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医学部 附属病院 麻酔科 |
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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
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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Hidaka K, Maruta T, Koshida T, Kurogi M, Kage Y, Kouroki S, Shirasaka T, Takeya R, Tsuneyoshi I
Molecular pain 18 17448069221089784 2022年1月
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：Molecular Pain
Pulsed radiofrequency (PRF) therapy is one of the most common treatment options for neuropathic pain, albeit the underlying mechanism has not been hitherto elucidated. In this study, we investigated the efficacy and mechanism of PRF therapy on resiniferatoxin (RTX)-induced mechanical allodynia, which has been used as a model of postherpetic neuralgia (PHN). Adult male rats were intraperitoneally injected with a vehicle or RTX. Furthermore, PRF current was applied on a unilateral sciatic nerve in all RTX-treated rats. On both ipsilateral and contralateral sides, the paw mechanical withdrawal thresholds were examined and L4-6 dorsal root ganglia (DRG) were harvested. In the DRG of rats with RTX-induced mechanical allodynia, NaV1.7, a voltage-gated Na+ channel, was upregulated following the enhancement of extracellular signal-regulated kinase phosphorylation. Early PRF therapy, which was applied 1 week after RTX exposure, suppressed this NaV1.7 upregulation and showed an anti-allodynic effect; however, late PRF therapy, which was applied after 5 weeks of RTX exposure, failed to inhibit allodynia. Interestingly, late PRF therapy became effective after daily tramadol administration for 7 days, starting from 2 weeks after RTX exposure. Both early PRF therapy and late PRF therapy combined with early tramadol treatment suppressed NaV1.7 upregulation in the DRG of rats with RTX-induced mechanical allodynia. Therefore, NaV1.7 upregulation in DRG is related to the development of RTX-induced neuropathic pain; moreover, PRF therapy may be effective in the clinical management of patients with PHN via NaV1.7 upregulation inhibition.
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左上肢運動麻痺，著明な浮腫を合併した帯状疱疹関連痛に対し，ステロイドパルス療法が有効であった１症例． 査読あり
内村修二，山賀昌治，川﨑祐子，日髙康太郎，渡部由美，恒吉勇男
日本ペインクリニック学会誌 29 ( 1 ) 9 - 11 2022年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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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 ) e0275751 2022年
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.
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難治性がん性疼痛に対する治療法の選択が難航した症例． 査読あり
門田瑤子，内村修二，日髙康太郎，川﨑祐子，渡部由美，山賀昌治，恒吉勇男
日本ペインクリニック学会誌 27 ( 3 ) 1 - 17 2020年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
講演・口頭発表等 【 表示 ／ 非表示 】
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難治性後頭部痛に対して，大後頭神経へのパルス高周波法が有効であった一症例．
吉海瑞穂，日髙康太郎，渡部由美，山賀昌治，恒吉勇男
日本ペインクリニック学会第２回九州支部学術集会
開催年月日： 2022年2月28日 - 2022年3月13日
記述言語：日本語 会議種別：口頭発表（一般）
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帯状疱疹後神経痛モデルラットにおける高周波パルス療法の作用機序の検討．
日髙康太郎，丸田豊明，越田智広，興梠聡志，白阪哲朗，恒吉勇男
第43回日本疼痛学会
開催年月日： 2021年12月10日 - 2021年12月11日
記述言語：日本語 会議種別：口頭発表（一般）
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声門上デバイス（i-gel）下に摘出した小児気管支内異物の１例．
押川 隆，永田悠紀子，日髙康太郎，白阪哲朗，恒吉勇男
九州麻酔科学会第59回大会
開催年月日： 2021年9月4日 - 2021年10月4日
記述言語：日本語 会議種別：口頭発表（一般）
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術後の疼痛コントロールに難渋したブプレノルフィン貼付剤使用患者の一例．
門田瑶子，日髙康太郎，内村修二，渡部由美，山賀昌治，恒吉勇男
日本ペインクリニック学会第55回大会
開催年月日： 2021年7月22日 - 2021年7月24日
記述言語：日本語 会議種別：口頭発表（一般）
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レシニフェラトキシン誘発性疼痛ラットでのトラマドール治療後の高周波パルス療法の有効性と作用機序の検討（優秀演題）．
日髙康太郎，丸田豊明，門田瑶子，興梠聡志，越田智広，渡部由美，山賀昌治，恒吉勇男
日本ペインクリニック学会第55回大会
開催年月日： 2021年7月22日 - 2021年7月24日
記述言語：日本語 会議種別：口頭発表（一般）
科研費（文科省・学振・厚労省）獲得実績 【 表示 ／ 非表示 】
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NaV1.7を標的とする疼痛治療薬の光遺伝学的探索：トラマドールとミロガバリン
研究課題/領域番号：23K15603 2023年04月 - 2026年03月
独立行政法人日本学術振興会 科学研究費基金 若手研究
担当区分：研究代表者