Updated on 2025/10/17

写真a

 
UCHIDA Hitoshi
 
Organization
Brain Research Institute Assistant Professor
Title
Assistant Professor
External link

Degree

  • 博士（薬学） ( 2009.3   長崎大学 )

Research Interests

  • イメージング

  • 一次知覚神経

  • エピジェネティクス

  • RNA編集

  • 痛み

  • 痒み

  • 組織透明化

Research Areas

  • Life Science / Neuroscience-general

Research History

  • Niigata University   Brain Research Institute Basic Neuroscience Branch Department of Cellular Neurobiology   Assistant Professor

    2015.3

Professional Memberships

Committee Memberships

  • 日本薬理学会   学術評議員  

    2015.4   

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    Committee type：Academic society

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Papers

  • descSPIM: an affordable and easy-to-build light-sheet microscope optimized for tissue clearing techniques. International journal

    Kohei Otomo, Takaki Omura, Yuki Nozawa, Steven J Edwards, Yukihiko Sato, Yuri Saito, Shigehiro Yagishita, Hitoshi Uchida, Yuki Watakabe, Kiyotada Naitou, Rin Yanai, Naruhiko Sahara, Satoshi Takagi, Ryohei Katayama, Yusuke Iwata, Toshiro Shiokawa, Yoku Hayakawa, Kensuke Otsuka, Haruko Watanabe-Takano, Yuka Haneda, Shigetomo Fukuhara, Miku Fujiwara, Takenobu Nii, Chikara Meno, Naoki Takeshita, Kenta Yashiro, Juan Marcelo Rosales Rocabado, Masaru Kaku, Tatsuya Yamada, Yumiko Oishi, Hiroyuki Koike, Yinglan Cheng, Keisuke Sekine, Jun-Ichiro Koga, Kaori Sugiyama, Kenichi Kimura, Fuyuki Karube, Hyeree Kim, Ichiro Manabe, Tomomi Nemoto, Kazuki Tainaka, Akinobu Hamada, Hjalmar Brismar, Etsuo A Susaki

    Nature communications   15 ( 1 )   4941 - 4941   2024.6

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

    Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM for cleared specimens), a low-cost ($20,000-50,000), low-expertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a three-dimensional manner. Academically open-sourced ( https://github.com/dbsb-juntendo/descSPIM ), descSPIM allows routine three-dimensional imaging of cleared samples in minutes. Thus, the dissemination of descSPIM will accelerate biomedical discoveries driven by tissue clearing technologies.

    DOI： 10.1038/s41467-024-49131-1

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  • Brn3a controls the soma localization and axonal extension patterns of developing spinal dorsal horn neurons Reviewed

    Kazuhiko Nishida, Shinji Matsumura, Hitoshi Uchida, Manabu Abe, Kenji Sakimura, Tudor Constantin Badea, Takuya Kobayashi

    PLOS ONE   18 ( 9 )   e0285295 - e0285295   2023.9

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    Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

    The spinal dorsal horn comprises heterogeneous neuronal populations, that interconnect with one another to form neural circuits modulating various types of sensory information. Decades of evidence has revealed that transcription factors expressed in each neuronal progenitor subclass play pivotal roles in the cell fate specification of spinal dorsal horn neurons. However, the development of subtypes of these neurons is not fully understood in more detail as yet and warrants the investigation of additional transcription factors. In the present study, we examined the involvement of the POU domain-containing transcription factor Brn3a in the development of spinal dorsal horn neurons. Analyses of Brn3a expression in the developing spinal dorsal horn neurons in mice demonstrated that the majority of the Brn3a-lineage neurons ceased Brn3a expression during embryonic stages (Brn3a-transient neurons), whereas a limited population of them continued to express Brn3a at high levels after E18.5 (Brn3a-persistent neurons). Loss of Brn3a disrupted the localization pattern of Brn3a-persistent neurons, indicating a critical role of this transcription factor in the development of these neurons. In contrast, Brn3a overexpression in Brn3a-transient neurons directed their localization in a manner similar to that in Brn3a-persistent neurons. Moreover, Brn3a-overexpressing neurons exhibited increased axonal extension to the ventral and ventrolateral funiculi, where the axonal tracts of Brn3a-persistent neurons reside. These results suggest that Brn3a controls the soma localization and axonal extension patterns of Brn3a-persistent spinal dorsal horn neurons.

    DOI： 10.1371/journal.pone.0285295

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  • Receptor Transporter Protein 4 (RTP4) in the Hypothalamus Is Involved in the Development of Antinociceptive Tolerance to Morphine

    Wakako Fujita, Hitoshi Uchida, Masashi Kawanishi, Yusuke Kuroiwa, Manabu Abe, Kenji Sakimura

    Biomolecules   12 ( 10 )   1471 - 1471   2022.10

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    Receptor transporter protein 4 (RTP4), one of the receptor chaperone proteins, contributes to the maturation and membrane trafficking of opioid receptor heteromers consisting of mu (MOPr) and delta (DOPr) opioid receptors (MOPr-DOPr). Although MOPr-DOPr is known to mediate the development of morphine tolerance, the extent to which RTP4 plays a role in this process has not been elucidated. Given that RTP4 can be upregulated by repeated administration of morphine, especially in the hypothalamus, here we investigated the effect of hypothalamus-selective ablation of RTP4 on the development of antinociceptive tolerance to morphine. In this study, we generated RTP4flox mice and selectively knocked-out RTP4 using local injection of adeno-associated virus expressing Cre recombinase (AAV-Cre) into the hypothalamus. The AAV-Cre injection partially, but significantly, decreased the level of RTP4 expression, and suppressed the development of antinociceptive tolerance to morphine. Next, we examined the mechanism of regulation of RTP4 and found that, in neuronal cells, Rtp4 induction is via Gi and MAPK activation, while, in microglial cells, the induction is via Toll-like receptor 4. Together, these studies highlight the role of MOR activity in regulating RTP4, which, in turn, plays an important role in modulating morphine effects in vivo.

    DOI： 10.3390/biom12101471

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  • Allodynia by Splenocytes From Mice With Acid-Induced Fibromyalgia-Like Generalized Pain and Its Sexual Dimorphic Regulation by Brain Microglia. Reviewed International journal

    Hiroshi Ueda, Naoki Dozono, Keigo Tanaka, Shuji Kaneko, Hiroyuki Neyama, Hitoshi Uchida

    Frontiers in neuroscience   14   600166 - 600166   2020.12

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    Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

    Fibromyalgia (FM), a disease of unknown etiology characterized by chronic generalized pain, is partly recapitulated in an animal model induced by repeated acid saline injections into the gastrocnemius muscle. Here, we attempted to investigate the sex difference in pain hypersensitivity (mechanical allodynia and hypersensitivity to electrical stimulation) in the repeated acid saline-induced FM-like generalized pain (AcGP) model. The first unilateral acid injection into gastrocnemius muscle at day 0/D0 and second injection at D5 (post day 0, P0) induced transient and long-lasting mechanical allodynia, respectively, on both sides of male and female mice. The pretreatment with gonadectomy did not affect the first injection-induced allodynia in both sexes, but gradually reversed the second injection-induced allodynia in male but not female mice. Moreover, the AcGP in male mice was abolished by intracerebroventricular minocycline treatments during D4-P4 or P5-P11, but not by early treatments during D0-D5 in male but not female mice, suggesting that brain microglia are required for AcGP in late-onset and sex-dependent manners. We also found that the intravenous treatments of splenocytes derived from male but not female mice treated with AcGP caused allodynia in naive mice. In addition, the purified CD4+ T cells derived from splenocytes of acid-treated male mice retained the ability to cause allodynia in naive mice. These findings suggest that FM-like AcGP has multiple sexual dimorphic mechanisms.

    DOI： 10.3389/fnins.2020.600166

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  • Mirtazapine, an α2 antagonist-type antidepressant reverses pain and lack of morphine analgesia in fibromyalgia-like mouse models. Reviewed International journal

    Hiroyuki Neyama, Naoki Dozono, Hitoshi Uchida, Hiroshi Ueda

    The Journal of pharmacology and experimental therapeutics   375 ( 1 )   1 - 9   2020.10

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

    Treatment for fibromyalgia is an unmet medical need; however, its pathogenesis is still poorly understood. In a series of studies, we have demonstrated that some pharmacological treatments reverse generalized chronic pain, but do not affect the lack of morphine analgesia in the intermittent cold stress (ICS)-induced fibromyalgia-like pain model in mice. Here we report that repeated intraperitoneal treatments with mirtazapine (Mir), which is presumed to disinhibit 5-HT release and activate 5-HT1 receptor through mechanisms of blocking presynaptic adrenergic α2, postsynaptic 5-HT2 and 5-HT3 receptors, completely reversed the chronic pain for more than 4-5 days after the cessation of treatments. The repeated Mir-treatments also recovered the morphine analgesia after the return of nociceptive threshold to the normal level. The microinjection of siRNA adrenergic α2a receptor (ADRA2A) into the habenula, which showed a selective upregulation of α2 receptor gene expression after ICS, reversed the hyperalgesia, but did not recover the morphine analgesia. However, both reversal of hyperalgesia and recovery of morphine analgesia were observed when siRNA ADRA2A was administered intracebroventricularly. As the habenular is reported to be involved in the emotion/reward-related pain and hypoalgesia, these results suggest that Mir could attenuate pain and/or augment hypoalgesia by blocking the habenular α2 receptor after ICS. The recovery of morphine analgesia in the ICS model, on the other hand, seems to be mediated through a blockade of α2 receptor in unidentified brain regions. SIGNIFICANCE STATEMENT: This study reports possible mechanisms underlying the complete reversal of hyperalgesia and recovery of morphine analgesia by mirtazapine, a unique antidepressant with adrenergic α2 and serotonergic receptor antagonist properties, in a type of intermittently repeated stress (ICS)-induced fibromyalgia-like pain model. Habenula, a brain region which is related to the control of emotional pain, was found to play key roles in the anti-hyperalgesia, while other brain regions appeared to be involved in the recovery of morphine analgesia in the ICS-model.

    DOI： 10.1124/jpet.120.265942

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  • GRP receptor and AMPA receptor cooperatively regulate itch-responsive neurons in the spinal dorsal horn. Reviewed International journal

    Norikazu Kiguchi, Daisuke Uta, Huiping Ding, Hitoshi Uchida, Fumihiro Saika, Shinsuke Matsuzaki, Yohji Fukazawa, Manabu Abe, Kenji Sakimura, Mei-Chuan Ko, Shiroh Kishioka

    Neuropharmacology   170   108025 - 108025   2020.6

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    Gastrin-releasing peptide (GRP) receptor-expressing (GRPR)+ neurons have a central role in the spinal transmission of itch. Because their fundamental regulatory mechanisms are not yet understood, it is important to determine how such neurons are excited and integrate itch sensations. In this study, we investigated the mechanisms for the activation of itch-responsive GRPR+ neurons in the spinal dorsal horn (SDH). GRPR+ neurons expressed the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) containing the GluR2 subunit. In mice, peripherally elicited histaminergic and non-histaminergic itch was prevented by intrathecal (i.t.) administration of the AMPAR antagonist NBQX, which was consistent with the fact that firing of GRPR+ neurons in SDH under histaminergic and non-histaminergic itch was completely blocked by NBQX, but not by the GRPR antagonist RC-3095. Because GRP+ neurons in SDH contain glutamate, we investigated the role of GRP+ (GRP+/Glu+) neurons in regulating itch. Chemogenetic inhibition of GRP+ neurons suppressed both histaminergic and non-histaminergic itch without affecting the mechanical pain threshold. In nonhuman primates, i.t. administration of NBQX also attenuated peripherally elicited itch without affecting the thermal pain threshold. In a mouse model of diphenylcyclopropenone (DCP)-induced contact dermatitis, GRP, GRPR, and AMPAR subunits were upregulated in SDH. DCP-induced itch was prevented by either silencing GRP+ neurons or ablation of GRPR+ neurons. Altogether, these findings demonstrate that GRP and glutamate cooperatively regulate GRPR+ AMPAR+ neurons in SDH, mediating itch sensation. GRP-GRPR and the glutamate-AMPAR system may play pivotal roles in the spinal transmission of itch in rodents and nonhuman primates.

    DOI： 10.1016/j.neuropharm.2020.108025

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  • Two isoforms of cyclic GMP-dependent kinase-I exhibit distinct expression patterns in the adult mouse dorsal root ganglion. Reviewed

    Uchida H, Matsumura S, Katano T, Watanabe M, Schlossmann J, Ito S

    Molecular pain   14   1744806918796409   2018.1

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  • RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury Reviewed

    Hitoshi Uchida, Shinji Matsumura, Shunpei Okada, Tsutomu Suzuki, Toshiaki Minami, Seiji Ito

    FASEB JOURNAL   31 ( 5 )   1847 - 1855   2017.5

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    DOI： 10.1096/fj.201600950R

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  • Phosphorylation of NMDA receptor GluN2B subunit at Tyr1472 is important for trigeminal processing of itch Reviewed

    Akitoshi Inoue, Hitoshi Uchida, Takanobu Nakazawa, Tadashi Yamamoto, Seiji Ito

    EUROPEAN JOURNAL OF NEUROSCIENCE   44 ( 7 )   2474 - 2482   2016.10

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    DOI： 10.1111/ejn.13337

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  • Differential regulation of expression of RNA-editing enzymes, ADAR1 and ADAR2, by 5-aza-2 '-deoxycytidine and trichostatin A in human neuronal SH-SY5Y cells Reviewed

    Hitoshi Uchida, Seiji Ito

    NEUROREPORT   26 ( 18 )   1089 - 1094   2015.12

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    DOI： 10.1097/WNR.0000000000000474

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  • Histone deacetylase inhibitors relieve morphine resistance in neuropathic pain after peripheral nerve injury Reviewed

    Hitoshi Uchida, Yosuke Matsushita, Kohei Araki, Takehiro Mukae, Hiroshi Ueda

    JOURNAL OF PHARMACOLOGICAL SCIENCES   128 ( 4 )   208 - 211   2015.8

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    DOI： 10.1016/j.jphs.2015.07.040

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  • Donepezil Reverses Intermittent Stress-Induced Generalized Chronic Pain Syndrome in Mice Reviewed

    Takehiro Mukae, Hitoshi Uchida, Hiroshi Ueda

    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS   353 ( 3 )   471 - 479   2015.6

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    DOI： 10.1124/jpet.114.222414

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  • Epigenetic Modification in Neuropathic Pain Reviewed

    Hiroshi Ueda, Hitoshi Uchida

    CURRENT PHARMACEUTICAL DESIGN   21 ( 7 )   849 - 867   2015

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  • Lysophosphatidic acid and its receptors LPA(1) and LPA(3) mediate paclitaxel-induced neuropathic pain in mice Reviewed

    Hitoshi Uchida, Jun Nagai, Hiroshi Ueda

    MOLECULAR PAIN   10   71   2014.11

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

    DOI： 10.1186/1744-8069-10-71

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  • Identification of nitrated tyrosine residues of protein kinase G-I alpha by mass spectrometry Reviewed

    Jingshan Lu, Ikuko Yao, Masahito Shimojo, Tayo Katano, Hitoshi Uchida, Mitsutoshi Setou, Seiji Ito

    ANALYTICAL AND BIOANALYTICAL CHEMISTRY   406 ( 5 )   1387 - 1396   2014.2

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    DOI： 10.1007/s00216-013-7535-4

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  • EPIGENETIC REGULATION OF BDNF EXPRESSION IN THE PRIMARY SENSORY NEURONS AFTER PERIPHERAL NERVE INJURY: IMPLICATIONS IN THE DEVELOPMENT OF NEUROPATHIC PAIN Reviewed

    H. Uchida, Y. Matsushita, H. Ueda

    NEUROSCIENCE   240   147 - 154   2013.6

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    DOI： 10.1016/j.neuroscience.2013.02.053

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  • Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants Reviewed

    Michiko Nishiyori, Hitoshi Uchida, Jun Nagai, Kohei Araki, Takehiro Mukae, Shiroh Kishioka, Hiroshi Ueda

    MOLECULAR PAIN   7   69   2011.9

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    DOI： 10.1186/1744-8069-7-69

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  • Autotaxin and lysophosphatidic acid(1) receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine Reviewed

    Jun Nagai, Hitoshi Uchida, Yosuke Matsushita, Ryo Yano, Mutsumi Ueda, Masami Niwa, Junken Aoki, Jerold Chun, Hiroshi Ueda

    MOLECULAR PAIN   6   78   2010.11

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    DOI： 10.1186/1744-8069-6-78

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  • Endocrine disrupting chemicals bind to a novel receptor, microtubule-associated protein 2, and positively and negatively regulate dendritic outgrowth in hippocampal neurons Reviewed

    Hayato Matsunaga, Kaori Mizota, Hitoshi Uchida, Takafumi Uchida, Hiroshi Ueda

    JOURNAL OF NEUROCHEMISTRY   114 ( 5 )   1333 - 1343   2010.9

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    DOI： 10.1111/j.1471-4159.2010.06847.x

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  • Evidence for De Novo Synthesis of Lysophosphatidic Acid in the Spinal Cord through Phospholipase A(2) and Autotaxin in Nerve Injury-Induced Neuropathic Pain Reviewed

    Lin Ma, Hitoshi Uchida, Jun Nagai, Makoto Inoue, Junken Aoki, Hiroshi Ueda

    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS   333 ( 2 )   540 - 546   2010.5

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    DOI： 10.1124/jpet.109.164830

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  • Calpain-mediated down-regulation of myelin-associated glycoprotein in lysophosphatidic acid-induced neuropathic pain Reviewed

    Weijiao Xie, Hitoshi Uchida, Jun Nagai, Mutsumi Ueda, Jerold Chun, Hiroshi Ueda

    JOURNAL OF NEUROCHEMISTRY   113 ( 4 )   1002 - 1011   2010.5

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    DOI： 10.1111/j.1471-4159.2010.06664.x

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  • NEURON-RESTRICTIVE SILENCER FACTOR CAUSES EPIGENETIC SILENCING OF K(V)4.3 GENE AFTER PERIPHERAL NERVE INJURY Reviewed

    H. Uchida, K. Sasaki, L. Ma, H. Ueda

    NEUROSCIENCE   166 ( 1 )   1 - 4   2010.3

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    DOI： 10.1016/j.neuroscience.2009.12.021

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  • Epigenetic Gene Silencing Underlies C-Fiber Dysfunctions in Neuropathic Pain Reviewed

    Hitoshi Uchida, Lin Ma, Hiroshi Ueda

    JOURNAL OF NEUROSCIENCE   30 ( 13 )   4806 - 4814   2010.3

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    DOI： 10.1523/JNEUROSCI.5541-09.2010

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  • Prothymosin alpha as robustness molecule against ischemic stress to brain and retina Reviewed

    Hiroshi Ueda, Hayato Matsunaga, Hitoshi Uchida, Mutsumi Ueda

    THYMOSINS IN HEALTH AND DISEASE   1194   20 - 26   2010

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    DOI： 10.1111/j.1749-6632.2010.05466.x

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  • Lysophosphatidic acid-3 receptor-mediated feed-forward production of lysophosphatidic acid: an initiator of nerve injury-induced neuropathic pain Reviewed

    Lin Ma, Hitoshi Uchida, Jun Nagai, Makoto Inoue, Jerold Chun, Junken Aoki, Hiroshi Ueda

    MOLECULAR PAIN   5   64   2009.11

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    DOI： 10.1186/1744-8069-5-64

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  • Profiling of BoNT/C3-reversible gene expression induced by lysophosphatidic acid: ephrinB1 gene up-regulation underlying neuropathic hyperalgesia and allodynia Reviewed

    Hitoshi Uchida, Misaki Matsumoto, Hiroshi Ueda

    NEUROCHEMISTRY INTERNATIONAL   54 ( 3-4 )   215 - 221   2009.3

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    DOI： 10.1016/j.neuint.2008.11.004

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  • Novel type of G(q/11) protein-coupled neurosteroid receptor sensitive to endocrine disrupting chemicals in mast cell line (RBL-2H3) Reviewed

    K Mizota, A Yoshida, H Uchida, R Fujita, H Ueda

    BRITISH JOURNAL OF PHARMACOLOGY   145 ( 4 )   545 - 550   2005.6

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    DOI： 10.1038/sj.bjp.0706213

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  • Neurosteroid-induced hyperalgesia through a histamine release is inhibited by progesterone and p,p '-DDE, an endocrine disrupting chemical Reviewed

    H Uchida, K Mizuno, A Yoshida, H Ueda

    NEUROCHEMISTRY INTERNATIONAL   42 ( 5 )   401 - 407   2003.4

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    DOI： 10.1016/S0197-0186(02)00135-3

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  • Anatomical and physiological evidence for involvement of tuberoinfundibular peptide of 39 residues in nociception Reviewed

    A Dobolyi, H Ueda, H Uchida, M Palkovits, TB Usdin

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   99 ( 3 )   1651 - 1656   2002.2

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    DOI： 10.1073/pnas.042416199

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MISC

Presentations

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Awards

  • 優秀発表賞

    2023.9   ⽇本解剖学会 第111回 関東⽀部学術集会  

    内田仁司

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  • 優秀演題

    2018.6   第40回 日本疼痛学会  

    内田 仁司

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  • 優秀演題

    2014.6   第36回 日本疼痛学会  

    内田 仁司

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  • Hot Topics

    2010.11   第40回 北米神経科学学会  

    内田 仁司

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  • 年会優秀発表賞

    2009.3   第82回 日本薬理学会年会  

    内田 仁司

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Research Projects

  • Frontier in research of meningeal macrophage opened up by tissue clearing

    Grant number：22K06443

    2022.4 - 2025.3

    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

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

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  • 慢性疼痛の発達に伴う時期特異的な神経回路の異常

    Grant number：20H03777

    2020.4 - 2025.3

    System name：科学研究費助成事業

    Research category：基盤研究(B)

    Awarding organization：日本学術振興会

    古賀 浩平, 内田 仁司

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    Grant amount：\17680000 （ Direct Cost: \13600000 、 Indirect Cost：\4080000 ）

    急性の痛みは生体防御に必要な感覚である一方、慢性疼痛は不快や嫌悪感から始まり、不安やうつなど負の情動を形成することが臨床で問題となっている。しかしながら、急性痛が慢性疼痛にいかに移行するかの過程や神経回路は未だ明らかになっていない。そこで、これまでに明らかにしてきた前帯状回のシナプス前終末の長期増強が慢性疼痛で惹起される不安様行動のシナプス可塑性である結果を基に、痛みに関連する神経回路の探索と投射選択的なシナプス可塑性の解析を行った。具体的には、視床は前帯状回に投射する痛み関連領域の一つであることが解剖学研究で明らかになっている。従って、マウスの視床の背内側核に順行性トレーサーを局所投与して脳組織を透明化した後、全脳イメージング手法であるCUBICで解析を行った。その結果、視床背内側核の神経細胞は、前帯状回に非常に強い投射があることを認めた。さらに、視床背内側核は前帯状回だけでなく、その他の痛み関連領域にも投射していることが明らかとなった。
    次に、光遺伝学と電気生理学的手法を組み合わせて前帯状回に投射する選択的なシナプス伝達を確立した。さらに、慢性疼痛の発達時期におけるシナプス可塑性を調べた。慢性疼痛モデルマウスの初期における視床ー前帯状回のシナプス伝達はシナプス前終末及び後膜に可塑的な変化を示した。さらに、慢性疼痛の３-４週間後の後期においても解析を行った結果、強いシナプス可塑性が形成が保存されていた。

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  • 慢性疼痛の発達に伴う時期特異的な神経回路の異常

    Grant number：23K20327

    2020.4 - 2025.3

    System name：科学研究費助成事業

    Research category：基盤研究(B)

    Awarding organization：日本学術振興会

    古賀 浩平, 内田 仁司

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    Grant amount：\17680000 （ Direct Cost: \13600000 、 Indirect Cost：\4080000 ）

    急性侵害刺激は、外的及び内的環境の変化を伝える危険信号として生体に重要な感覚であるが、侵害刺激が生体に持続的に加えられると、持続痛へと発達していく。痛みの持続化の特徴として、不快感など負の情動の形成がある。持続痛は、身体的要因と心因的要因の両要因が複雑かつ相互に影響を及ぼし合うと考えられているが、身体的要因と心因的要因を司るシナプス伝達機構や神経回路は不明である。
    本研究では、この急性から持続痛に発達する時の持続痛初期と後期に着目し、持続痛に発達する時の神経基盤を調べている。
    我々は、この持続痛を構成する身体的及び心因的要因の両要因に重要な前帯状回領域に着目し、持続痛モデルマウスの初期（１-２日）と後期（３-４週）におけるシナプス伝達の異常を解析した。電気生理学的手法と光遺伝学的手法を組み合わせて、前帯状回に投射する選択的なシナプス伝達が可塑的変化を示すか調べた。炎症性モデルマウスを作製し持続痛の初期と後期のそれぞれの時期で、前帯状回を含む脳スライス標本を作製した。前帯状回は、我々がCUBIC法でこれまでに明らかにしている視床ー前帯状回の投射以外にも痛みに関連する複数の脳領域から投射を受けてシナプスを形成している。従って、視床ー前帯状回とその他の領域ー前帯状回シナプスが持続痛もモデルの初期と後期で可塑的な変化を示すか比較検討した。次に、持続痛の初期に前帯状回で増加するターゲット因子の同定を行った。さらに、この標的分子マーカーの下流である受容体を前帯状回で阻害した時に炎症性マウスによる感覚過敏や嫌悪行動が緩和できるかについて行動薬理学的手法を用いて経時的および経日的に調べた。本年度は、炎症性モデルで発現が増加する分子マーカーの上流を電気生理学的および分子生物学的に調べた。

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  • Elucidation of neuroepigenetic mechanism underlying itch hypersensitivity in atopic dermatitis

    Grant number：19K07818

    2019.4 - 2022.3

    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

    Uchida Hitoshi

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

    The present study was aimed to identify the brain neuronal cells that mediate itch hypersensitivity in atopic dermatitis. To this end, the principal investigator developed a new tissue clearing method that can preserve the fluorescence signal. Also, we repeatedly conducted tissue clearing and 3D imaging analysis to comprehensively identify the brain neuronal cells that respond to itch or pain stimuli. In addition, the present study found that chronic itch was accompanied by activation of CNS-resident immune cells, microglia, in spinal cord and brain, by using tissue clearing and 3D imaging analysis.

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  • 神経障害性疼痛におけるRNA編集の役割解明

    2017.4 - 2019.3

    System name：科学研究費補助金 (若手研究(B))

    Awarding organization：日本学術振興会

    内田 仁司

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    Authorship：Principal investigator  Grant type：Competitive

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  • 神経障害性疼痛におけるエピジェネティックサイレンシングの統合的理解

    2014.4 - 2016.3

    System name：科学研究費補助金 (若手研究(B))

    Awarding organization：日本学術振興会

    内田 仁司

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    Authorship：Principal investigator  Grant type：Competitive

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  • LPAプライミングとiPS細胞を用いた慢性疼痛病態神経回路要素の再構成と創薬

    2014.4 - 2015.3

    System name：科学研究費補助金 (基盤研究(A))

    Awarding organization：日本学術振興会

    植田 弘師

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    Grant type：Competitive

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  • 難治性神経因性疼痛を担うエピジェネティクス異常とその調節機構の解明

    2011.4 - 2014.3

    System name：科学研究費補助金（特別研究員奨励費）

    Awarding organization：日本学術振興会

    内田 仁司

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    Authorship：Principal investigator  Grant type：Competitive

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  • 神経障害性疼痛における転写因子RESTの翻訳後修飾とその機能の解明

    2011.4 - 2012.3

    System name：平成23年度学内研究助成D1

    Awarding organization：関西医科大学

    内田 仁司

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    Authorship：Principal investigator  Grant type：Competitive

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  • 慢性疼痛を制御するエピジェネティクス：転写因子NRSF/RESTの機能解明

    2011.2 - 2012.1

    System name：平成22年度 研究奨励金

    Awarding organization：財団法人 東京生化学研究会

    内田 仁司

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    Authorship：Principal investigator  Grant type：Competitive

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  • 脂質シグナリングによる痛みの記憶化:エピジェネティクス制御機構の解明

    2010.4 - 2011.3

    System name：平成22年度 大学高度化推進経費 若手研究者への研究支援事業

    Awarding organization：長崎大学

    内田 仁司

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    Authorship：Principal investigator  Grant type：Competitive

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  • 脂質シグナリングによる痛みの記憶化:エピジェネティクス制御機構の解明

    2010.4 - 2011.3

    System name：科学研究費補助金 (基盤研究(C))

    Awarding organization：日本学術振興会

    内田 仁司

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    Authorship：Principal investigator  Grant type：Competitive

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  • ストレス性精神疾患の可視化とナノメディシン

    2009.4 - 2010.3

    System name：科学研究費補助金 (特定領域研究)

    Awarding organization：日本学術振興会

    植田 弘師

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    Grant type：Competitive

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  • 脱髄性神経損傷に起因する難治性神経因性疼痛の治療標的分子の同定

    2009.4 - 2010.3

    System name：科学研究費補助金 (基盤研究(S))

    Awarding organization：日本学術振興会

    植田 弘師

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    Grant type：Competitive

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