2023/05/08 更新

写真a

キヌカワ トモアキ
絹川 友章
KINUKAWA Tomoaki
所属
医学部附属病院 麻酔科 病院講師
職名
病院講師
外部リンク

学位 1

  1. 医学博士 ( 2021年3月   名古屋大学 ) 

研究キーワード 3

  1. 区域麻酔

  2. 慢性疼痛

  3. DNIC

研究分野 1

  1. ライフサイエンス / 麻酔科学  / 内因性疼痛抑制能

学歴 1

  1. 名古屋大学   大学院医学系研究科   大学院医学系研究科

    2017年4月 - 2021年3月

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    国名: 日本国

所属学協会 4

  1. 麻酔科学会

  2. 日本集中治療学会

  3. 日本ペインクリニック学会

  4. 区域麻酔学会

 

論文 17

  1. Properties of echoic memory revealed by auditory-evoked magnetic fields

    Kinukawa Tomoaki, Takeuchi Nobuyuki, Sugiyama Shunsuke, Nishihara Makoto, Nishiwaki Kimitoshi, Inui Koji

    SCIENTIFIC REPORTS   9 巻 ( 1 ) 頁: 12260   2019年8月

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    記述言語:日本語   出版者・発行元:Scientific Reports  

    We used auditory-evoked magnetic fields to investigate the properties of echoic memory. The sound stimulus was a repeated 1-ms click at 100 Hz for 500 ms, presented every 800 ms. The phase of the sound was shifted by inserting an interaural time delay of 0.49 ms to each side. Therefore, there were two sounds, lateralized to the left and right. According to the preceding sound, each sound was labeled as D (preceded by a different sound) or S (by the same sound). The D sounds were further grouped into 1D, 2D, and 3D, according to the number of preceding different sounds. The S sounds were similarly grouped to 1S and 2S. The results showed that the preceding event significantly affected the amplitude of the cortical response; although there was no difference between 1S and 2S, the amplitudes for D sounds were greater than those for S sounds. Most importantly, there was a significant amplitude difference between 1S and 1D. These results suggested that sensory memory was formed by a single sound, and was immediately replaced by new information. The constantly-updating nature of sensory memory is considered to enable it to act as a real-time monitor for new information.

    DOI: 10.1038/s41598-019-48796-9

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  2. Mechanisms of Short- and Long-Latency Sensory Suppression: Magnetoencephalography Study

    Takeuchi Nobuyuki, Fujita Kohei, Taniguchi Tomoya, Kinukawa Tomoaki, Sugiyama Shunsuke, Kanemoto Kousuke, Nishihara Makoto, Inui Koji

    NEUROSCIENCE   514 巻   頁: 92 - 99   2023年3月

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    記述言語:英語   出版者・発行元:Neuroscience  

    Prepulse inhibition (PPI) is sensory suppression whose mechanism (i.e., whether PPI originates from specific inhibitory mechanisms) remains unclear. In this study, we applied the combination of short-latency PPI and long-latency paired pulse suppression in 17 healthy subjects using magnetoencephalography to investigate the mechanisms of sensory suppression. Repeats of a 25-ms pure tone without a blank at 800 Hz and 70 dB were used for a total duration of 1600 ms. To elicit change-related cortical responses, the sound pressure of two consecutive tones in this series at 1300 ms was increased to 80 dB (Test). For the conditioning stimuli, the sound pressure was increased to 73 dB at 1250 ms (Pre 1) and 80 dB at 700 ms (Pre 2). Six stimuli were randomly presented as follows: (1) Test alone, (2) Pre 1 alone, (3) Pre 1 + Test, (4) Pre 2 + Test, (5) Pre 2 + Pre 1, and (6) Pre 2 + Pre 1 + Test. The inhibitory effects of the conditioning stimuli were evaluated using N100m/P200m components. The results showed that both Pre 1 and Pre 2 significantly suppressed the Test response. Moreover, the inhibitory effects of Pre 1 and Pre 2 were additive. However, when both prepulses were present, Pre 2 significantly suppressed the Pre 1 response, suggesting that the Pre 1 response amplitude was not a determining factor for the degree of suppression. These results suggested that the suppression originated from a specific inhibitory circuit independent of the excitatory pathway.

    DOI: 10.1016/j.neuroscience.2022.11.016

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  3. Cortical activity during the wind-up of flexion reflex and pain: a magnetoencephalographic study using time-frequency analysis

    Taniguchi Tomoya, Kinukawa Tomoaki Alex, Takeuchi Nobuyuki, Sugiyama Shunsuke, Nishihara Makoto, Kida Tetsuo, Nishiwaki Kimitoshi, Inui Koji

    CEREBRAL CORTEX     2023年3月

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  4. The 40-Hz auditory steady-state response enhanced by beta-band subharmonics

    Sugiyama Shunsuke, Taniguchi Tomoya, Kinukawa Tomoaki, Takeuchi Nobuyuki, Ohi Kazutaka, Shioiri Toshiki, Nishihara Makoto, Inui Koji

    FRONTIERS IN NEUROSCIENCE   17 巻   頁: 1127040   2023年2月

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    記述言語:英語   出版者・発行元:Frontiers in Neuroscience  

    The 40-Hz auditory steady-state response (ASSR) has received special attention as an index of gamma oscillations owing to its association with various neuropsychiatric disorders including schizophrenia. When a periodic stimulus is presented, oscillatory responses are often elicited not only at the stimulus frequency, but also at its harmonic frequencies. However, little is known about the effect of 40-Hz subharmonic stimuli on the activity of the 40-Hz ASSR. In the present magnetoencephalography study, we focused on the nature of oscillation harmonics and examined oscillations in a wide frequency range using a time-frequency analysis during the 6.67-, 8-, 10-, 13.3-, 20-, and 40-Hz auditory stimuli in 23 healthy subjects. The results suggested that the 40-Hz ASSR represents activation of a specific circuit tuned to this frequency. Particularly, oscillations elicited by 13.3- and 20-Hz stimuli exhibited significant enhancement at 40 Hz without changing those at the stimulus frequency. In addition, it was found that there was a non-linear response to stimulation in the beta band. We also demonstrated that the inhibition of beta to low-gamma oscillations by the 40-Hz circuit contributed to the violation of the rule that harmonic oscillations gradually decrease at higher frequencies. These findings can advance our understanding of oscillatory abnormalities in patients with schizophrenia in the future.

    DOI: 10.3389/fnins.2023.1127040

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  5. ◎○△しかく 日本救急医学会専門医/日本ペインクリニック学会専門医

    藤原 辰也, 絹川 友章

    LiSA   29 巻 ( 11 ) 頁: 1064 - 1065   2022年11月

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    出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.3101202372

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  6. Suppression of Low-Frequency Gamma Oscillations by Activation of 40-Hz Oscillation

    Sugiyama Shunsuke, Taniguchi Tomoya, Kinukawa Tomoaki, Takeuchi Nobuyuki, Ohi Kazutaka, Shioiri Toshiki, Nishihara Makoto, Inui Koji

    CEREBRAL CORTEX   32 巻 ( 13 ) 頁: 2785 - 2796   2022年6月

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    記述言語:英語   出版者・発行元:Cerebral Cortex  

    Gamma oscillations have received considerable attention owing to their association with cognitive function and various neuropsychiatric disorders. However, interactions of gamma oscillations at different frequency bands in humans remain unclear. In the present magnetoencephalographic study, brain oscillations in a wide frequency range were examined using a time-frequency analysis during the 20-, 30-, 40-, and 50-Hz auditory stimuli in 21 healthy subjects. First, dipoles for auditory steady-state response (ASSR) were estimated and interaction among oscillations at 10-60 Hz was examined using the source strength waveforms. Results showed the suppression of ongoing low-gamma oscillations at approximately 30 Hz during stimulation at 40 Hz. Second, multi-dipole analyses suggested that the main dipole for ASSR and dipoles for suppressed low-frequency gamma oscillations were distinct. Third, an all-sensor analysis was performed to clarify the distribution of the 40-Hz ASSR and suppression of low-frequency gamma oscillations. Notably, the area of suppression surrounded the center of the 40-Hz ASSR and showed a trend of extending to the vertex, indicating that different groups of neurons were responsible for these two gamma oscillations and that the 40-Hz oscillation circuit have specific inhibitory innervation to the low-gamma circuit.

    DOI: 10.1093/cercor/bhab381

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  7. Mechanisms of Long-Latency Paired Pulse Suppression: MEG Study

    Takeuchi Nobuyuki, Fujita Kohei, Taniguchi Tomoya, Kinukawa Tomoaki, Sugiyama Shunsuke, Kanemoto Kousuke, Nishihara Makoto, Inui Koji

    BRAIN TOPOGRAPHY   35 巻 ( 2 ) 頁: 241 - 250   2022年3月

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    記述言語:日本語   出版者・発行元:Brain Topography  

    Paired pulse suppression is an electrophysiological method used to evaluate sensory suppression and often applied to patients with psychiatric disorders. However, it remains unclear whether the suppression comes from specific inhibitory mechanisms, refractoriness, or fatigue. In the present study, to investigate mechanisms of suppression induced by an auditory paired pulse paradigm in 19 healthy subjects, magnetoencephalography was employed. The control stimulus was a train of 25-ms pure tones of 65 dB SPL for 2500 ms. In order to evoke a test response, the sound pressure of two consecutive tones at 2200 ms in the control sound was increased to 80 dB (Test stimulus). Similar sound pressure changes were also inserted at 1000 (CS2) and 1600 (CS1) ms as conditioning stimuli. Four stimulus conditions were used; (1) Test alone, (2) Test + CS1, (3) Test + CS1 + CS2, and (4) Test + CS2, with the four sound stimuli randomly presented and cortical responses averaged at least 100 times for each condition. The baseline-to-peak and peak-to-peak amplitudes of the P50m, N100m, and P200m components of the test response were compared among the four conditions. In addition, the response to CS1 was compared between conditions (2) and (3). The results showed significant test response suppression by CS1. While the response to CS1 was significantly suppressed when CS2 was present, it did not affect suppression of the test response by CS1. It was thus suggested that the amplitude of the response to a conditioning stimulus is not a factor to determine the inhibitory effects of the test response, indicating that suppression is due to an external influence on the excitatory pathway.

    DOI: 10.1007/s10548-021-00878-6

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  8. A Minimally Invasive Method for Observing Wind-Up of Flexion Reflex in Humans: Comparison of Electrical and Magnetic Stimulation

    Taniguchi Tomoya, Kinukawa Tomoaki Alex, Takeuchi Nobuyuki, Sugiyama Shunsuke, Nishihara Makoto, Nishiwaki Kimitoshi, Inui Koji

    FRONTIERS IN NEUROSCIENCE   16 巻   頁: 837340   2022年2月

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    記述言語:日本語   出版者・発行元:Frontiers in Neuroscience  

    Wind-up like pain or temporal summation of pain is a phenomenon in which pain sensation is increased in a frequency-dependent manner by applying repeated noxious stimuli of uniform intensity. Temporal summation in humans has been studied by observing the increase in pain or flexion reflex by repetitive electrical or thermal stimulations. Nonetheless, because the measurement is accompanied by severe pain, a minimally invasive method is desirable. Gradual augmentation of flexion reflex and pain induced by repetitive stimulation of the sural nerve was observed using three stimulation methods—namely, bipolar electrical, magnetic, and monopolar electrical stimulation, with 11 healthy male subjects in each group. The effects of frequency, intensity, and number of repetitive stimuli on the increase in the magnitude of flexion reflex and pain rating were compared among the three methods. The reflex was measured using electromyography (EMG) from the short head of the biceps femoris. All three methods produced a frequency- and intensity-dependent progressive increase in reflex and pain; pain scores were significantly lower for magnetic and monopolar stimulations than for bipolar stimulation (P < 0.05). The slope of increase in the reflex was steep during the first 4–6 stimuli but became gentler thereafter. In the initial phase, an increase in the reflex during the time before signals of C-fibers arrived at the spinal cord was observed in experiments using high-frequency stimulation, suggesting that wind-up was caused by inputs of A-fibers without the involvement of C-fibers. Magnetic and monopolar stimulations are minimally invasive and useful methods for observing the wind-up of the flexion reflex in humans. Monopolar stimulation is convenient because it does not require special equipment. There is at least a partial mechanism underlying the wind-up of the flexion reflex that does not require C-fibers.

    DOI: 10.3389/fnins.2022.837340

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  9. 神経ブロックを併用した人工股関節置換術後に腓骨神経麻痺を呈し診断に苦慮した1例

    絹川 友章, 田村 高廣, 竹上 靖彦, 関 泰輔, 西脇 公俊

    日本ペインクリニック学会誌   28 巻 ( 9 ) 頁: 194 - 198   2021年9月

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    記述言語:日本語   出版者・発行元:一般社団法人 日本ペインクリニック学会  

    <p>【症例】46歳女性,身長157 cm,体重58 kg.20歳ごろより両股関節痛を生じ,変形性関節症と診断され保存的に加療していた.当院整形外科紹介受診し,左人工股関節置換術施行予定となった.腰神経叢ブロックと傍仙骨部の坐骨神経ブロックを施行後,全身麻酔導入し,手術を行った.術後のレントゲンで脚延長は20 mmであった.覚醒後,両下肢に運動障害と感覚障害があった.症状は数時間以内に改善し,腰神経叢ブロックが硬膜外ブロックになったと考えられ,画像検査で血種による神経圧迫などを除外した上で経過観察となった.その後,感覚障害と運動障害は改善傾向であったが左足関節の背屈運動のみ回復が遅れ,術28日後の筋電図検査にて腓骨頭レベルでの軽度腓骨神経障害と診断された.術32日後,杖歩行安定し退院した.【まとめ】本症例の神経症状は,腓骨頭レベルでの神経障害であることから,腓骨神経の過伸展等の物理的因子に起因することが推察されるが,腰神経叢ブロックが硬膜外ブロックになったことにより麻痺症状が初期段階ではマスクされた.また今回の神経ブロックが麻痺に影響した可能性も否定できない.</p>

    DOI: 10.11321/jjspc.21-0029

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  10. Test-retest reliability of prepulse inhibition paradigm using auditory evoked potentials

    Takeuchi Nobuyuki, Kinukawa Tomoaki, Sugiyama Shunsuke, Inui Koji, Nishihara Makoto

    NEUROSCIENCE RESEARCH   170 巻   頁: 187 - 194   2021年9月

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    記述言語:日本語   出版者・発行元:Neuroscience Research  

    Prepulse inhibition (PPI) is a neurological phenomenon in which a weak initial stimulus reduces the level of responses to a subsequent stronger stimulus. Although acoustic startle reflexes are usually used for PPI examinations, recent studies have observed similar phenomena with event-related cortical potentials. In the present study, test-retest reliability of PPI measured using auditory change-related cortical responses was assessed in 35 healthy adults. Four sound stimuli were randomly presented at an even probability; Standard, Test alone, Prepulse alone, and Test + Prepulse. The Standard stimulus was a train of 25-ms tone pulses at 70 dB for 650 ms, while for Test alone and Prepulse alone, the sound pressure was increased to 80 dB at 350 ms and 73 dB at 300 ms, respectively. Measurements were performed twice with at least 7 days separation, and validity was evaluated using intra-class correlation (ICC) for latency, amplitude, and suppression rate of the P50, N100, and P200 components. The results showed high ICC values for the latency and amplitude of nearly all components, except for response to Prepulse alone (0.3–0.6). Furthermore, ICC for suppression rate was greater than 0.5 for the peak-to-peak amplitude. Good reproducibility for N100 and P200 components was obtained with this method. The present results support the PPI paradigm as a reliable tool for clinical measurements of inhibitory functions.

    DOI: 10.1016/j.neures.2020.08.011

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  11. Conditioned Pain Modulation: Comparison of the Effects on Nociceptive and Non-nociceptive Blink Reflex

    Kinukawa Tomoaki Alex, Inui Koji, Taniguchi Tomoya, Takeuchi Nobuyuki, Sugiyama Shunsuke, Nishihara Makoto, Nishiwaki Kimitoshi, Kakigi Ryusuke

    NEUROSCIENCE   468 巻   頁: 168 - 175   2021年8月

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    記述言語:日本語   出版者・発行元:Neuroscience  

    Although conditioned pain modulation (CPM) is considered to represent descending pain inhibitory mechanisms triggered by noxious stimuli applied to a remote area, there have been no previous studies comparing CPM between pain and tactile systems. In this study, we compared CPM between the two systems objectively using blink reflexes. Intra-epidermal electrical stimulation (IES) and transcutaneous electrical stimulation (TS) were applied to the right skin area over the supraorbital foramen to evoke a nociceptive or a non-nociceptive blink reflex, respectively, in 15 healthy males. In the test session, IES or TS were applied six times and subjects reported the intensity of each stimulus on a numerical rating scale (NRS). Blink reflexes were measured using electromyography (R2). The first and second sessions were control sessions, while in the third session, the left hand was immersed in cold water at 10 °C as a conditioning stimulus. The magnitude of the R2 blink and NRS scores were compared among the sessions by 2-way ANOVA. Both the NRS score and nociceptive R2 were significantly decreased in the third session for IES, with a significant correlation between the two variables; whereas, TS-induced non-nociceptive R2 did not change among the sessions. Although the conditioning stimulus decreased the NRS score for TS, the CPM effect was significantly smaller than that for IES (p = 0.002). The present findings suggest the presence of a pain-specific CPM effect to a heterotopic noxious stimulus.

    DOI: 10.1016/j.neuroscience.2021.06.019

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  12. Test-retest reliability of paired pulse suppression paradigm using auditory change-related response

    Takeuchi Nobuyuki, Fujita Kohei, Kinukawa Tomoaki, Sugiyama Shunsuke, Kanemoto Kousuke, Nishihara Makoto, Inui Koji

    JOURNAL OF NEUROSCIENCE METHODS   352 巻   頁: 109087   2021年3月

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    記述言語:日本語   出版者・発行元:Journal of Neuroscience Methods  

    Background: Sensory suppression is an important brain function for appropriate processing of information and is known to be impaired in patients with various types of mental illness. Long latency suppression which is a paradigm using change-related cortical response with repeated paired pulses embedded in a train of conditioning pulses is a factor used to measure sensory suppression. New method: The present study assessed the test-retest reliability of long-latency suppression in latency, amplitude, and suppression rate of the P50, N100, and P200 components of auditory evoked potentials in 35 healthy adults. The sound stimulus was repeats of a 25-ms pure tone at 65 dB and 2000 ms in total duration, during which the sound pressure level was increased to 80 dB twice at 1100 ms and 1700 ms. Measurements were performed twice and the validity of the findings was evaluated using intra-class correlations. Results: The results showed high intra-class correlation (ICC) values (>0.7) for the amplitude of all components, except for P50 (0.44), while latency also showed high ICC values (>0.66), except for P50 (0.20). In addition, the suppression rate showed good reproducibility for the N100-P200 component (0.60). Comparison with Existing Method: The method can be performed with a short inspection time of approximately 5 min and provides high ICC values. In addition, it may reflect suppression mechanisms different from those relating to existing methods. Conclusion: These results support the use of long latency suppression as a biomarker in clinical settings.

    DOI: 10.1016/j.jneumeth.2021.109087

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  13. The Auditory Steady-State Response: Electrophysiological Index for Sensory Processing Dysfunction in Psychiatric Disorders

    Sugiyama Shunsuke, Ohi Kazutaka, Kuramitsu Ayumi, Takai Kentaro, Muto Yukimasa, Taniguchi Tomoya, Kinukawa Tomoaki, Takeuchi Nobuyuki, Motomura Eishi, Nishihara Makoto, Shioiri Toshiki, Inui Koji

    FRONTIERS IN PSYCHIATRY   12 巻   頁: 644541   2021年3月

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    記述言語:日本語   出版者・発行元:Frontiers in Psychiatry  

    Sensory processing is disrupted in several psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. In this review, we focus on the electrophysiological auditory steady-state response (ASSR) driven by high-frequency stimulus trains as an index for disease-associated sensory processing deficits. The ASSR amplitude is suppressed within the gamma band (≥30 Hz) among these patients, suggesting an imbalance between GABAergic and N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. The reduced power and synchronization of the 40-Hz ASSR are robust in patients with schizophrenia. In recent years, similar ASSR deficits at gamma frequencies have also been reported in patients with bipolar disorder and autism spectrum disorder. We summarize ASSR abnormalities in each of these psychiatric disorders and suggest that the observed commonalities reflect shared pathophysiological mechanisms. We reviewed studies on phase resetting in which a salient sensory stimulus affects ASSR. Phase resetting induces the reduction of both the amplitude and phase of ASSR. Moreover, phase resetting is also affected by rare auditory stimulus patterns or superimposed stimuli of other modalities. Thus, sensory memory and multisensory integration can be investigated using phase resetting of ASSR. Here, we propose that ASSR amplitude, phase, and resetting responses are sensitive indices for investigating sensory processing dysfunction in psychiatric disorders.

    DOI: 10.3389/fpsyt.2021.644541

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  14. Assessment of haptic memory using somatosensory change-related cortical responses

    Sugiyama Shunsuke, Kinukawa Tomoaki, Takeuchi Nobuyuki, Nishihara Makoto, Shioiri Toshiki, Inui Koji

    HUMAN BRAIN MAPPING   41 巻 ( 17 ) 頁: 4892 - 4900   2020年12月

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    記述言語:日本語   出版者・発行元:Human Brain Mapping  

    Haptic memory briefly retains somatosensory information for later use; however, how and which cortical areas are affected by haptic memory remain unclear. We used change-related cortical responses to investigate the relationship between the somatosensory cortex and haptic memory objectively. Electrical pulses, at 50 Hz with a duration of 500 ms, were randomly applied to the second, third, and fourth fingers of the right and left hands at an even probability every 800 ms. Each stimulus was labeled as D (preceded by a different side) or S (preceded by the same side). The D stimuli were further classified into 1D, 2D, and 3D, according to the number of different preceding stimuli. The S stimuli were similarly divided into 1S and 2S. The somatosensory-evoked magnetic fields obtained were divided into four components via a dipole analysis, and each component's amplitudes were measured using the source strength waveform. The results showed that the preceding event did not affect the amplitude of the earliest 20–30 ms response in the primary somatosensory cortex. However, in the subsequent three components, the cortical activity amplitude was largest in 3D, followed by 2D, 1D, and S. These results indicate that such modulatory effects occurred somewhere in the somatosensory processing pathway higher than Brodmann's area 3b. To the best of our knowledge, this is the first study to demonstrate the existence of haptic memory for somatosensory laterality and its impact on the somatosensory cortex using change-related cortical responses without contamination from peripheral effects.

    DOI: 10.1002/hbm.25165

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  15. Tactile Cross-Modal Acceleration Effects on Auditory Steady-State Response

    Sugiyama Shunsuke, Kinukawa Tomoaki, Takeuchi Nobuyuki, Nishihara Makoto, Shioiri Toshiki, Inui Koji

    FRONTIERS IN INTEGRATIVE NEUROSCIENCE   13 巻   頁: 72   2019年12月

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    記述言語:日本語   出版者・発行元:Frontiers in Integrative Neuroscience  

    In the sensory cortex, cross-modal interaction occurs during the early cortical stages of processing; however, its effect on the speed of neuronal activity remains unclear. In this study, we used magnetoencephalography (MEG) to investigate whether tactile stimulation influences auditory steady-state responses (ASSRs). To this end, a 0.5-ms electrical pulse was randomly presented to the dorsum of the left or right hand of 12 healthy volunteers at 700 ms while a train of 25-ms pure tones were applied to the left or right side at 75 dB for 1,200 ms. Peak latencies of 40-Hz ASSR were measured. Our results indicated that tactile stimulation significantly shortened subsequent ASSR latency. This cross-modal effect was observed from approximately 50 ms to 125 ms after the onset of tactile stimulation. The somatosensory information that appeared to converge on the auditory system may have arisen during the early processing stages, with the reduced ASSR latency indicating that a new sensory event from the cross-modal inputs served to increase the speed of ongoing sensory processing. Collectively, our findings indicate that ASSR latency changes are a sensitive index of accelerated processing.

    DOI: 10.3389/fnint.2019.00072

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  16. Change-Related Acceleration Effects on Auditory Steady State Response

    Sugiyama Shunsuke, Kinukawa Tomoaki, Takeuchi Nobuyuki, Nishihara Makoto, Shioiri Toshiki, Inui Koji

    FRONTIERS IN SYSTEMS NEUROSCIENCE   13 巻   頁: 53   2019年10月

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    記述言語:英語   出版者・発行元:Frontiers in Systems Neuroscience  

    Rapid detection of sensory changes is important for survival. We have previously used change-related cortical responses to study the change detection system and found that the generation of a change-related response was based on sensory memory and comparison processes. However, it remains unclear whether change-related cortical responses reflect processing speed. In the present study, we simultaneously recorded the auditory steady-state response (ASSR) and change-related response using magnetoencephalography to investigate the acceleration effects of sensory change events. Overall, 13 healthy human subjects (four females and nine males) completed an oddball paradigm with a sudden change in sound pressure used as the test stimulus, i.e., the control stimulus was a train of 25-ms pure tones at 75 dB for 1,200 ms, whereas the 29th sound at 700 ms of the test stimulus was replaced with a 90-dB tone. Thereafter, we compared the latency of ASSR among four probabilities of test stimulus (0, 25, 75, and 100%). For both the control and test stimulus, stronger effects of acceleration on ASSR were observed when the stimulus was rarer. This finding indicates that ASSR and change-related cortical response depend on physical changes as well as sensory memory and comparison processes. ASSR was modulated without changes in peripheral inputs, and brain areas higher than the primary cortex could be involved in exerting acceleration effects. Furthermore, the reduced latency of ASSR clearly indicated that a new sensory event increased the speed of ongoing sensory processing. Therefore, changes in the latency of ASSR are a sensitive index of accelerated processing.

    DOI: 10.3389/fnsys.2019.00053

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  17. Suppression of Somatosensory Evoked Cortical Responses by Noxious Stimuli

    Takeuchi Nobuyuki, Kinukawa Tomoaki, Sugiyama Shunsuke, Inui Koji, Kanemoto Kousuke, Nishihara Makoto

    BRAIN TOPOGRAPHY   32 巻 ( 5 ) 頁: 783 - 793   2019年9月

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    記述言語:日本語   出版者・発行元:Brain Topography  

    Paired-pulse suppression refers to attenuation of neural activity in response to a second stimulus and has a pivotal role in inhibition of redundant sensory inputs. Previous studies have suggested that cortical responses to a somatosensory stimulus are modulated not only by a preceding same stimulus, but also by stimulus from a different submodality. Using magnetoencephalography, we examined somatosensory suppression induced by three different conditioning stimuli. The test stimulus was a train of electrical pulses to the dorsum of the left hand at 100 Hz lasting 1500 ms. For the pulse train, the intensity of the stimulus was abruptly increased at 1200 ms. Cortical responses to the abrupt intensity change were recorded and used as the test response. Conditioning stimuli were presented at 600 ms as pure tones, either innocuous or noxious electrical stimulation to the right foot. Four stimulus conditions were used: (1) Test alone, (2) Test + auditory stimulus, (3) Test + somatosensory stimulus, and (4) Test + nociceptive stimulus. Our results showed that the amplitude of the test response was significantly smaller for conditions (3) and (4) in the secondary somatosensory cortex contralateral (cSII) and ipsilateral (iSII) to the stimulated side as compared to the response to condition (1), whereas the amplitude of the response in the primary somatosensory cortex did not differ among the conditions. The auditory stimulus did not have effects on somatosensory change-related response. These findings show that somatosensory suppression was induced by not only a conditioning stimulus of the same somatosensory submodality and the same cutaneous site to the test stimulus, but also by that of a different submodality in a remote area.

    DOI: 10.1007/s10548-019-00721-z

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科研費 1

  1. 電気生理学的手法を用いた内因性疼痛抑制能の測定法の確立

    研究課題/研究課題番号:21K16558  2021年4月 - 2025年3月

    日本学術振興会  科学研究費助成事業  若手研究

    絹川 友章

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    担当区分:研究代表者 

    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    皮膚侵害受容器を選択的に刺激する表皮内電気刺激法と、瞬目反射を用いることにより、客観的CPM測定法の確立を目指す。表皮内電気刺激法はコントロールが容易な侵害刺激法であり、現在のところレーザーを除いて唯一の選択的痛覚刺激法である。申請者はこの手法の開発者である乾博士(愛知県医療療育総合センター 発達障害研究所 障害システム研究部門)と現在共同研究をすすめており、本申請については、すでにパイロット実験を行っている。瞬目反射は当然意識外の事象であり、客観的なものである。これにより、簡便かつ客観性に富んだ、実臨床に応用できるCPM測定ができると期待される。
    CPM効果は侵害刺激から遠隔部位に条件刺激として温冷刺激を与えると、侵害刺激による主観的疼痛レベルが低下する現象である。CPM効果の低下と慢性痛(繊維筋痛症、変形性関節症、頭痛、過敏性腸症候群等)と周術期における術後遷延痛には関連があることが報告されており、臨床的に重要な検査となりつつある。
    現行のCPM測定法では特殊な圧刺激装置を使用することや、2週間に渡って2回測定する必要があるなど、実臨床に用いるには課題がある。しかし最も重要な問題は、加える刺激が特異的侵害刺激ではないことと、評価するのが主観的痛みのみであることである。そのため、簡便かつ客観性に優れた痛覚特異的CPM測定の方法の確立が望まれていた。
    今回、我々は侵害受容刺激に表皮内電気刺激法(Intra-Epidermal Stimulation:IES)を用い、評価法として主観的痛みに合わせて瞬目反射(BlinkRefelex)を用いることで、客観的に評価できる測定法を確立した。IESはコントールが用意で携行性に富んでおり、選択的に痛覚のみ刺激できる。また瞬目反射は脳幹反射であり随意に影響されない。瞬目反射における筋電図のR2成分を積算し、CPM効果の指標とした。本研究のパラダイムでは計3セッションで行っているが、条件刺激の有るセッションとないセッション、合計2セッションで施行しても再現性に問題なく、この場合1人の被験者あたりの測定には10分程度で完了できる。
    さらにCPM効果の新たな測定法を確立しただけでなく、CPM効果の触覚における発現についても評価を行った。触覚においても、痛覚同様CPM効果は発現するが、両者を比較すると、痛覚に有意に強く発現する現象と判明した。このことは、従来提唱されていたDNIC(diffuse noxious inhibitory controls)の概念と矛盾しない。
    CPM測定の客観的かつ簡便な計測方法を確立した。手法としては表皮内電気刺激法を用いることで痛覚刺激に客観性を持たせ、疼痛指標としては従来の主観的痛みだけでなく、瞬目反射の筋電図を計測することで客観性を担保した。パラダイムとしては、コントロール1,2セッション目とテスト刺激のある3セッション目で、合計3セッションとしたが、1,2セッション目に解析上データに有意差はなかったので、コントロール1セッション目、テスト刺激のある2セッション目として、合計2セッションで評価できると判明した。この場合、評価に合計10分程度だれば完了できる。また、CPM現象における、痛覚刺激、触覚刺激における発現の仕方についても調査を行い、このCPM現象が痛覚刺激、触覚刺激ともに発現するものの、痛覚刺激に対して有意に強く発現することも解明した。
    疼痛学の分野では、近年カプサイシンについて盛んに研究が行われている。
    カプサイシンはTRPV1チャネルを活性化することで灼熱痛を生じる。一方でカプサイシンの刺激が繰り返されるとTRPV1チャネルを介して細胞内に流入したカルシウムイオンにより、TRPV1チャネルが脱感作し、かえって痛覚鈍麻を生じるとされている。北米ではカプサイシンクリームが鎮痛剤として承認・発売され、臨床使用されている。ただし、カプサイシンクリームの効果については議論の的となっており、低濃度のカプサイシンクリームについては鎮痛効果は否定的な意見が多い。一方、高濃度となると、カプサイシンの全身作用により、消化器症状や高血圧症、流涙、鼻汁等の様々な問題が生じる。
    本研究にて確立したCPM測定法で、カプサイシンクリームを条件刺激に組み込み、カプサイシンの鎮痛効果の有無と、鎮痛効果を得るための至適濃度について今後、調査・研究することを検討している。