vs. 2.4 ±â€¯1.4 mA (controls)). N1P1-amplitudes did not differ between patients and controls. 7 (32%) patients showed prolonged N1-latencies (>176 ms) of PREP. NCS were abnormal in 16 (73%) cases. 13 (59%) patients showed thermal hypoesthesia in QST. CONCLUSION: Contrary to our expectations, we found bilaterally prolonged N1-latencies and normal N1P1-amplitudes in patients with PNI. Our findings support the hypothesis of a bilateral generation of PREP and indicate that PREP are not suitable for the diagnosis of PNI.

High test-retest-reliability of pain-related evoked potentials (PREP) in healthy subjects.

Pain-related evoked potentials (PREP) is an established electrophysiological method to evaluate the signal transmission of electrically stimulated A-delta fibres. Although prerequisite for its clinical use, test-retest-reliability and side-to-side differences of bilateral stimulation in healthy subjects have not been examined yet. We performed PREP twice within 3-14days in 33 healthy subjects bilaterally by stimulating the dorsal hand. Detection (DT) and pain thresholds (PT) after electrical stimulation, the corresponding pain ratings, latencies of P0, N1, P1 and N2 components and the corresponding amplitudes were assessed. Impact of electrically induced pain intensity, age, sex, and arm length on PREP was analysed. MANOVA, t-Test, interclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Bland-Altmann-Analysis as well as ANCOVA were used for statistical analysis. Measurement from both sides on both days resulted in mean N1-latencies from 142.39±18.12ms to 144.03±16.62ms and in mean N1P1-amplitudes from 39.04±12.26µV to 40.53±12.9µV. Analysis of a side-to-side effect showed for the N1-latency a F-value of 0.038 and for the N1P1-amplitude of 0.004 (p>0.8). We found intraclass correlation coefficients (ICC) from 0.88 to 0.93 and a standard error of measurement (SEM)<10% of mean values for all measurements concerning the N1-Latency and N1P1-amplitude. Intraclass correlation coefficients, standard error of measurement and Bland-Altman-Analyses revealed excellent test-retest-reliability for N1-latency and N1P1-amplitude without systematic error and there was no side-to-side effect on PREP. N1-latency (r=0.35, p<0.05) and N1P1-amplitude (r=-0.45, p<0.05) correlated with age and additionally N1-latency correlated with arm length (r=0.45, p<0.001). In contrast, pain intensity during the stimulation had no effect on both N1-latency and N1P1-amplitude. In summary, PREP showed high test-retest-reliability and negligible side-to-side differences concerning the commonly used parameters N1-latency and N1P1-amplitude.