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医学部 附属病院 集中治療部 |
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助教 |
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論文 【 表示 ／ 非表示 】
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Satoshi Kouroki, Toyoaki Maruta, Kotaro Hidaka, Tomohiro Koshida, Mio Kurogi, Yohko Kage, Syako Miura, Hikarru Nakagawa, Toshihiko Yanagita, Ryu Takeya, Isao Tsuneyoshi
Plos One 20 ( 5 ) 2025年5月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Plos One
Neuropathic pain has a significant social impact, with high morbidity and reduced productivity, the underlying mechanisms of neuropathic pain remain poorly understood, and effective therapeutic strategies remain elusive. The development of animal models of neuropathic pain that stimulate only the nociceptors and not the other sensory receptors or motor nerves is desirable for elucidating the complex pathogenesis of neuropathic pain. We have previously reported the generation of Na<inf>V</inf>1.7−channelrhodopsin-2 (ChR2), Na<inf>V</inf>1.8−ChR2, and Na<inf>V</inf>1.9−ChR2 mice. Optogenetics was employed in these light-responsive pain mice for generating nociceptive pain by specifically exciting the spinal dorsal root ganglion neurons, in which the respective Na<sup>+</sup> channels are expressed through exposure to blue light. This study aimed to compare the neuropathic pain produced by the prolonged exposure of light-responsive pain mice to blue light. A reversible neuropathic pain state was established persisting for a minimum of 24 hours when each light-responsive pain mouse was irradiated with light of an intensity that consistently elicited pain. Furthermore, the mice also showed pain sensitivity to light irradiation and mechanical stimulation. The expression of c-Fos, a marker for neuronal activity following noxious stimulation, was increased in the dorsal horn of the spinal cord on the light irradiated side. DS-1971a, a selective Na<inf>V</inf>1.7 inhibitor, was effective in attenuating neuropathic pain in all light-responsive pain mice. In conclusion, optogenetics helps elucidate the specific functions of sodium channel subtypes in pain signaling, thereby advancing our understanding and paving the way for the development of further effective treatments for pain disorders in the future.
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Maruta T., Kouroki S., Kurogi M., Hidaka K., Koshida T., Miura A., Nakagawa H., Yanagita T., Takeya R., Tsuneyoshi I.
Journal of Neuroscience Research 102 ( 10 ) e25386 2024年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Neuroscience Research
Voltage-gated sodium channels, including NaV1.7, NaV1.8, and NaV1.9, play important roles in pain transmission and chronic pain development. However, the specific mechanisms of their action remain unclear, highlighting the need for in vivo stimulation studies of these channels. Optogenetics, a novel technique for targeting the activation or inhibition of specific neural circuits using light, offers a promising solution. In our previous study, we used optogenetics to selectively excite NaV1.7-expressing neurons in the dorsal root ganglion of mice to induce nocifensive behavior. Here, we further characterize the impact of nocifensive behavior by activation of NaV1.7, NaV1.8, or NaV1.9-expressing neurons. Using CRISPR/Cas9-mediated homologous recombination, NaV1.7–iCre, NaV1.8–iCre, or NaV1.9–iCre mice expressing iCre recombinase under the control of the endogenous NaV1.7, NaV1.8, or NaV1.9 gene promoter were produced. These mice were then bred with channelrhodopsin-2 (ChR2) Cre–reporter Ai32 mice to obtain NaV1.7–ChR2, NaV1.8–ChR2, or NaV1.9–ChR2 mice. Blue light exposure triggered paw withdrawal in all mice, with the strongest response in NaV1.8–ChR2 mice. These light sensitivity differences observed across NaV1.x–ChR2 mice may be dependent on ChR2 expression or reflect the inherent disparities in their pain transmission roles. In conclusion, we have generated noninvasive pain models, with optically activated peripheral nociceptors. We believe that studies using optogenetics will further elucidate the role of sodium channel subtypes in pain transmission.
DOI： 10.1002/jnr.25386
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透析用バスキュラーアクセスカテーテルが上行腰静脈に迷入し腸腰筋血腫を呈した1症例 査読あり
古澤 高廣, 矢野 武志, 菓子野 里奈, 吉海 瑞穂, 越田 智広, 與那覇 哲, 谷口 正彦, 恒吉 勇男
日本集中治療医学会雑誌 30 ( 1 ) 23 - 24 2023年1月
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Koshida T., Maruta T., Tanaka N., Hidaka K., Kurogi M., Nemoto T., Yanagita T., Takeya R., Tsuneyoshi I.
Acta Medica Okayama 77 ( 4 ) 359 - 364 2023年
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Acta Medica Okayama
Pulsed radiofrequency (PRF) is a safe method of treating neuropathic pain by generating intermittent electric fields at the needle tip. Resiniferatoxin (RTX) is an ultrapotent agonist of transient receptor potential vanilloid subtype-1 (TRPV1) receptors. We investigated the mechanism of PRF using a rat model of RTX-induced neuropathic pain. After administering RTX intraperitoneally, PRF was applied to the right sciatic nerve. We observed the changes in TRPV1, calcitonin gene-related peptide (CGRP), and brain-derived neurotrophic factor (BDNF) in the dorsal root ganglia by western blotting. Expressions of TRPV1 and CGRP were significantly lower in the contralateral (RTX-treated, PRF-untreated) tissue than in control rats (p<0.0001 and p<0.0001, respectively) and the ipsilateral tissues (p<0.0001 and p<0.0001, respectively). BDNF levels were significantly higher in the contralateral tissues than in the control rats (p<0.0001) and the ipsilateral tissues (p<0.0001). These results suggest that, while TRPV1 and CGRP are decreased by RTX-induced neuronal damage, increased BDNF levels result in pain development. PRF may promote recovery from neuronal damage with concomitant restoration of TRPV1 and CGRP, and exert its analgesic effect by reversing BDNF increase. Further research is required to understand the role of TRPV1 and CGRP restoration in improving mechanical allodynia.
DOI： 10.18926/AMO/65741
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Maruta T., Hidaka K., Kouroki S., Koshida T., Kurogi M., Kage Y., Mizuno S., Shirasaka T., Yanagita T., Takahashi S., Takeya R., Tsuneyoshi I.
PLoS ONE 17 ( 10 October ) e0275751 2022年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：PLoS ONE
In small and large spinal dorsal root ganglion neurons, subtypes of voltage-gated sodium channels, such as NaV1.7, NaV1.8, and NaV1.9 are expressed with characteristically localized and may play different roles in pain transmission and intractable pain development. Selective stimulation of each specific subtype in vivo may elucidate its role of each subtype in pain. So far, this has been difficult with current technology. However, Optogenetics, a recently developed technique, has enabled selective activation or inhibition of specific neural circulation in vivo. Moreover, optogenetics had even been used to selectively excite NaV1.8-expressing dorsal root ganglion neurons to induce nocifensive behavior. In recent years, genetic modification technologies such as CRISPR/Cas9 have advanced, and various knock-in mice can be easily generated using such technology. We aimed to investigate the effects of selective optogenetic activation of NaV1.7-expressing afferents on mouse behavior. We used CRISPR/Cas9-mediated homologous recombination to generate bicistronic NaV1.7–iCre knock-in mice, which express iCre recombinase under the endogenous NaV1.7 gene promoter without disrupting NaV1.7. The Cre-driver mice were crossed with channelrhodopsin-2 (ChR2) Cre-reporter Ai32 mice to obtain NaV1.7iCre/+;Ai32/+, NaV1.7iCre/iCre;Ai32/+, NaV1.7iCre/+;Ai32/Ai32, and NaV1.7iCre/iCre;Ai32/Ai32 mice. Compared with wild–type mice behavior, no differences were observed in the behaviors associated with mechanical and thermal stimuli exhibited by mice of the aforementioned genotypes, indicating that the endogenous NaV1.7 gene was not affected by the targeted insertion of iCre. Blue light irradiation to the hind paw induced paw withdrawal by mice of all genotypes in a light power-dependent manner. The threshold and incidence of paw withdrawal and aversive behavior in a blue-lit room were dependent on ChR2 expression level; the strongest response was observed in NaV1.7iCre/iCre;Ai32/Ai32 mice. Thus, we developed a non-invasive pain model in which peripheral nociceptors were optically activated in free-moving transgenic NaV1.7–ChR2 mice.
講演・口頭発表等 【 表示 ／ 非表示 】
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クラゾセンタン投与後早期に吸気性喘鳴を聴取し，喉頭浮腫が疑われた１例．
内村修二，谷口正彦，興梠聡志，越田智広，與那覇 哲，山下幸貴，恒吉勇男
第53回日本集中治療医学会学術集会 2026年3月7日
開催年月日： 2026年3月5日 - 2026年3月7日
記述言語：日本語 会議種別：ポスター発表
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レシニフェラトキシン誘発性疼痛ラットでのPRFによる神経再生効果の検討（優秀演題）．
越田智広，興梠聡志，丸田豊明，日髙康太郎，前田充範，山賀昌治，恒吉勇男
日本ペインクリニック学会第59回学術集会 2025年7月11日
開催年月日： 2025年7月10日 - 2025年7月12日
記述言語：日本語 会議種別：口頭発表（一般）
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腹臥位療法により肺動脈圧の著名な低下を認めたインフルエンザ肺炎合併急性心筋梗塞後心不全の一例．
與那覇 哲，米良 舞，興梠聡志，内村修二，越田智広，山下幸貴，矢野武志，谷口正彦，恒吉勇男
日本集中治療医学会第９回九州支部学術集会 2025年6月14日
開催年月日： 2025年6月14日
記述言語：日本語 会議種別：口頭発表（一般）
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選択的血漿交換療法が奏効した抗体陰性視神経脊髄炎の１症例．
越田智広，山下幸貴，與那覇 哲，内村修二，興梠聡志，米良 舞，谷口正彦，恒吉勇男
第52回日本集中治療医学会学術集会
開催年月日： 2025年3月14日 - 2025年3月16日
記述言語：日本語 会議種別：ポスター発表
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光応答性疼痛マウスに持続的な光照射をすることで作製した神経障害性疼痛モデルの検討．
興梠聡志，丸田豊明，日髙康太郎，越田智広，恒吉勇男
第46回日本疼痛学会 2024年11月17日
開催年月日： 2024年11月16日 - 2024年11月17日
記述言語：日本語 会議種別：口頭発表（一般）