Abstract
Animal studies have shown that high-frequency stimulation (HFS) of peripheral C-fibres induces long-term potentiation (LTP) within spinal nociceptive pathways. The aim of this replication study was to assess if a perceptual correlate of LTP can be observed in humans. In 20 healthy volunteers, we applied HFS to the left or right volar forearm. Before and after applying HFS, we delivered single electrical test stimuli through the HFS electrode while a second electrode at the contra-lateral arm served as a control condition. Moreover, to test the efficacy of the HFS protocol, we quantified changes in mechanical pinprick sensitivity before and after HFS of the skin surrounding both electrodes. The perceived intensity was collected for both electrical and mechanical stimuli. After HFS, the perceived pain intensity elicited by the mechanical pinprick stimuli applied on the skin surrounding the HFS-treated site was significantly higher compared to control site (heterotopic effect). Furthermore, we found a higher perceived pain intensity for single electrical stimuli delivered to the HFS-treated site compared to the control site (homotopic effect). Whether the homotopic effect reflects a perceptual correlate of homosynaptic LTP remains to be elucidated.
Highlights
Animal studies have shown that high-frequency electrical stimulation (HFS) of the sciatic nerve of rats induces homosynaptic long-term potentiation (LTP) between peripheral C-fibres and lamina I spinal neurons projecting to the brain [1,2]
Since our aim was to replicate the homotopic effect of high-frequency stimulation (HFS), we reduced the number of tests for the heterotopic effects as compared to the study of Klein et al we only tested mechanical pinprick sensitivity at baseline, before applying the electrical test stimuli, and at 60 min after applying HFS, after the last electrical test stimulus
Primary outcome: perceived pain intensity elicited by single electrical stimuli after high-frequency stimulation
Summary
Animal studies have shown that high-frequency electrical stimulation (HFS) of the sciatic nerve of rats induces homosynaptic long-term potentiation (LTP) between peripheral C-fibres and lamina I spinal neurons projecting to the brain [1,2] This finding has led to the idea that LTP within spinal nociceptive pathways could be one of the processes underlying long-lasting hyperalgesia. In a first attempt to provide translational evidence for the role of LTP in hyperalgesia, Klein et al [3] applied HFS to the human skin using an electrode designed to preferentially activate skin nociceptors They found that the painful percept elicited by single electrical test stimuli delivered through the HFS electrode was enhanced for at least 60 min (further referred to as homotopic effect) after applying HFS. The authors suggested that at least part of the homotopic effect reflects a perceptual correlate of homosynaptic LTP, whereas the heterotopic effects represent a perceptual correlate of heterosynaptic LTP [3]
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