The effect of HFS-induced central sensitization on resting state EEG

Background and aims Previous studies have shown that High Frequency electrical Stimulation (HFS) of skin nociceptors can produce an increase in sensitivity to mechanical pinprick stimuli attributed to long-term potentation within spinal nociceptive pathway and, possibly, increased excitability within supra spinal relays leading to the primary somatosensory cortex S1. Here, we aimed at characterizing the relationship between HFS-induced secondary hyperalgesia and changes in brain activity at rest. To do so, we compared the frequency content of resting state EEG before and after HFS. The analyses focused on the signals measured over S1, as previously hypothesized to witness central sensitization phenomenon within resting state EEG. Methods HFS was delivered to the right volar forearm of 32 healthy participants. The electrode consisted of 10 blunt tungsten pins with a diameter of 0.25 mm protruding 0.65 mm from the base (MRC Systems). The stimulation consisted of five 100 Hz trains of square-wave pulses delivered every 10 seconds during one second. Sensitivity to pinprick stimulation (128 mN) was evaluated before and 30 minutes after HFS using a Numerical Rating Scale (NRS) ranging from 0 (no perception) to 100 (most intense imaginable pain) with 50 as the anchor between non-painful and painful sensation. We used the average of 3 successive ratings for statistical analysis. Resting state EEG (60 sec eyes closed to enhance alpha-band amplitude, 64 channels, 1 kHz sampling rate) was recorded before and 30 minutes after HFS. The spectral content was analyzed offline using a Fast Fourier Transform (FFT) on halfoverlapping 5 seconds segments. The amplitude of four different frequency bands were analyzed after averaging the signal from the left and right central electrodes C3-C4 : delta (0–4 Hz), theta (4-8 Hz, alpha (8–12 Hz) and beta (12-30 Hz). One tailed paired-sample t-tests were used to assess differences in the maximum amplitude within these frequency bands before versus after HFS. A Pearson’s correlation was used to evaluate whether these differences were correlated with the changes in pinprick sensitivity. Results One subject was excluded because he failed to develop an area of increased sensitivity to pinprick stimuli after HFS. After HFS, pinprick ratings were significantly increased at the sensitized forearm and significantly decreased at the contralateral forearm (both p<.001). A significant increase in alpha-band amplitude (p=0.015) and a marginal decrease in delta-band amplitude (p=0.033) was observed. There was no significant correlation between the post-HFS change in delta, theta, alpha or beta amplitude and the post-HFS increase in pinprick ratings at the sensitized forearm. In contrast, there was a positive correlation between the change in pinprick sensitivity at the control arm and the change in alpha-band (r(29)=0.412, p=0.021) and beta-band (r(29)=0.519, p=0.003) amplitudes. Conclusion HFS applied to the volar forearm is associated with a decrease in delta band activity and an increase in alpha band activity, possibly explained by changes in the level of vigilance. These post-HFS changes in EEG activity were not correlated with the HFS-induced increase in pinprick sensitivity at the sensitized forearm. We also observed a positive correlation between the the changes in amplitude of alpha- and beta-band amplitudes and the reduced sensitivity to pinprick stimuli at the control arm, possibly due to some form of habituation