Abstract

High frequency electrical stimulation (HFS) of the skin induces increased pinprick sensitivity in the surrounding unconditioned skin (secondary hyperalgesia). Moreover, it has been shown that brief high intensity CO2 laser stimuli, activating both A{delta}- and C-fiber nociceptors, are perceived as more intense when delivered in the area of secondary hyperalgesia. To investigate the contribution of A-fiber nociceptors to secondary hyperalgesia the present study assessed if the perception and brain responses elicited by low-intensity intra-epidermal electrical stimulation (IES), a method preferentially activating A{delta}-fiber nociceptors, are increased in the area of secondary hyperalgesia. HFS was delivered to one of the two forearms of seventeen healthy volunteers. Mechanical pinprick stimulation and IES were delivered at both arms before HFS (T0), 20 minutes after HFS (T1) and 45 minutes after HFS (T2). In all participants, HFS induced an increase in pinprick perception at the HFS-treated arm, adjacent to the site of HFS. This increase was significant at both T1 and T2. HFS did not affect the percept elicited by IES, but did enhance the magnitude of the N2 wave of IES-evoked brain potentials, both at T1 and at T2. HFS induced a long-lasting enhancement of the N2 wave elicited by IES in the area of secondary hyperalgesia, indicating that HFS enhances the responsiveness of the central nervous system to nociceptive inputs conveyed by AMH-II nociceptors. However, we found no evidence that HFS affects the perception elicited by IES, which may suggest that AMH-II nociceptors do not contribute to HFS-induced secondary hyperalgesia.