Updated on 2024/02/02

写真a

 
KURABE Miyuki
 
Organization
Academic Assembly Institute of Medicine and Dentistry IGAKU KEIRETU Assistant Professor
Graduate School of Medical and Dental Sciences Biological Functions and Medical Control Cardiovascular and Vital Control Assistant Professor
Title
Assistant Professor
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Degree

  • 学士(医学) ( 2007.3   新潟大学 )

Research Interests

  • 全身麻酔薬

Research Areas

  • Life Science / Neuroscience-general

Research History (researchmap)

  • 新潟大学医歯学総合研究科   生体機能調節医学専攻 器官制御医学   助教

    2019.4

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Research History

  • Niigata University   Graduate School of Medical and Dental Sciences Biological Functions and Medical Control Cardiovascular and Vital Control   Assistant Professor

    2019.4

  • Niigata University   University Medical and Dental Hospital Anesthesiology   Assistant Professor

    2017.3 - 2019.3

  • Niigata University   University Medical and Dental Hospital Anesthesiology   Specially Appointed Assistant Professor

    2016.2 - 2017.2

 

Papers

  • Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord. Reviewed International journal

    Yuka Nakamura, Miyuki Kurabe, Mami Matsumoto, Tokiharu Sato, Satoshi Miytashita, Kana Hoshina, Yoshinori Kamiya, Kazuki Tainaka, Hitoshi Matsuzawa, Nobuhiko Ohno, Masaki Ueno

    eLife   12   2023.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lying along the central canal of the spinal cord. Recent studies in zebrafish larvae and lampreys have shown that CSF-cNs control postures and movements via spinal connections. However, the structures, connectivity, and functions in mammals remain largely unknown. Here we developed a method to genetically target mouse CSF-cNs that highlighted structural connections and functions. We first found that intracerebroventricular injection of adeno-associated virus with a neuron-specific promoter and Pkd2l1-Cre mice specifically labeled CSF-cNs. Single-cell labeling of 71 CSF-cNs revealed rostral axon extensions of over 1800 μm in unmyelinated bundles in the ventral funiculus and terminated on CSF-cNs to form a recurrent circuitry, which was further determined by serial electron microscopy and electrophysiology. CSF-cNs were also found to connect with axial motor neurons and premotor interneurons around the central canal and within the axon bundles. Chemogenetic CSF-cNs inactivation reduced speed and step frequency during treadmill locomotion. Our data revealed the basic structures and connections of mouse CSF-cNs to control spinal motor circuits for proper locomotion. The versatile methods developed in this study will contribute to further understanding of CSF-cN functions in mammals.

    DOI: 10.7554/eLife.83108

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  • Structural and functional properties of spinal dorsal horn neurons after peripheral nerve injury change overtime via astrocyte activation Reviewed

    Miyuki Kurabe, Mika Sasaki, Kenta Furutani, Hidemasa Furue, Yoshinori Kamiya, Hiroshi Baba

    iScience   25 ( 12 )   105555 - 105555   2022.12

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    Authorship:Lead author, Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.isci.2022.105555

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  • A mechanism of re-sedation caused by remimazolam. Reviewed

    Tomohiro Yamamoto, Miyuki Kurabe, Yoshinori Kamiya

    Journal of anesthesia   35 ( 3 )   467 - 468   2021.6

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  • Re-sleeping after reversal of remimazolam by flumazenil. Reviewed

    Tomohiro Yamamoto, Miyuki Kurabe, Yoshinori Kamiya

    Journal of anesthesia   35 ( 2 )   322 - 322   2021.4

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  • Serotonin plays a key role in the development of opioid-induced hyperalgesia in mice. Reviewed International journal

    Mika Sasaki, Yoshinori Kamiya, Keiko Bamba, Takeshi Onishi, Keiichiro Matsuda, Tatsuro Kohno, Miyuki Kurabe, Kenta Furutani, Harue Yanagimura

    The journal of pain   22 ( 6 )   715 - 729   2021.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    Opioid usage for pain therapy is limited by its undesirable clinical effects, including paradoxical hyperalgesia, also known as opioid-induced hyperalgesia, (OIH). However, the mechanisms associated with the development and maintenance of OIH remain unclear. Here, we investigated the effect of serotonin inhibition by the 5-HT3 receptor antagonist, ondansetron (OND), as well as serotonin deprivation via its synthesis inhibitor para-chlorophenylalanine (PCPA), on mouse OIH models, with particular focus on astrocyte activation. Co-administering of OND and morphine, in combination with serotonin depletion, inhibited mechanical hyperalgesia and astrocyte activation in the spinal dorsal horn of mouse OIH models. Although previous studies have suggested that activation of astrocytes in the spinal dorsal horn is essential for the development and maintenance of OIH, herein, treatment with carbenoxolone (CBX), a gap junction inhibitor that suppresses astrocyte activation, did not ameliorate mechanical hyperalgesia in mouse OIH models. These results indicate that serotonin in the spinal dorsal horn, and activation of the 5-HT3 receptor play essential roles in OIH induced by chronic morphine, while astrocyte activation in the spinal dorsal horn serves as a secondary effect of OIH. Our findings further suggest that serotonergic regulation in the spinal dorsal horn may be a therapeutic target of OIH. PERSPECTIVE: The current study revealed that the descending serotonergic pain-facilitatory system in the spinal dorsal horn is crucial in OIH, and that activation of astrocytes is a secondary phenotype of OIH. Our study offers new therapeutic targets for OIH and may help reduce inappropriate opioid use.

    DOI: 10.1016/j.jpain.2020.12.008

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  • Congenital Tracheal Aplasia Without Prenatal Diagnosis Masked by Maternal Obesity and Gestational Diabetes: A Case Report. Reviewed International journal

    Tomohiro Yamamoto, Miyuki Kurabe, Kensuke Matsumoto, Shunya Sugai, Hiroshi Baba

    A&A practice   14 ( 6 )   e01200   2020.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    This case report describes a neonate with tracheal aplasia first diagnosed after birth due to the presentation of respiratory distress, absence of crying, and unsuccessful tracheal intubation. The most common finding with tracheal aplasia is polyhydramnios. However, diagnosis remains challenging in the prenatal period. In this case, maternal obesity and gestational diabetes made diagnosis more difficult. The only lifesaving treatment available is ventilation through esophageal intubation or tracheostomy. However, in some cases, tracheostomy is not an option.

    DOI: 10.1213/XAA.0000000000001200

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  • Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis (vol 6, 26253, 2016) Reviewed

    Miyuki Kurabe, Hidemasa Furue, Tatsuro Kohno

    SCIENTIFIC REPORTS   7   46814   2017.6

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    Authorship:Lead author   Language:English   Publisher:NATURE PUBLISHING GROUP  

    DOI: 10.1038/srep46814

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  • Perforation of the superior vena cava 5 days after insertion of a central venous catheter through the left internal jugular vein Reviewed

    Miyuki Kurabe, Tatsunori Watanabe, Tatsuro Kohno

    JOURNAL OF CLINICAL ANESTHESIA   31   193 - 196   2016.6

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    Authorship:Lead author   Language:English   Publisher:ELSEVIER SCIENCE INC  

    We describe a very rare case of an indwelling central venous catheter (CVC) through the left internal jugular vein that perforated the superior vena cava (SVC) wall postoperatively, although the CVC was placed in the appropriate position preoperatively. Three days after CVC insertion, a chest radiograph showed that the CVC tip had moved from the lower SVC to the upper SVC. Five days after the insertion, computed tomography showed SVC perforation and the resulting hydrothorax. In cases of CVC insertion through the left side, the CVC tip should not be placed in the upper SVC (zone B). Considering individual clinical factors and the indwelling period for the CVC, the left innominate vein (zone C) may be a suitable site for the left-sided CVC tip to reduce the risk of SVC perforation. (C) 2016 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.jclinane.2016.02.002

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  • Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis Reviewed

    Miyuki Kurabe, Hidemasa Furue, Tatsuro Kohno

    SCIENTIFIC REPORTS   6   26253   2016.5

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:NATURE PUBLISHING GROUP  

    Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain.

    DOI: 10.1038/srep26253

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  • トラネキサム酸の脊髄後角における抑制性シナプス伝達に対する作用

    大橋 宣子, 佐々木 美佳, 山本 豪, 倉部 美起, 古谷 健太, 大橋 正幸, 紙谷 義孝, 馬場 洋, 河野 達郎

    脊髄機能診断学   35 ( 1 )   52 - 57   2015.1

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    Language:Japanese   Publisher:エーザイ(株)  

    トラネキサム酸(TXA)の痛みに対する作用・機序について検討するため、まずラットを用いて行動学実験を行った。クモ膜下腔に留置したカテーテルよりTXAを投与して自発痛様行動を観察した結果、その持続時間は濃度依存性に延長した。次に電気生理学的実験として、脊髄後角膠様質細胞を用いてホールセルパッチクランプ記録を行い、TXAの灌流投与に対する自発性抑制性シナプス後電流(sIPSC)の反応を調べた。sIPSCの振幅はTXA投与により減少し、頻度は変化がなかった。またグリシン受容体拮抗薬のstrychnineまたはガンマアミノ酪酸(GABA)受容体拮抗薬のbicucullineを灌流投与したところ、strychnine存在下ではGABA作動性sIPSC、bicuculline存在下ではグリシン作動性sIPSCの振幅は減少した。TXAは脊髄後角ニューロンのGABAおよびグリシン受容体をシナプス後性に抑制し、それによって自発痛を増強させる可能性が示唆された。

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Books

  • 痛みの薬物治療 (痛みのScience & Practice)

    山本 達郎

    文光堂  2013.7  ( ISBN:4830628340

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    Total pages:322  

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MISC

  • Intravenous administration of lidocaine inhibits excitatory synaptic transmission in spinal dorsal horn neurons

    倉部 美起, 大橋 宣子, 山本 豪

    脊髄機能診断学   35 ( 1 )   46 - 51   2014

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    Language:Japanese   Publisher:エーザイ  

    CiNii Article

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  • 4 消化器手術後のC. diffidile腸炎の検討(II.主題,第59回新潟大腸肛門病研究会)

    倉部 美起, 酒井 靖夫, 坪野 俊広, 武者 信行, 田邊 匡, 桑原 明史, 角田 和彦

    新潟医学会雑誌   122 ( 7 )   390 - 390   2008.7

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    Language:Japanese   Publisher:新潟医学会  

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Research Projects

  • Manipulating Descending Pain Suppression Systems Using Chemogenetics to Find Seeds for Chronic Pain Treatment

    Grant number:22H03167

    2022.4 - 2026.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\16510000 ( Direct Cost: \12700000 、 Indirect Cost:\3810000 )

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  • 光遺伝学を利用した青斑核ニューロン制御による全身麻酔薬作用機序の解明

    Grant number:21K08943

    2021.4 - 2024.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    倉部 美起, 佐々木 美佳, 上野 将紀

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    全身麻酔薬の作用機序は現代においても未解明である。睡眠・覚醒と密接な関わりを持つ、“青斑核”を起始核とするノルアドレナリン(NA)ニューロンが全身麻酔時の意識消失や覚醒にも関与していると考えられているが、詳細は不明である。近年、青斑核ニューロンが一様ではなく、NAニューロン以外にGABA(gamma-Aminobutyric acid)ニューロンを含み、相互作用していることが明らかになったことから、GABAニューロンとNAニューロンとの相互の関係性が、全身麻酔薬の作用機序に大きく関与しているのではないかと考えた。そこで、全身麻酔時の青斑核NA/GABAニューロンの活動が果たす機能的役割とそれぞれの神経の相互関連性を、光遺伝学的手法を用いて解明することを目的とした。
    初年度は光遺伝学的手法の導入と確認を組織学的・生理学的両面から行った。青斑核NAニューロンを特異的に操作するために、NAニューロン特異的プロモーターPRSx8下でチャネルロドプシン・アーキロドプシンを発現するアデノ随伴ウイルスを作製し、C57BL/6マウス青斑核に脳定位固定装置を用いて投与した。免疫組織学的に、青斑核ニューロンに特異的に発現することを確認した。さらにこれらのマウスから青斑核スライス標本を作製し近赤外線
    微分干渉顕微鏡を用いて可視下にホールセルパッチクランプ記録を行った。NAニューロンは電流固定モード下で3~4Hzの活動電位を発していた。また、光刺激によって活動電位の発火頻度が増加あるいは減少することを確認した。
    これらの結果を基に、次年度はNA/GABAニューロン制御下に電気生理学解析を進め、無麻酔状態のマウスからの脳波・行動解析を行う予定である。

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  • Why does neuropathic pain spread beyond the area of control of the injured peripheral nerves?

    Grant number:20H03775

    2020.4 - 2023.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\10660000 ( Direct Cost: \8200000 、 Indirect Cost:\2460000 )

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  • Elucidating mechanisms of action of general anesthetics using chemogenetics

    Grant number:19K22652

    2019.6 - 2021.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Challenging Research (Exploratory)

    Awarding organization:Japan Society for the Promotion of Science

    Kamiya Yoshinori

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    Grant amount:\6240000 ( Direct Cost: \4800000 、 Indirect Cost:\1440000 )

    The purpose of this study was to use chemogenetics to manipulate noradrenergic (NA) neurons in the locus coeruleus to determine the role of NA neurons in the loss of consciousness and arousal during general anesthesia. To specifically manipulate the NA neurons, an adeno-associated virus (AAV1-PRSx8-hM3Dq-HA) was prepared and injected into the rat locus coeruleus. NA neuron activation only slightly altered the induction and arousal times of volatile anesthetics, but markedly altered the induction and arousal times of intravenous anesthetics. Furthermore, we established a method for electrophysiological analysis under free moving and under the control of the NA neurons

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  • Brain-Spinal Cord Plasticity Changes during the Establishment of Chronic Pain: Elucidation of the Role of Inhibitory Neural Circuits

    Grant number:18K08811

    2018.4 - 2021.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    Miyuki Kurabe

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    We hypothesized that not only hyperexcitability of excitatory neurotransmission but also hyperexcitability of inhibitory neuronal circuits may be involved in the synaptic plasticity changes that develop during the establishment of chronic pain. We aimed to elucidate the role of inhibitory circuits in spinal plasticity from the early stage of peripheral nerve injury to the establishment of chronic pain, focusing especially on the descending inhibitory system.
    Using the DREADD system, we selectively activated neurons in locus coeruleus, one of the originating nuclei of the descending inhibitory system, and analyzed their effects on pain responses. In addition to the in vivo patch-clamp method, behavioral and immunohistological analyses were also performed to conduct an integrated study to elucidate the role of the descending inhibitory system in pain.

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  • Physiological analysis of spinal cord-brain coupling in neuropathic pain and elucidation of glial cell activation mechanism.

    Grant number:18H02897

    2018.4 - 2021.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    Kamiya Yoshinori

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    Grant amount:\15730000 ( Direct Cost: \12100000 、 Indirect Cost:\3630000 )

    In this study, physiological changes in neuronal excitation in the spinal dorsal horn, the relay point of perception, and in the primary sensory cortex, the endpoint of perception, were measured longitudinally after peripheral nerve injury using flavoprotein fluorescence imaging and in vivo patch-clamp techniques. Although pain thresholds were consistently lowered after peripheral nerve injury, excitation in the cerebral cortex increased over time, while excitation in the spinal cord tended to decrease. The patch-clamp technique revealed that excitatory and inhibitory synaptic transmission in the spinal cord changes dynamically over time. The changes in synaptic transmission in the dorsal horn of the spinal cord could be suppressed by astrocyte inhibition, but astrocyte inhibition was ineffective in different chronic pain models.

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  • Contribution of glycinnergic neurons to spinal plasticity in neuropathic pain

    Grant number:16K20083

    2016.4 - 2018.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Research category:Grant-in-Aid for Young Scientists (B)

    Awarding organization:Japan Society for the Promotion of Science

    KUEABE MIYUKI

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    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

    Little is known about the role of glycineergic neuron of spinal dorsal horn in neuropathic pain. We analyzed changes of inhibitory neuronal transmission between normal rats and neuropathic pain model rats using in vivo patch-clamp technique. As a result, only the amplitude of the inhibitory postsynaptic current decreased. There was no difference in the frequency and amplitude of glycineergic IPSC between the two groups. Furthermore, in model rats relative GABAergic neurons increased. The balance changes of these inhibitory neurons were thought to play a part of plasticity change in neuropathic pain.

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  • Underlying mechanisms of intravenous administration of lidocaine in spinal dorsal horn

    Grant number:25861365

    2013.4 - 2015.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Research category:Grant-in-Aid for Young Scientists (B)

    Awarding organization:Japan Society for the Promotion of Science

    KURABE Miyuki

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    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

    Intravenous administration of lidocaine (IVL) is used for the management of postoperative and neuropathic pain. However, the analgesic mechanisms of IVL are yet to be elucidated. We hypothesized that IVL may affect excitatory synaptic transmission in spinal dorsal horn neurons. Herein, we used in vivo patch-clamp recording to examine the effects of IVL on synaptic transmission in the dorsal horn neurons of adult male Wistar rats. The experiments were performed in the voltage-clamp mode at a holding potential of -70 mV. IVL (3 and 10 mg/kg) decreased sEPSC frequencies, but did not affect the amplitudes. IVL (10 mg/kg) also decreased the area under the curve of EPSCs evoked by peripheral pinch stimuli to the receptive field. However IVL, superfusion of lidocaine (100 μM) on the spinal surface did not affect sEPSC frequencies or amplitudes. Our results suggest that IVL inhibits excitatory synaptic transmission in spinal dorsal horn neurons, which may be one of the analgesic mechanisms.

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