We recorded evoked potentials (EPs) induced by conventional transcutaneous electrical stimulation (TS), laser stimulation (LS) and epidermal electrical stimulation (ES) using a specially made needle electrode. We evaluated the activated fibers by epidermal stimulation by assessing the conduction velocity (CV) of the peripheral nerves. The EPs were recorded from Cz electrode (vertex) of the International 10-20 system in 12 healthy subjects. For the ES, the tip of a stainless steel needle electrode was inserted in the epidermis of the skin (0.2 mm in depth). Distal and proximal sites of the upper limb were stimulated by the LS and ES with an intensity which induced a definite pain sensation. Similar sites were stimulated by TS with an intensity of two times the sensory threshold. A major EP positive response (P1) was obtained by stimulation by all three types of stimuli. The P1 latency for the TS (245+/-22 ms) was significantly shorter than that for the ES (302+/-17 ms, P<0.0001) and LS (341+/-21 ms, P<0.0001) and the peak latency P1 by the LS was also significantly longer, approximately 40 ms, than that by the ES (P<0.0001). The CVs were 15.1, 15.3 and 44.1 m/s obtained by ES, LS and TS, respectively. The CV indicated that the fibers activated by the ES were mainly A fibers, which corresponded to the fibers stimulated by the LS. We considered that the ES with our newly developed needle electrode was a very convenient method for the selective stimulation of the A fibers, since it was very simple, not requiring any special apparatus, did not cause bleeding or burns and caused minimum uncomfortable feeling.

Although numerous anatomical and electrophysiological findings in animal studies have supported a hierarchical scheme of somatosensory processing, precise activation timings of each cortical area are not known. Therefore we examined the temporal relationship of activities among multiple cortical areas using magnetoencephalography in humans. We found activations in Brodmann’s areas 3b, 4, 1, 5 and the secondary somatosensory cortex region in the right hemisphere following transcutaneous electrical stimulation of the dorsum of the left hand. The mean onset latencies of each cortical activity were 14.4, 14.5, 18.0, 22.4 and 21.7 ms, respectively. The differences of onset latencies among these activations indicated the serial mode of processing both through the postcentral gyrus and through the primary and secondary somatosensory cortices.

The mechanisms by which vibrotactile stimuli relieve pain are not well understood, especially in humans. We recorded cortical magnetic responses to paired noxious (intra-epidermal electrical stimulation, IES) and innocuous (transcutaneous electrical stimulation, TS) stimuli applied to the back at a conditioning–test interval (CTI) of −500 to 500 ms. Results showed that IES-induced responses were remarkably attenuated when TS was applied 20–60 ms later and 0–500 ms earlier than IES (CTI = −60 to 500 ms). Since the signals evoked by IES reached the spinal cord (CTI = −60 to −20 ms conditions) and the cortex (−60 and −40 ms condition) earlier than those evoked by TS, the present results indicate that cortical responses to noxious stimuli can be inhibited by innocuous tactile stimuli at the cortical level, with minimal contribution at the spinal level.

The choice of a system specific stimulus is difficult when investigating the human nociceptive system, in contrast with the tactile, auditory and visual systems, because it should be noxious but not actually damage the tissue. The discomfort accompanying system specific stimulation must be kept to a minimum for ethical reasons. In this review, recent progress made in the study of human pain perception using intraepidermal electrical stimulation (IES) is described. Also, whether IES is a viable alternative to laser stimulation is discussed. IES selectively activates Aδ nociceptors, elicits a sharp pricking sensation with minimal discomfort and evokes cortical responses almost identical to those produced by laser stimulation. As IES does not require expensive equipment, and is easy to control, it would seem useful for pain research as well as clinical tests.

Although anatomical, histochemical and electrophysiological findings in both animals and humans have suggested a parallel and serial mode of auditory processing, precise activation timings of each cortical area are not well known, especially in humans. We investigated the timing of arrival of signals to multiple cortical areas using magnetoencephalography in humans. Following click stimuli applied to the left ear, activations were found in six cortical areas in the right hemisphere: the posteromedial part of Heschl's gyrus (HG) corresponding to the primary auditory cortex (PAC), the anterolateral part of the HG region on or posterior to the transverse sulcus, the posterior parietal cortex (PPC), posterior and anterior parts of the superior temporal gyrus (STG), and the planum temporale (PT). The mean onset latencies of each cortical activity were 17.1, 21.2, 25.3, 26.2, 30.9 and 47.6 ms respectively. These results suggested a serial model of auditory processing along the medio-lateral axis of the supratemporal plane and, in addition, implied the existence of several parallel streams running postero-superiorly (from the PAC to the belt region and then to the posterior STG, PPC or PT) and anteriorly (PAC–belt–anterior STG).