[Show abstract][Hide abstract] ABSTRACT: Skin pain and muscle pain are categorically distinct from each other. While skin pain is a sharp, spatially localized sensation, muscle pain is a dull, poorly localized and more unpleasant one. We hypothesized that there are specific brain regions preferentially activated by muscle pain compared to skin pain. To test this hypothesis, brain responses were recorded from 13 normal male subjects in response to repeated painful electrical stimulation of the muscle and skin of the left leg, using 3-T magnetic resonance imaging scanner. The common brain regions that responded to painful stimulations of both skin and muscle were the thalamus, anterior cingulate cortex, bilateral insula, contralateral primary and secondary somatosensory cortices, and ipsilateral cerebellum. Brain regions specifically activated by muscle stimulation were the midbrain, bilateral amygdala, caudate, orbitofrontal cortex, hippocampus, parahippocampus and superior temporal pole, most of which are related to emotion. Regions except the midbrain showed contralateral preference. These results suggest that dull sensation, which is characteristic of muscular pain, is related with processing in these brain regions.
Neuroscience Research 07/2011; 70(3):285-93. DOI:10.1016/j.neures.2011.04.001 · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Event-related functional magnetic resonance imaging was used to investigate brain processing of the signals ascending from peripheral C and Adelta fibers evoked by phasic laser stimuli on the right hand in humans. The stimulation of both C and Adelta nociceptors activated the bilateral thalamus, bilateral secondary somatosensory cortex, right (ipsilateral) middle insula, and bilateral Brodmann's area (BA) 24/32, with the majority of activity found in the posterior portion of the anterior cingulate cortex (ACC). However, magnitude of activity in the right (ipsilateral) BA32/8/6, including dorsal parts in the anterior portion of the ACC (aACC) and pre-supplementary motor area (pre-SMA), and the bilateral anterior insula was significantly stronger following the stimulation of C nociceptors than Adelta nociceptors. It was concluded that the activation of C nociceptors, related to second pain, evokes different brain processing from that of Adelta nociceptors, related to first pain, probably due to the differences in the emotional and motivational aspects of either pain, which are mainly related to the aACC, pre-SMA, and anterior insula.
[Show abstract][Hide abstract] ABSTRACT: We used magnetoencephalography (MEG) to study effects of sleep on cortical responses to noxious stimuli and to clarify the mechanisms underlying pain perception. For a noxious stimulus, painful intraepidermal electrical stimulation (ES), 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 1M, as well as later magnetic fields, was markedly attenuated during sleep, suggesting that all these cortical areas are involved in pain cognition.
International Congress Series 03/2005; 1278:359-362. DOI:10.1016/j.ics.2004.11.108
[Show abstract][Hide abstract] ABSTRACT: We review the recent progress of electroencephalography (EEG) and magnetoencephalography (MEG) to elucidate pain perception mechanisms in humans, since EEG and MEG have an excellent temporal resolution in order of msec. MEG is more useful to detect activated areas following painful stimulation, because the spatial resolution of EEG is not very high. For recording activities following Adelta fiber stimulation relating to the first pain, painful CO2 laser stimulation is now widely used, but our new method, epidermal stimulation (ES), is also very useful. The primary small activity was recorded from the primary somatosensory cortex (SI), probably in area 1, in the hemisphere contralateral to the stimulation. Then, secondary somatosensory cortex (SII) and insula were activated with the second activity in SI. These 3 regions were activated in parallel with almost the same time period. This is a very characteristic finding in pain perception. Then, the cingulate cortex and medial temporal area (MT) around the amygdala and hippocampus were activated. In the hemisphere ipsilateral to the stimulation as well, the above regions were activated, except for SI. Therefore, we speculated that SI plays a main role in localization of the stimulus point, the SII and insula are important sites for pain perception, and the cingulate and MT are mainly responsible for cognitive or emotional aspects of pain perception. For recording activities following C fiber stimulation relating to the second pain, we recently developed a new method, that is, applying weaker CO2 laser stimuli to tiny areas of the skin. MEG findings following C fiber stimulation were also similar to those following Adelta fiber stimulation. However, the effects of sleep and attention on MEG following C fiber stimulation was much larger than that following Adelta fiber stimulation. This finding may suggest greater effects of cognitive or emotional functions on second pain than the first pain.
Journal of the Chinese Medical Association 09/2004; 67(8):377-86. · 0.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Using magnetoencephalography (MEG), we evaluated the cerebral regions relating to second pain perception ascending through C-fibers and investigated the effect of distraction on each region.
Thirteen normal subjects participated in this study. CO2 laser pulses were delivered to the dorsum of the left hand to selectively activate C-fibers. The MEG responses were analyzed using a multi-dipole model.
(1) primary somatosensory cortex (SI), and (2) secondary somatosensory cortex (SII)--insula were the main generators for the primary component, 1M, whose mean peak latency was 744 ms. In addition to (1) and (2), (3) cingulate cortex and (4) medial temporal area (MT) were also activated for the subsequent component, 2M, whose mean peak latency was 947 ms. During a mental calculation task (Distraction), all 6 sources were significantly reduced in amplitude, but the SII-insula (P < 0.01) and cingulate cortex (P < 0.001) were more sensitive than the SI (P < 0.05) and MT (P < 0.05).
We confirmed that SI in the contralateral hemisphere and SII-insula, cingulate cortex and MT in bilateral hemispheres play a major role in second pain perception, and all sites were much affected by a change of attention, indicating that these regions are related to the cognitive aspect of second pain perception.
The SI, SII, cingulate and MT were activated during the C-fiber-related MEG response, and responses in these regions were significantly diminished during mental distraction.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: We investigated C-fiber discharges and cerebral potentials evoked by weak CO(2) laser beams applied to a tiny skin area in five healthy subjects. Microneurography was performed from the peroneal nerve in the right popliteal area. Cerebral potentials were recorded from the Cz electrode referred to linked earlobes. The mean conduction velocity of five stable single units was 1.1+/-0.3 m/s. The mean latency of the positive peak of cerebral potentials was 1327.4+/-46.2 ms. These findings indicated that this new stimulation method selectively activated C-fiber nociceptors of the skin.
[Show abstract][Hide abstract] ABSTRACT: 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 Brodmann's 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.
European Journal of Neuroscience 12/2003; 18(10):2859-66. DOI:10.1111/j.1460-9568.2003.02995.x · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Sleep Medicine 12/2003; 4(6):493-507. DOI:10.1016/S1389-9457(03)00169-2 · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the effects of sleep on pain-related somatosensory evoked magnetic fields (SEFs) following painful electrical stimulation to identify the mechanisms generating them in both fast A-beta fibers relating to touch and slow A-delta fibers relating to pain. While the subjects were awake, non-painful and painful electrical stimulations were applied, and while asleep, painful stimulation was applied to the left index finger. During awake, five components (1M-5M) were identified following both non-painful and painful stimulation, but the 4M and 5M at around 70-100 ms and 140-180 ms, respectively, were significantly enhanced following painful stimulation. During sleep, 1M and 2M generated in the primary somatosensory cortex (SI) did not show a significant change, 3M in SI showed a slight but significant amplitude reduction, and 4M and 5M generated in both SI and the secondary somatosensory cortex (SII) were significantly decreased in amplitude or disappeared. The 4M and 5M are complicated components generated in SI and SII ascending through both A-beta fibers and A-delta fibers. They are specifically enhanced by painful stimulation due to an increase of signals ascending through A-delta fibers, and are markedly decreased during sleep, because they much involve cognitive function.
Cognitive Brain Research 08/2003; 17(2):388-99. DOI:10.1016/S0926-6410(03)00140-X · 3.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Neuroscience Research 04/2003; 45(3):255-75. DOI:10.1016/S0168-0102(02)00230-4 · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated effects of sleep on pain-related somatosensory evoked potentials (SEP) following painful electrical stimulation of the left index finger. The biggest advantage of this method is that signals ascending through both A-beta fibers relating to touch and A-delta fibers relating to pain can be recorded simultaneously. While the subject was awake, non-painful stimulation evoked early- and middle latency components, N20, P30 and N60, at the C4 electrode, and painful stimulation evoked not only early- and middle latency components at the C4 but also later pain-specific components, N130 and P240, at the Cz electrode. During sleep, N20 and P30 did not show a significant change in amplitude, N60 showed a slight but significant amplitude reduction, and N130 and P240 significantly decreased in amplitude or disappeared, as compared with those while awake. Therefore, we speculate on the mechanisms generating each component as follows; (1) N20 and P30 are the primary components generated in SI ascending through A-beta fibers. (2) N60 is the secondary component generated in SI involving cognitive function to some degree. (3) N130-P240 are the pain-specific components ascending through A-delta fibers, and closely related to cognitive function, because they were much affected by consciousness, different from the components ascending through A-beta fibers.
Neuroscience Research 02/2003; 45(1):53-7. DOI:10.1016/S0168-0102(02)00198-0 · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study is to evaluate the effects of attention, distraction and sleep on CO(2) laser-evoked potentials (LEP) relating to C-fibers (ultra-late LEP).
Non-painful CO(2) laser pulses were delivered to a tiny skin area of the dorsum of the right hand. Ultra-late LEP were recorded from 10 normal subjects in 5 different conditions: control (wakefulness), attention, distraction, drowsiness and sleep (stage 2).
The amplitude of ultra-late LEP was slightly increased during attention and significantly decreased during distraction, relative to the control. The ultra-late LEP decreased much in amplitude or almost disappeared during sleep. However, significant differences in latency among the conditions were not found.
We confirmed that the brain responses relating to signals ascending through C-fibers were much affected by the level of consciousness, being consistent with the findings of late LEP relating to Adelta-fibers. This is the first study to indicate the important characteristics of ultra-late LEP relating to consciousness, suggesting that they include cognitive function and also that one has to be careful of the change in alertness when recording.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: We measured the conduction velocity (CV) of C-fibers in the spinothalamic tract (STT) following stimulation with a CO(2) laser using a new method. We delivered non-painful laser pulses to tiny areas of the skin overlying the vertebral spinous processes at different levels from the 7(th) cervical (C7) to the 12(th) thoracic (T12), and recorded cerebral evoked potentials in 11 healthy men. We used the term "ultra-late laser evoked potentials" (ultra-late LEPs), since the peak latency was much longer than that for conventional LEPs related to Adelta-fibers following painful laser stimulation (late LEPs). The mean CV of C-fibers in the STT was 2.2+/-0.6 m/s, which was significantly lower than the CV of the Adelta-fibers (10.0+/-4.5 m/s). This technique is novel and simple, and should be useful as a diagnostic tool for assessing the level of spinal cord lesions.