Exploration of the conditioning electrical stimulation frequencies for induction of long-term potentiation-like pain amplification in humans

Abstract

Background: Spinal nociceptive long-term potentiation (LTP) can be induced by high or low frequency conditioning electrical stimulation (CES) in rodent preparations in vitro. However, there is still sparse information on the effect of different conditioning frequencies inducing LTP-like pain amplification in humans. In this study we tested two other paradigms aiming to explore the CES frequency effect inducing pain amplification in healthy humans.Methods: Cutaneous LTP-like pain amplification induced by three different paradigms (10 Hz, 100 Hz, and 200 Hz CES) was assessed in fifteen volunteers in a cross-over design. Perceptual intensity ratings to single electrical stimulation at the conditioned site and to mechanical stimuli (pinprick and light stroking) in the immediate vicinity were recorded; superficial blood flow was also measured. The short-form of the McGill Pain Questionnaire (SF-MPQ) was used for characterizing the perception induced by CES. Results:Compared with the control session, pain perception to pinprick stimuli and area of allodynia significantly increased after all three CES paradigms. In the 10 Hz and 200 Hz sessions, the superficial blood flow 10 min after CES was significantly higher than in the control session reaching a plateau after 20 min and 10 min, respectively; for the 100 Hz paradigm a stable level was found without significant differences compared with CES and control sessions. 10 Hz CES caused a lower SF-MPQ score than 100 Hz. Conclusions:High frequency (200 Hz) and low frequency (10 Hz) paradigms can induce heterotopic pain amplification similar to the traditional 100 Hz paradigm. The 10 Hz paradigm can be an appealing alternative paradigm in future studies due to its specific association with low-level discharging of C-fibers during inflammation.

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

“…In this study, 12.8 g pinprick stimulus is on the edge between non-painful light-stroking stimuli and painful pinprick stimuli; so, it may be dynamic for 12.8 g stimulus to present the decreased perception intensity amplification. In our previous study (Xia et al, 2016a), a gradual increase in pinprick pain amplification was present until reaching the plateau 30 min after CES. Therefore, the significant decrease in perception amplification could be present when the amplification reached the plateau (i.e.…”

“…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.…”

Higher-order power harmonics of pulsed electrical stimulation modulates corticospinal contribution of peripheral nerve stimulation

“…In this study, we expand on the role of waveform by introducing a novel concept: although it is known that stimulation frequency of pulses is important (when the “frequency” of stimulation is reported, this typically indicates the timing of pulses and not the signal frequency content), it is also important to consider high-order power (frequency content in harmonics across the spectrum). Indeed, these results may change our interpretation of low vs. high pulse frequency stimulation, as low-frequency with harmonics may have similar harmonic components as high-frequency stimulation3940414243. Conversely, these results may impact very high (kHz) pulse frequency stimulation where sub-harmonics may be important, noting that pulse-shapes influence harmonics4445464748.…”