Test-Retest Reliability of 10 Hz Conditioning Electrical Stimulation Inducing Long-Term Potentiation (LTP)-Like Pain Amplification in Humans

Abstract

Background10 Hz conditioning electrical stimulation (CES) has been shown to induce long-term potentiation (LTP)-like pain amplification similar to traditional 100 Hz CES in healthy humans. The aim of this study was to assess the test-retest reliability and to estimate sample sizes required for future crossover and parallel study designs.MethodsThe 10 Hz paradigm (500 rectangular pulses lasting 50 s) was repeated on two separate days with one week interval in twenty volunteers. Perceptual intensities to single electrical stimulation (SES) at the conditioned skin site and to mechanical stimuli (pinprick and light stroking) in immediate vicinity to the conditioned skin site were recorded. Superficial blood flow (SBF) was assessed as indicator of neurogenic inflammation. All outcome measures were assessed with 10 min interval three times before and six times after the CES. The coefficient of variation and intra-class correlation coefficient were calculated within session and between sessions. Sample sizes were estimated for future crossover (Ncr) and parallel (Np) drug testing studies expected to detect a 30% decrease for the individual outcome measure following 10 Hz CES.ResultsPerceptual intensity ratings to light stroking (Ncr = 2, Np = 33) and pinprick stimulation (491 mN) (Ncr = 6, Np = 54) increased after CES and showed better reliability in crossover than parallel design. The SBF increased after CES, and then declined until reaching a plateau 20 minutes postCES. SBF showed acceptable reliability both in crossover and parallel designs (Ncr = 3, Np = 13). Pain ratings to SES were reliable, but with large estimated sample sizes (Ncr = 634, Np = 11310) due to the minor pain amplification.ConclusionsThe reliability of 10 Hz CES was acceptable in inducing LTP-like effects in the assessments of superficial blood flow, heterotopic mechanical hyperalgesia, and dysesthesia in terms of sample sizes for future crossover study designs.

Exploration of conditioned pain modulation effect on long‐term potentiation‐like pain amplification in humans

“…The HPT after CES was not found to decrease compared with the preconditioning assessments. This is in agreement with our previous reliability study showing that HPT even increased after 10‐Hz CES (Xia et al., ) which is also supported by the observations by Lang and colleagues (Lang et al., ). Together these observations indicate the absence of homotopic pain LTP by CES.…”

“…In this study, heterotopic pinprick hyperalgesia was induced 30 min after the CES for the 50.1 g pinprick testing in accordance with a recent reliability study (Xia et al., ). However, no significant decreased pain amplification was observed on painful pinprick stimulation.…”

“…First, a control non‐CES session was not arranged in this study as homotopic pain amplification might have been covered by habituation to SES. However, homotopic pain amplification after CES was absent when compared with a control non‐CES session (Xia et al., ) and when compared with pre‐CES values (Xia et al., ), while heterotopic pain amplification was present in both studies. Second, repositioning of the EPE most likely will involve activation of different nerve fibres despite markers being made on the forearm aiming to place the electrode at the same location every time.…”

“…The final DTh was determined by the geometric mean value of the three assessments. 10‐Hz CES (pulse duration: 1 ms) was used for induction of LTP‐like pain amplification (Xia et al., ,b). This CES process lasted 50 s and consisted of 500 rectangular 1 ms pulses.…”

“…This is manifested in patients as increased response to noxious stimuli (hyperalgesia) and pain resulting from normally innoxious tactile stimuli (allodynia) (Latremoliere and Woolf, ). As a model of injury‐induced hyperalgesia, heterotopic LTP‐like pain amplification can be induced by continuous 10‐Hz conditioning electrical stimulation (CES) or bursts of 100‐Hz CES in healthy humans (Klein et al., ; Xia et al., ,b). The afferent activity in the 10‐Hz LTP model may resemble the low frequency discharging of C‐fibre nociceptors following an injury.…”