Tuan Diep Tran

Preferential stimulation of Aδ fibers by intra-epidermal needle electrode in humans

&NA; 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&dgr; 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&dgr; fibers, since it was very simple, not requiring any special apparatus, did not cause bleeding or burns and caused minimum uncomfortable feeling.

A comparative magnetoencephalographic study of cortical activations evoked by noxious and innocuous somatosensory stimulations

We recorded somatosensory-evoked magnetic fields and potentials produced by painful intra-epidermal stimulation (ES) and non-painful transcutaneous electrical stimulation (TS) applied to the left hand in 12 healthy volunteers to compare cortical responses to noxious and innocuous somatosensory stimulations. Our results revealed that cortical processing following noxious and innocuous stimulations was strikingly similar except that the former was delayed approximately 60 ms relative to the latter, which was well explained by a difference in peripheral conduction velocity mediating noxious (Adelta fiber) and innocuous (Abeta fiber) inputs. The first cortical activity evoked by both ES and TS was in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side. The following activities were in the bilateral secondary somatosensory cortex (SII), insular cortex, cingulate cortex, anterior medial temporal area and ipsilateral SI. The source locations did not differ between the two stimulus modalities except that the dipole for insular activity following ES was located more anterior to that following TS. Both ES and TS evoked vertex potentials consisting of a negativity followed by a positivity at a latency of 202 and 304 ms, and 134 and 243 ms, respectively. The time course of the vertex potential corresponded to that of the activity of the medial temporal area. Our results suggested that cortical processing was similar between noxious and innocuous stimulation in SI and SII, but different in insular cortex. Our data also implied that activities in the amygdala/hippocampal formation represented common effects of noxious and tactile stimulations.

Pain processing within the primary somatosensory cortex in humans

To investigate the processing of noxious stimuli within the primary somatosensory cortex (SI), we recorded magnetoencephalography following noxious epidermal electrical stimulation (ES) and innocuous transcutaneous electrical stimulation (TS) applied to the dorsum of the left hand. TS activated two sources sequentially within SI: one in the posterior bank of the central sulcus and another in the crown of the postcentral gyrus, corresponding to Brodmanns areas 3b and 1, respectively. Activities from area 3b consisted of 20‐ and 30‐ms responses. Activities from area 1 consisted of three components peaking at 26, 36 and 49 ms. ES activated one source within SI whose location and orientation were similar to those of the TS‐activated area 1 source. Activities from this source consisted of three components peaking at 88, 98 and 109 ms, later by 60 ms than the corresponding TS responses. ES and TS subsequently activated a similar region in the upper bank of the sylvian fissure, corresponding to the secondary somatosensory cortex (SII). The onset latency of the SII activity following ES (109 ms) was later by 29 ms than that of the first SI response (80 ms). Likewise, the onset latency of SII activity following TS (52 ms) was later by 35 ms than that of area 1 of SI (17 ms). Therefore, our results showed that the processing of noxious and innocuous stimuli is similar with respect to the source locations and activation timings within SI and SII except that there were no detectable activations within area 3b following noxious stimulation.

A new method for measuring the conduction velocities of Aβ-, Aδ- and C-fibers following electric and CO2 laser stimulation in humans

Abstract The conduction velocities of Aβ-, Aδ- and C-fibers of a peripheral nerve of the upper limb in normal subjects were measured by a combination of conventional electric stimulation, painful CO 2 laser stimulation and non-painful CO 2 laser stimulation of a tiny skin surface area, respectively. The values obtained were 69.1±7.4 m/s, 10.6±2.1 and 1.2±0.2 m/s, respectively. These findings demonstrated that the combined methods are useful for experimental and clinical exploration of the physiological function and pathophysiological role of Aβ-, Aδ- and C-fibers of a given peripheral nerve.

Cerebral responses following stimulation of unmyelinated C-fibers in humans: electro- and magneto-encephalographic study.

There are two kinds of pain, a sharp pain ascending through Adelta fibers (first pain) and a second burning pain ascending though C fibers (second pain). By using a novel method, the application of a low intensity CO(2) laser beam to a tiny area of skin using a very thin aluminum plate with numerous tiny holes as a spatial filter, we succeeded in selectively stimulating unmyelinated C fibers of the skin in humans, and could record consistent and clear brain responses using electroencephalography (EEG) and magnetoencephalography (MEG). The conduction velocity (CV) of the C fibers of the peripheral nerve and spinal cord, probably spinothalamic tract (STT), is approximately 1-4 m/s, which is significantly slower than that of Adelta (approximately 10-15 m/s) and Abeta fibers (approximately 50-70 m/s). This method should be very useful for clinical application. Following C fiber stimulation, primary and secondary somatosensory cortices (SI and SII) are simultaneously activated in the cerebral hemisphere contralateral to the stimulation, and then, SII in the hemisphere ipsilateral to the stimulation is activated. These early responses are easily detected by MEG. Then, probably limbic systems such as insula and cingulate cortex are activated, and those activities reflected in EEG components. Investigations of the cortical processing in pain perception including both first and second pain should provide a better understanding of pain perception and, therefore, contribute to pain relief in clinical medicine.

Movements modulate cortical activities evoked by noxious stimulation

&NA; To evaluate the effects of movement on cortical activities evoked by noxious stimulation, we recorded magnetoencephalography following noxious YAG laser stimulation applied to the dorsum of the left hand in normal volunteers. Results of the present study can be summarized as follows: (1) active movement of the hand ipsilateral to the side of noxious stimulation resulted in significant attenuation of both primary and secondary somatosensory cortices (SI and SII) in the hemisphere contralateral to the stimulated hand (cSI and cSII). Activity in the hemisphere ipsilateral to the side of stimulation (iSII) was not affected. (2) Active movement of the hand contralateral to the side of noxious stimulation resulted in significant attenuation of cSII. Activity in cSI and iSII was not affected. (3) Passive movement of the hand ipsilateral to the side of noxious stimulation resulted in significant attenuation of cSI. Activity in cSII and iSII was not affected. (4) Visual analogue scale (VAS) changes showed a similar pattern to the amplitude changes of cSII. These results suggest that activities in three regions are modulated by movements differently. Inhibition in cSI was considered to be mainly due to an interaction in SI by the signals ascending from the stimulated and movement hand. Inhibition in cSII was considered to be mainly due to particular brain activities relating to motor execution and/or movement execution associated with a specific attention effect. In addition, since VAS changes showed a similar relationship with the amplitude changes of cSII, cSII may play a role in pain perception.

Conduction velocity of the spinothalamic tract following CO2 laser stimulation of C-fibers in humans.

&NA; Pain‐related somatosensory‐evoked potential following CO2 laser stimulation (laser‐evoked potential (LEP)) is now used not only for research objectives, but also for clinical applications. Estimating the conduction velocity (CV) of the spinothalamic tract (STT) by analyzing LEP following activation of A&dgr;‐fibers (A&dgr;‐CVSTT) by CO2 laser stimulation has been performed previously, but estimating the CV of STT following activation of C‐fibers (C‐CVSTT) has not. This is the first report to estimate the C‐CVSTT in humans; by using the novel method of CO2 laser stimulation applied to tiny skin areas. The calculation method was based on that of Kakigi and Shibasaki (Electroenceph clin Neurophysiol 80 (1991) 39) who measured A&dgr;‐CVSTT by conventional CO2 laser stimulation. The C‐CVSTT ranged between 1.4 and 4.0 m/s, and its mean±SD was 2.9±0.8 m/s. This C‐CVSTT was significantly slower than the A&dgr;‐CVSTT, which ranged approximately from 10 to 21 m/s. The nociceptive signal of the C‐fibers in STT is probably conveyed by unmyelinated axons of projection neurons to reach the thalamus. Our findings provide the first physiological evidence of the signals ascending through unmyelinated axons in the spinal cord in humans. In addition, estimating C‐CVSTT and A&dgr;‐CVSTT combined with conventional methods to measure the CV of the posterior column using electrical stimulation should be useful and have important clinical applications, particularly in patients with spinal cord lesions showing various kinds of sensory disturbances.

Cerebral activation by the signals ascending through unmyelinated C-fibers in humans: a magnetoencephalographic study

Cerebral processing of first pain, associated with A delta-fibers, has been studied intensively, but the cerebral processing associated with unmyelinated C-fibers, relating to second pain, remains to be investigated. This is the first study to clarify the primary cortical processing of second pain by magnetoencephalography, through the selective activation of C-fibers, by the stimulation of a tiny area of skin with a CO2 laser. In the hemisphere contralateral to the side stimulated, a one-source generator in the upper bank of the Sylvian fissure (secondary somatosensory cortex, SII) or two-source generators in SII and the hand area of the primary somatosensory cortex (SI) were the optimal configurations for the first component 1M. The onset and peak latency of the two sources in SI and SII were not significantly different. In the hemisphere ipsilateral to the stimulation, only one source was estimated in SII, and its peak latency was significantly (approximately 18 ms on average) longer than that of the SII source in the contralateral hemisphere. From our findings we suggest that parallel activation of SI and SII contralateral to the stimulation represents the first step in the cortical processing of C-fiber-related activities, probably related to second pain.

Pain-related magnetic fields evoked by intra-epidermal electrical stimulation in humans.

OBJECTIVES We recently developed a new method for the preferential stimulation of Adelta fibers in humans. The aim of the present study was to examine whether this method can serve as an appropriate stimulus in a magnetoencephalographic study. METHODS We recorded somatosensory-evoked magnetic fields (SEFs) following intra-epidermal electrical stimulation applied to the hand and elbow. Superficial parts of the skin were electrically stimulated through a needle electrode whose tip was inserted in the epidermis. RESULTS In all 13 subjects, the equivalent current dipole was estimated in the secondary somatosensory cortices (SII). In 5 out of 13 subjects, simultaneous activation of the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulation was identified. The mean peak latencies of magnetic fields corresponding to contralateral SI, SII and ipsilateral SII activation following hand stimulation were 162, 158 and 171 ms, respectively. The respective latency following elbow stimulation was 137, 139 and 157 ms, respectively. Estimated peripheral conduction velocity was 15.6m/s. CONCLUSIONS All the results were consistent with previous findings in pain SEF studies. We concluded that our novel intra-epidermal electrical stimulation is useful for pain SEF studies since it does not need special equipment and is easy to control.

Sensory perception during sleep in humans: a magnetoencephalograhic study

We reported the changes of brain responses during sleep following auditory, visual, somatosensory and painful somatosensory stimulation by using magnetoencephalography (MEG). Surprisingly, very large changes were found under all conditions, although the changes in each were not the same. However, there are some common findings. Short-latency components, reflecting the primary cortical activities generated in the primary sensory cortex for each stimulus kind, show no significant change, or are slightly prolonged in latency and decreased in amplitude. These findings indicate that the neuronal activities in the primary sensory cortex are not affected or are only slightly inhibited during sleep. By contrast, middle- and long-latency components, probably reflecting secondary activities, are much affected during sleep. Since the dipole location is changed (auditory stimulation), unchanged (somatosensory stimulation) or vague (visual stimulation) between the state of being awake and asleep, different regions responsible for such changes of activity may be one explanation, although the activated regions are very close to each other. The enhancement of activities probably indicates two possibilities, an increase in the activity of excitatory systems during sleep, or a decrease in the activity of some inhibitory systems, which are active in the awake state. We have no evidence to support either, but we prefer the latter, since it is difficult to consider why neuronal activities would be increased during sleep.