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Faculty of Medicine College Hospital Anesthesiology |
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Assistant Professor |
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Related SDGs |
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KOROKI Satoshi
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Papers 【 display / non-display 】
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丸田 豊明, 興梠 聡志
Molecular pain 22 17448069251414260 2026.1
Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications
Calcineurin inhibitors, including tacrolimus (FK506), are used as immunosuppressive agents and can cause unexplained calcineurin inhibitor-induced pain syndrome (CIPS). We investigated how FK506 affects the expression of NaV1.7, a voltage-gated Na+ channel implicated in pain perception that is upregulated in dorsal root ganglion (DRG) neurons in several pain disorders. We generated a model of FK506-induced pain by administering FK506 to NaV1.7-ChR2 mice, which exhibit light-responsive pain. To evaluate nociceptive responses, paw withdrawal threshold (PWT) was measured using the von Frey test. The optogenetic place aversion (OPA) and light irradiation paw withdrawal tests were also performed. On the 11th day of initial injection, DRGs were dissected from mice under anesthesia and analyzed for NaV1.7 expression using quantitative reverse transcription PCR (RT-qPCR). PWT was also measured for mice that received the selective NaV1.7 inhibitor or vehicle. PWT was lower in FK506-treated mice than in those administered the vehicle on the 8th and 12th days after initial injection (P < 0.05). Mechanical hypersensitivity was reversible and peaked at around 10 days after FK506 administration. OPA and light irradiation paw withdrawal test results corroborated the hypersensitivity to light-responsivity. NaV1.7 mRNA levels in DRG were higher in FK506-treated mice than in those administered the vehicle on the 11th day (P < 0.05). A selective NaV1.7 inhibitor reversed FK506-induced pain. Increased NaV1.7 expression in DRG neurons may be responsible for FK506-induced peripheral neuropathy. Our findings suggest that endogenous calcineurin regulates NaV1.7 expression. Thus, selective NaV1.7 inhibition could be a potential therapeutic strategy for CIPS.
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Maruta T., Shiraishi S., Kouroki S., Kurogi M., Hirata N.
Molecular Pain 22 17448069251414260 2026.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Molecular Pain
Calcineurin inhibitors, including tacrolimus (FK506), are used as immunosuppressive agents and can cause unexplained calcineurin inhibitor-induced pain syndrome (CIPS). We investigated how FK506 affects the expression of Na<inf>V</inf>1.7, a voltage-gated Na<sup>+</sup> channel implicated in pain perception that is upregulated in dorsal root ganglion (DRG) neurons in several pain disorders. We generated a model of FK506-induced pain by administering FK506 to Na<inf>V</inf>1.7–ChR2 mice, which exhibit light-responsive pain. To evaluate nociceptive responses, paw withdrawal threshold (PWT) was measured using the von Frey test. The optogenetic place aversion (OPA) and light irradiation paw withdrawal tests were also performed. On the 11th day of initial injection, DRGs were dissected from mice under anesthesia and analyzed for Na<inf>V</inf>1.7 expression using quantitative reverse transcription PCR (RT-qPCR). PWT was also measured for mice that received the selective Na<inf>V</inf>1.7 inhibitor or vehicle. PWT was lower in FK506-treated mice than in those administered the vehicle on the 8th and 12th days after initial FK506 injection (p < 0.05). Mechanical hypersensitivity was reversible and peaked at around 10 days after FK506 administration. OPA and light irradiation paw withdrawal test results corroborated the hypersensitivity to light-responsivity. Na<inf>V</inf>1.7 mRNA levels in DRG were higher in FK506-treated mice than in those administered the vehicle on the 11th day (p < 0.05). A selective Na<inf>V</inf>1.7 inhibitor reversed FK506-induced pain. Increased Na<inf>V</inf>1.7 expression in DRG neurons may be responsible for FK506-induced peripheral neuropathy. Our findings suggest that endogenous calcineurin regulates Na<inf>V</inf>1.7 expression. Thus, selective Na<inf>V</inf>1.7 inhibition could be a potential therapeutic strategy for CIPS.
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Kouroki S., Maruta T., Hidaka K., Koshida T., Kurogi M., Kage Y., Miura A., Nakagawa H., Yanagita T., Takeya R., Tsuneyoshi I.
Plos One 20 ( 5 May ) e0323628 2025.5
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：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 2024.10
Language：English Publishing type：Research paper (scientific journal) Publisher：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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症例報告 胸腺腫による心圧排所見を伴う発作性心房細動に対してランジオロールが奏効した1症例 Reviewed
興梠 聡志, 矢野 武志, 村社 瑞穂, 長嶺 佳弘, 古澤 高廣, 長濵 真澄, 與那覇 哲, 谷口 正彦, 恒吉 勇男
麻酔 72 ( 3 ) 285 - 290 2023.3
Presentations 【 display / non-display 】
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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 2026.3.7
Event date： 2026.3.5 - 2026.3.7
Language：Japanese Presentation type：Poster presentation
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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 2025.7.11
Event date： 2025.7.10 - 2025.7.12
Language：Japanese Presentation type：Oral presentation (general)
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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 2025.6.14
Event date： 2025.6.14
Language：Japanese Presentation type：Oral presentation (general)
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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
第52回日本集中治療医学会学術集会
Event date： 2025.3.14 - 2025.3.16
Language：Japanese Presentation type：Poster presentation
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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 2024.11.17
Event date： 2024.11.16 - 2024.11.17
Language：Japanese Presentation type：Oral presentation (general)