Warm-, hot- and pain-related neural activities depending on baseline skin temperatures.

BACKGROUND: This study investigated the characteristics of temperature-related evoked neural activities to baseline skin temperatures on target and adjacent sites using contact heat evoked potentials (CHEPs). METHODS: Contact heat evoked potentials were recorded from 12 normal subjects during three stimuli: target temperatures for "warm", "hot" and "pain" were set at 41, 46 and 51 °C, respectively. The baseline temperature was separately set at 30, 35 and 40 °C under all conditions, and a heat pulse was delivered over the right forearm at 41 °C under the warm condition, at 46 °C under the hot condition and at 51 °C under the pain condition. RESULTS: The N2-P2 amplitude was significantly larger at the 40 °C baseline than at the 30 and 35 °C baselines during the pain condition, whereas no significant differences were observed during the hot and warm conditions. In addition, the effects of an interference warm stimulation to adjacent sites were examined; however, no significant effects were observed. CONCLUSIONS: These results suggest that the priming effects of temperature on CHEPs were only observed under the pain condition, indicating the specificity of thermal pain, as well as a difference in the neural mechanisms responsible for thermal noxious and innocuous processing in human brains. SIGNIFICANCE: This study using CHEPs shows the importance of baseline and target skin temperatures to investigate the characteristics of temperature-related neural activities. This measure may contribute to understanding of warm-, hot-, and pain-related neural activities in human brains.

Heat stress-induced phosphorylation of FoxO3a signalling in rat skeletal muscle.

AIM: A recent study demonstrated that FoxO3a was directly induced by the overexpression of Hsp72 in rat soleus muscle. However, whether heat stress treatment induces FoxO3a phosphorylation in rat skeletal muscle remains unclear. This study examined the effects of heat stress on the regulation of the FoxO3a signalling pathway in rat skeletal muscle. METHODS: Thirty-two male Wistar rats (15 weeks old) were randomly assigned into two groups; sedentary control group (Sed, n = 8) and experimental group (n = 24). After an overnight fast, one leg of each rat (HS leg) in the experimental group was immersed in hot water (43 °C) for 30 min, and the soleus and plantaris muscles in both legs were removed immediately (0 min), 30 min, 60 min, or 24 h after the heat stress (n = 6 each group). The contralateral, non-heated leg in the experimental group served as an internal control (CT leg). RESULTS: Heat stress treatment resulted in a significant increase in FoxO3a phosphorylation (Ser253) in the soleus and plantaris muscles of heat-stressed legs after 24 h. Hsp72 expression in heat-stressed legs was significantly higher at 60 min and 24 h in these muscles. Activation of the PTEN/Akt and MEK/ERK pathways was also observed in these muscles immediately after stress, but not at 24 h. There were no differences in FoxO1 and AMPKα phosphorylation in either muscle. CONCLUSION: Heat stress in rat skeletal muscle induces phosphorylation of FoxO3a signalling, and it may be related to Hsp72 upregulation, and the activation of the PTEN/Akt and MEK/ERK pathways.

Effects of walking combined with restricted leg blood flow on mTOR and MAPK signalling in young men.

UNLABELLED: Walking combined with blood flow reduction (BFR-walk) elicits muscle hypertrophy. However, the skeletal muscle intracellular signalling behind this response is currently unknown. AIM: To investigate the effects of BFR-walk on mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) signalling pathways in young men. METHODS: Six young men performed 20 min of treadmill walking at 55% of their predetermined maximum oxygen uptake. A pressure cuff belt was applied to the most proximal thigh of only one leg (BFR-Leg, external compression was 240 mmHg), whereas the other leg (CON-Leg) was without BFR during walking. Muscle biopsies were taken from the vastus lateralis of the CON-Leg before exercise and in both legs 3 h after exercise. RESULTS: Erk1/2 phosphorylation levels were significantly (P < 0.05) increased after exercise in both legs; however, only the BFR-Leg saw an increased phosphorylation of p38. For mTOR signalling, there were no changes in Akt, mTOR or S6K1 phosphorylation levels before or after walking. However, eEF2 phosphorylation level was significantly (P < 0.05) lower for the BFR-Leg 3 h after walking compared with CON-Leg. CONCLUSION: BFR-walk exercise may activate some intracellular signalling cascades that are associated with muscle hypertrophy in young men.

Heat stress activates the Akt/mTOR signalling pathway in rat skeletal muscle.

AIM: It is well known that various stimuli, such as mechanical stress and nutrients, induce muscle hypertrophy thorough the Akt/mTOR signalling pathway, which is a key mediator of protein synthesis and hypertrophy in skeletal muscle. It was recently reported that heat stress also induces an increase in muscle weight and muscle protein content. In addition, heat stress enhances Akt/mTOR signalling after one bout of resistance exercise. However, it remains unclear whether increased temperature itself stimulates the Akt/mTOR signalling pathway. METHODS: Forty-two male Wistar rats (279.5 ± 1.2 g) were divided into a control group (CON) or one of five thermal stress groups at 37, 38, 39, 40 or 41 °C (n = 7 each group). After overnight fasting, both legs were immersed in different temperatures of hot water for 30 min under sodium pentobarbital anaesthesia. The soleus and plantaris muscles were immediately removed from both legs after the thermal stress. RESULTS: The phosphorylation of mTOR or 4E-BP1 and heat shock protein (HSP) expression levels were similar among groups in both the soleus and plantaris muscles. However, Akt and p70S6K phosphorylation significantly increased at 41 °C in the soleus and plantaris muscles. Moreover, we observed a temperature-dependent increase in Akt and p70S6K phosphorylation in both muscles. CONCLUSION: Our data indicate that the altered temperature increased phosphorylation in a temperature-dependent manner in rat skeletal muscle and may itself be a key stimulator of Akt/mTOR signalling.

Effects of acute nicotine on somatosensory change-related cortical responses.

Nicotine is known to have enhancing effects on some aspects of attention and cognition. As for the pre-attentive processes of detecting sensory changes, nicotine has significant effects on the auditory and visual systems implying that its pre-attentive effect is common among sensory modalities. The purpose of the present study was to elucidate whether acute nicotine administration has enhancing effects in the somatosensory system. Change-related cortical activity in response to an abrupt increase in stimulus intensity was recorded using magnetoencephalography. The test stimulus consisted of standard electrical pulses at 100 Hz for 500 ms applied to the dorsum of the left hand followed by 0.7-mA stronger pulses for 300 ms. Nicotine was administered in a gum (4 mg of nicotine). Eleven healthy nonsmokers were tested with a double-blind and placebo-controlled design. Effects of nicotine on the cortical response in the primary (S1) and secondary (S2) somatosensory cortices were investigated. Results showed that nicotine failed to affect the S1 response while it significantly increased the amplitude of S2 activity in the hemisphere ipsilateral to the stimulation, and shortened the peak latency of S2 activity in both hemispheres. Since cortical responses in the present study represent a pre-attentive automatic process to encode new somatosensory events, the results suggest that nicotine can exert beneficial cognitive effects without a direct impact on attention and that the effect of nicotine on the automatic change-detecting system is common across sensory modalities.

Effects of ageing and endurance exercise training on alpha-actinin isoforms in rat plantaris muscle.

AIM: We recently reported that α-actinin adaptation occurs at the isoform level. This study was undertaken to clarify the effects of: (1) ageing-induced shift of myosin heavy chain (MyHC) composition and (2) endurance exercise training on α-actinin isoforms in rat plantaris muscle. METHODS: Adult (18 mo) and old (28 mo) male Fischer 344 rats were assigned to either sedentary control or endurance exercise training groups. Animals in the training groups ran on a treadmill for 8 week with training intensity adjusted to be equal for adult and old groups. After the training was completed, the plantaris muscles were taken for analyses of α-actinin-2, α-actinin-3, and MyHC composition and metabolic enzyme activities. RESULTS: The proportion of type IIb MyHC was lower, and that of type I MyHC was higher in old animals than in adult animals. α-actinin-3 was significantly lower in old animals than in adult animals. No significant difference was found in α-actinin-2 and citrate synthase (CS) activity between adult and old animals. Citrate synthase activity was higher in trained animals than in sedentary animals. Endurance training produced a fast-to-slow shift within type II MyHC isoforms in both adult and old animals. α-actinin-2 was significantly higher in trained animals than in sedentary animals. No significant difference was found in α-actinin-3 between trained and sedentary animals. CONCLUSION: These results support the α-actinin adaptation at the isoform level and show that the α-actinin-3 expression depends on the amount of type II MyHC, whereas α-actinin-2 expression is associated with improvement of muscular aerobic capacity.

Effects of prior sustained tactile stimulation on the somatosensory response to the sudden change of intensity in humans: an magnetoencephalography study.

The rapid detection of sensory changes is important to survival. The change-detection system should relate closely to memory since it requires the brain to separate a new stimulus from past sensory status. To clarify effects of past sensory status on processing in the human somatosensory cortex, brain responses to an abrupt change of intensity in a train of electrical pulses applied to the hand were recorded by magnetoencephalography (MEG). In Experiment 1, effects of the magnitude of deviance (1.0, 0.5, 0.3, 0.2, and 0.1 mA) between conditioning and test stimuli were examined. In Experiment 2, effects of the duration of the conditioning stimulus (3, 1.5, 1.0, and 0.5 s) were examined. The abrupt change in stimulus intensity activated the contralateral primary (cSI) and secondary somatosensory cortex (cSII). The amplitude of the cSI and cSII activity was dependent on not only the magnitude of the change in intensity but also the length of the conditioning stimulus prior to the change, suggesting that storage of prior tactile information was involved in generating these responses. The possibility that an activity of onset (with no conditioning stimulus) would be involved in the change-related activity was also discussed.

Developmental changes in point-light walker processing during childhood and adolescence: an event-related potential study.

To investigate developmental changes in the neural responses to a biological motion stimulus, we measured event-related potentials (ERPs) in 50 children aged from 7 to 14 years, and 10 adults. Two kinds of visual stimuli were presented: a point-light walker (PLW) stimulus and a scrambled point-light walker (sPLW) stimulus as a control. The sPLW stimulus had the same number of point-lights and the same velocity vector of point-lights as the PLW stimulus, but the initial starting positions were randomized. Consistent with previous ERP studies, one positive peak (P1) and two negative peaks (N1 and N2) were observed at around 130, 200 and 330 ms, respectively, in bilateral occipitotemporal regions, in all age groups. The latency of the P1 component was significantly shorter for the PLW than sPLW stimulus in all age groups, whereas the amplitude was significantly larger for the PLW than sPLW stimulus only for the 7-year-old group. The P1 amplitude and N1 latency were linearly decreased with age. The negative amplitudes of both N1 and N2 components of the PLW stimulus were significantly larger than those of the sPLW stimulus in all age groups. P1-N1 amplitude was changed by development, but not N2 amplitude. These results suggest that the intensity (P1) and timing (N1) of early visual processing for the PLW stimulus changed linearly throughout childhood and P1-N1 amplitude at occipitotemporal electrodes and N1 latency in 10-year-olds, but not 11-year-olds, was significantly larger than that in adults. For the amplitudes of the N2 component in response to PLW and sPLW stimuli in 7-8-year-old subjects were not statistically different from those in adults at occipitotemporal electrodes. These results suggest that the neural response to the PLW stimulus has developed by 10 years of age at the occipitotemporal electrode.

Visual motion direction is represented in population-level neural response as measured by magnetoencephalography.

We investigated whether direction information is represented in the population-level neural response evoked by the visual motion stimulus, as measured by magnetoencephalography. Coherent motions with varied speed, varied direction, and different coherence level were presented using random dot kinematography. Peak latency of responses to motion onset was inversely related to speed in all directions, as previously reported, but no significant effect of direction on latency changes was identified. Mutual information entropy (IE) calculated using four-direction response data increased significantly (>2.14) after motion onset in 41.3% of response data and maximum IE was distributed at approximately 20 ms after peak response latency. When response waveforms showing significant differences (by multivariate discriminant analysis) in distribution of the three waveform parameters (peak amplitude, peak latency, and 75% waveform width) with stimulus directions were analyzed, 87 waveform stimulus directions (80.6%) were correctly estimated using these parameters. Correct estimation rate was unaffected by stimulus speed, but was affected by coherence level, even though both speed and coherence affected response amplitude similarly. Our results indicate that speed and direction of stimulus motion are represented in the distinct properties of a response waveform, suggesting that the human brain processes speed and direction separately, at least in part.

Neural basis of stable perception of an ambiguous apparent motion stimulus.

Although it has been shown that an alternative dominant percept induced by an ambiguous visual scene has neural correlates in various cortical areas, it is not known how such a dominant percept is maintained until it switches to another. We measured the primary visual response to the two-frame bistable apparent motion stimulus (stroboscopic alternative motion) when observers continuously perceived one motion and compared this with the response for another motion using magnetoencephalography. We observed a response component at around 160 ms after the frame change, the amplitude of which depended on the perceived motion. In contrast, brain responses to less ambiguous and physically unambiguous motions in both the horizontal and vertical directions did not evoke such a component. The differential response evoked by the bistable apparent motion is therefore distinct from directionally-selective visual responses. The results indicate the existence of neural activity related to establish and maintain one dominant percept, the magnitude of which is related to the ambiguity of the stimulus. This is in the line with the currently proposed idea that dominant percept is established in the distributed cortical areas including the early visual areas. Further, the existence of the neural activity induced only by the ambiguous image suggests that the competitive neural activities for the two possible percepts exist even when one dominant image is continuously perceived.

Different adaptations of alpha-actinin isoforms to exercise training in rat skeletal muscles.

AIM: Alpha (alpha)-actinins are located in the skeletal muscle Z-line and form actin-actin cross-links. Mammalian skeletal muscle has two isoforms: alpha-actinin-2 and alpha-actinin-3. However, the response of alpha-actinin to exercise training is little understood. Therefore, the current study examined the effects of exercise training on the expression level of two alpha-actinin isoforms in skeletal muscles. METHODS: Twelve male Wistar rats were assigned randomly to a control (C; n = 6) or exercise training (T; n = 6) group. After T animals were trained on an animal treadmill for 9 weeks, alpha-actinin-2 and alpha-actinin-3 levels in the plantaris, white and red gastrocnemius muscles were analysed. In addition, changes in the myosin heavy chain (MyHC) composition were assessed, and muscle bioenergetic enzyme activities were measured. RESULTS: Results show that exercise training increased alpha-actinin-2 expression levels in all muscles (P < 0.05). However, no significant difference was found in alpha-actinin-3 expression levels between C and T animals. Subsequent MyHC analyses of all muscle showed an MyHC shift with direction from IIb to IIa. Furthermore, enzymatic analysis revealed that exercise training improved enzyme activities related to aerobic metabolism. CONCLUSION: The results of this study demonstrate that exercise training alters the expression level of alpha-actinin at the isoform level. Moreover, the increase in expression levels of alpha-actinin-2 is apparently related to alteration of skeletal muscle: its aerobic capacity is improved.

Neural processes of attentional inhibition of return traced with magnetoencephalography.

Inhibition of return (IOR) is a phenomenon that involves reaction times (RTs) to a spatially cued target that are longer than RTs to an uncued target when the interval between the cue and target is prolonged. Although numerous studies have examined IOR, no consensus has yet been reached regarding the neural mechanisms responsible for it. We used magnetoencephalography (MEG) and measured the human neural responses underlying the time course of IOR, applying a typical spatial cueing paradigm. The cue-target interval was 600+/-200 ms. Three experimental conditions were employed. Cued; the cue and target were presented at the same location. Uncued; the two stimuli were presented at opposite locations. Neutral; the cue stimulus was presented bilaterally. We found differences in the amplitudes of signals in the postero-temporal and bilateral temporal areas, and peak latencies in a central area between the cued and uncued conditions. These signals were localized to the extrastriate cortex, bilateral temporal-parietal junction (TPJ), and primary motor cortex, respectively. Bilateral TPJ activities are related to the identification of salient events in the sensory environment both within and independent of the current behavioral context and may play an important role in IOR in addition to extrastriate and the primary motor cortex.

Recommendations for the clinical use of somatosensory-evoked potentials.

The International Federation of Clinical Neurophysiology (IFCN) is in the process of updating its Recommendations for clinical practice published in 1999. These new recommendations dedicated to somatosensory-evoked potentials (SEPs) update the methodological aspects and general clinical applications of standard SEPs, and introduce new sections dedicated to the anatomical-functional organization of the somatosensory system and to special clinical applications, such as intraoperative monitoring, recordings in the intensive care unit, pain-related evoked potentials, and trigeminal and pudendal SEPs. Standard SEPs have gained an established role in the health system, and the special clinical applications we describe here are drawing increasing interest. However, to prove clinically useful each of them requires a dedicated knowledge, both technical and pathophysiological. In this article we give technical advice, report normative values, and discuss clinical applications.

Characteristics of sensori-motor interaction in the primary and secondary somatosensory cortices in humans: a magnetoencephalography study.

We studied sensori-motor interaction in the primary (SI) and secondary somatosensory cortex (SII) using magnetoencephalography. Since SII in both hemispheres was activated following unilateral stimulation, we analyzed SIIc (contralateral to stimulation) as well as SIIi (ipsilateral to stimulation). Four tasks were performed in human subjects in which a voluntary thumb movement of the left or right hand was combined with electrical stimulation applied to the index finger of the left or right hand: L(M)-L(S) (movement of the left thumb triggered stimulation to the left finger), L(M)-R(S) (movement of the left thumb triggered electrical stimulation to the right finger), R(M)-R(S) (movement of the right thumb triggered electrical stimulation to the right finger), and R(M)-L(S) (movement of the right thumb triggered electrical stimulation to the left finger). Stimulation to the index finger only (S condition) was also recorded. In SI, the amplitude of N20m and P35m was significantly attenuated in the R(M)-R(S) and L(M)-L(S) tasks compared with the S condition, but that for other tasks showed no change, corresponding to a conventional gating phenomenon. In SII, the R(M)-L(S) task significantly enhanced the amplitude of SIIc but reduced that of SIIi compared with the S condition. The L(M)-L(S) and R(M)-R(S) tasks caused a significant enhancement only in SIIi. The L(M)-R(S) task enhanced the amplitude only in SIIc. The laterality index showed that SII modulation with voluntary movement was more dominant in the hemisphere ipsilateral to movement but was not affected by the side of stimulation. These results provided the characteristics of activities in somatosensory cortices, a simple inhibition in SI but complicated changes in SII depending on the side of movement and stimulation, which may indicate the higher cognitive processing in SII.

Backward-masking: the effect of the duration of the second stimulus on recognition of the first stimulus.

OBJECTIVE: We recorded event-related magnetic fields following a target stimulus followed by a masking stimulus to investigate the visual backward masking effect using a helmet-type magnetoencephalography system in humans. METHODS: In the target stimulus with masking stimulus conditions, duration of the target stimulus was constant at 16 ms, and duration of the masking stimulus was altered (16, 48 and 144 ms). The target stimulus was masked by the 144-ms masking stimulus, but not by the 16-ms masking stimulus, and was obscured by the 48-ms masking stimulus. For control conditions (Single-condition), event-related magnetic fields were recorded following the sole presentation of the masking stimulus for 32, 64 or 160 ms. RESULTS: One major response was obtained at 180 ms after the onset of the stimulation in each condition. The equivalent current dipole of one major response was estimated to lie in the occipital lobe, but there was a relatively large inter-individual difference. There was no significant difference in latency between the target stimulus with masking stimulus conditions and Single-conditions. In the target stimulus with masking stimulus conditions with the 48- and 144-ms masking stimulus, the root mean square value did not differ from that in the respective Single-condition, while the root mean square value for the target stimulus with masking stimulus conditions with the 16-ms masking stimulus was significantly smaller than that in the Single-condition with the 32-ms masking stimulus, but not different from that in the Single-condition with the 16-ms masking stimulus. CONCLUSIONS: The peak latency of one major response depended on the onset of the first stimulus for both the target stimulus with masking stimulus conditions and Single-condition, but the root mean square value depended on the duration of the masking stimulus. We concluded that the temporal information for the target stimulus was preserved during the masking effect, while the figural information was interrupted by the masking stimulus. Our results suggested that temporal factors for the stimulus were processed differently from those responsible for the object's recognition during backward masking.

The dependence of the auditory evoked N1m decrement on the bandwidth of preceding notch-filtered noise.

The auditory evoked response is known to be changed by a preceding sound. In this study we investigated by means of magnetoencephalography how a preceding notch-filtered noise (NFN) with different bandwidths influences the human auditory evoked response elicited by the following test stimulus. We prepared white noise (WN) and four NFNs which were derived from WN by suppressing frequency regions around 1 kHz with 1/8-, 1/4-, 1/2- and 1-octave bandwidths. Stimulation for 3 s with this set of noises resulted in differences in responsiveness to a 1-kHz test tone presented 500 ms after the offset of the noises. The N1m response to the 1-kHz test tone stimulus was at a minimum when the preceding NFN had 1/4-octave stop-band frequencies as compared with 1/8-, 1/2- and 1-octave NFN and WN. This N1m decrement is explained by the imbalanced neural activities caused by habituation and lateral inhibition in the auditory system. The results contribute to understanding of the inhibitory system in the human auditory cortex.

Changes in the centrifugal gating effect on somatosensory evoked potentials depending on the level of contractile force.

In this study, we investigated the somatosensory evoked potentials (SEPs) during the preparatory period of self-initiated plantar flexion at different force levels of muscle contraction and elucidated the mechanism behind the centrifugal gating effect on somatosensory information processing. We recorded SEPs following stimulation of the tibial nerve at the popliteal fossa during the preparatory period of a 20% maximal voluntary contraction (MVC) and 50% MVC. The preparatory period was divided into two sub-periods based on the components of movement-related cortical potentials, the negative slope (NS sub-period) and the Bereitschaftspotential (BP sub-period). The subjects were instructed to concentrate on the movement and not to pay attention to the continuous electrical stimulation. Pre-movement SEPs were averaged separately during the two sub-periods under each MVC condition. The mean amplitudes of BP and NS were larger during the 50% MVC than the 20% MVC. As for the components of SEPs, during the NS sub-period the amplitude of P30 under the 50% MVC and N40 under both conditions were significantly smaller than that in the stationary sequence, and N40 amplitude was significantly smaller during the 50% MVC than the 20% MVC. During the BP sub-period, the amplitude of P30 and N40 during the 50% MVC was significantly smaller than during the stationary sequence, while it was not significantly different between the 20% and 50% MVCs. In conclusion, the extent of the centrifugal gating effect on SEPs was dependent on the activities of motor-related areas, which generated the NS and BP.

N1m recovery from decline after exposure to noise with strong spectral contrasts.

Comb-filtered noise (CFN, derived from white noise by suppressing regularly spaced frequency regions) was presented for 3 s followed by two types of test stimuli. One test stimulus (SB) was comprised of spectra centered in the stop-band regions of the CFN and the other test stimulus (PB) of spectra centered in the band pass regions of the CFN. Magnetoencephalographically recorded N1m responses evoked by SB stimuli were decreased relative to the N1m response evoked by PB stimuli. This effect was maximal when the interval between the CFN and test stimuli was short (0.5 s) but was detected at intervals up to 2 s. The results suggest lateral inhibition in the auditory cortex and point to a decay of inhibition lasting on the order of seconds.

Cortical responses to noxious stimuli during sleep.

We used magnetoencephalography to study effects of sleep on cortical responses to noxious stimuli and to clarify the mechanisms underlying pain perception. For a noxious stimulus, painful intra-epidermal electrical stimulation, which selectively activates A-delta fibers, was applied to the dorsum of the left hand. While awake, subjects were asked to count the number of stimuli silently (Attention) or ignore the stimuli (Control). During sleep, magnetic fields recorded in stage 1 sleep and stage 2 sleep were analyzed. One main component at a latency around 140-160 ms was identified in the awake condition. Multiple source analysis indicated that this main component was generated by activities in the contralateral primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII) and insular cortex. The medial temporal area (MT) and cingulate cortex were activated later than the main component. Cortical responses in the contralateral SI, ipsilateral SII and MT, bilateral insula and cingulate cortex were significantly enhanced in Attention as compared with Control. The main component 1 M as well as later magnetic fields were markedly attenuated during sleep, suggesting that all these cortical areas are involved in pain cognition.

Facilitation of A[delta]-fiber-mediated acute pain by repetitive transcranial magnetic stimulation.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex modulates acute and chronic pain perception. The authors previously showed that rTMS over the primary motor cortex (M1) inhibited capsaicin-induced acute pain ascending through C-fibers. OBJECTIVE: To investigate the effects of 1-Hz rTMS over M1 on acute experimentally induced pain mediated by Adelta-fibers (i.e., another type of acute pain). METHODS: The authors examined whether rTMS over M1 affected laser evoked potentials (LEPs) in 13 normal subjects using thulium: yttrium-aluminum-garnet laser stimulation. Subjective pain-rating scores and LEPs obtained under three different conditions--rTMS, realistic sham stimulation, and a control condition with no stimulation--were compared. RESULTS: The authors found that 1-Hz rTMS over M1 significantly aggravated the subjective pain and enhanced the N2-P2 amplitudes compared with the sham or control sessions. Because the pain-rating scores and the N2-P2 amplitudes correlated positively, the N2-P2 amplitudes in the present study can be regarded as the cortical correlate of subjective pain. CONCLUSIONS: Together with the authors' previous study on C-fiber pain, this facilitatory effect of repetitive transcranial magnetic stimulation on Adelta-fiber-mediated further strengthens the notion of a relationship between repetitive transcranial magnetic stimulation over M1 and pain perception.