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NOMURA YukiUniversity Hospital / Anesthesiology and Pain ClinicAssociate Professor
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■ Paper- BACKGROUND: Spinal cord stimulation (SCS) is widely accepted as a useful treatment for patients with intractable chronic pain. However, its effectiveness varies between individuals. Therefore, a tool for evaluating its effectiveness in advance is eagerly awaited. We examined whether resting-state functional magnetic resonance imaging as a diagnostic and prognostic tool can predict responsiveness to SCS. METHODS: Twenty-nine patients with intractable chronic pain participated in this study. Participants were divided into responder and non-responder groups based on a pain relief rate after SCS trials. All participants underwent resting-state functional magnetic resonance imaging scans before the SCS trials. We searched for functional connectivity that differed significantly in strength between the two groups and was correlated with pain relief rate. We conducted receiver operating characteristic (ROC) analysis and a one-sample proportion test to determine the cut-off value and evaluate the predictive power of the functional connectivity-based prediction model. RESULTS: In total, 14 and 15 participants were assigned to the responder and non-responder groups, respectively. Functional connectivity between the middle anterior cingulate cortex and precuneus/posterior cingulate cortex showed significant between-group differences and a significant negative correlation with the pain relief rate. Moreover, this functional connectivity could accurately predict SCS responsiveness greater than chance (sensitivity: 71%; specificity: 87%; area under the curve: 0.814; P<0.001). CONCLUSIONS: For patients with intractable chronic pain, functional connectivity between the middle anterior cingulate cortex and precuneus/posterior cingulate cortex is a promising candidate biomarker to estimate responsiveness to spinal cord stimulation before treatment.Feb. 2025, British journal of anaesthesia, 134(2) (2), 492 - 500, English, International magazineScientific journal
- OBJECTIVE: Patients with chronic pain often have sleep disturbances, and many patients receive sleep medications in addition to analgesics. Although there have been scattered reports of negative pain-sleep interactions, only a few reports have investigated the efficacy of sleep medication interventions in patients with chronic pain for improving sleep disturbances and reducing pain. We retrospectively examined whether lemborexant, an orexin receptor antagonist, is effective in improving sleep disturbances and reducing pain in patients with chronic pain. This study was approved by the Ethics Committee of our hospital. METHODS: The subjects were 26 patients with chronic pain undergoing treatment at our pain clinic between July 2021 and March 2022, who had been diagnosed with insomnia, with an Athens Insomnia Scale (AIS) score of ≥6 and had been started on lemborexant. The AIS score and pain score (Numeric Rating Scale [NRS]) before and after 2 and 4 weeks of starting lemborexant were investigated. RESULTS: Patients who were already taking other sleep medications, such as benzodiazepines were switched to 5 mg of lemborexant after all the other sleep medications were discontinued. Those who had not yet used sleeping pills were started on 5 mg of lemborexant. During the study course, the dose of lemborexant was adjusted at the discretion of the attending physician, based on improvement of insomnia symptoms and secondary symptoms, such as daytime sleepiness and lightheadedness. The study finally included 21 patients, excluding 5 who could not continue taking lemborexant due to side effects, such as lightheadedness. The AIS scores significantly improved, decreasing from baseline (mean ± standard deviation: 12.5 ± 4.9) to 2 weeks (7.8 ± 3.1) and 4 weeks (5.3 ± 2.9) after the start of lemborexant. No significant difference was observed in the degree of improvement in sleep disturbance between patients with or without previous sleep medications, and there was also no statistically significant improvement in the NRS score before (6.1 ± 2.7) and after 2 weeks (5.5 ± 2.3) and 4 weeks (5.9 ± 2.2) from treatment initiation.Feb. 2024, Pain medicine (Malden, Mass.), 25(2) (2), 139 - 143, English, International magazineScientific journal
- American Society for Clinical Investigation, Jul. 2021, Journal of Clinical Investigation, 131(13) (13)Scientific journal
- Sustained neuropathic pain from injury or inflammation remains a major burden for society. Rodent pain models have informed some cellular mechanisms increasing neuronal excitability within the spinal cord and primary somatosensory cortex (S1), but how activity patterns within these circuits change during pain remains unclear. We have applied multiphoton in vivo imaging and holographic stimulation to examine single S1 neuron activity patterns and connectivity during sustained pain. Following pain induction, there is an increase in synchronized neuronal activity and connectivity within S1, indicating the formation of pain circuits. Artificially increasing neuronal activity and synchrony using DREADDs reduced pain thresholds. The expression of N-type voltage-dependent Ca2+ channel subunits in S1 was increased after pain induction, and locally blocking these channels reduced both the synchrony and allodynia associated with inflammatory pain. Targeting these S1 pain circuits, via inhibiting N-type Ca2+ channels or other approaches, may provide ways to reduce inflammatory pain.American Association for the Advancement of Science (AAAS), Mar. 2021, Science Advances, 7(12) (12), eabd8261 - eabd8261Scientific journal
- Ovid Technologies (Wolters Kluwer Health), Feb. 2021, Pain, 162(2) (2), 446 - 458Scientific journal
- Springer Science and Business Media LLC, Dec. 2020, BMC Endocrine Disorders, 20(1) (1)
Abstract Background The risk of surgical site infection has been reported to be higher in patients with poorly controlled diabetes. Since chronic hyperglycemia impairs neutrophil functions, preoperative glycemic control may restore neutrophil function. However, long-term insulin therapy may lead to a delay in surgery, which may be a problem, especially in cancer surgery. It is therefore unfortunate that there have been few studies in which the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia was investigated. Therefore, we investigated the effects of preoperative long-term insulin therapy and short-term insulin therapy on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia.Methods Five-week-old male C57BL/6 J mice were divided into four groups (No insulin (Diabetes Mellitus: DM), Short-term insulin (DM), Long-term insulin (DM), and Non-diabetic groups). Diabetes was established by administrating repeated low-dose streptozotocin. The Short-term insulin (DM) group received insulin therapy for 6 h before the operation and the Long-term insulin (DM) group received insulin therapy for 5 days before the operation. The No insulin (DM) group and the Non-diabetic group did not receive insulin therapy. At 14 weeks of age, abdominal surgery with intestinal manipulation was performed in all four groups. We carried out a phagocytosis assay with fluorescent microspheres and a reactive oxygen species (ROS) production assay with DCFH-DA (2′,7′-dichlorodihydrofluorescein diacetate) before and 24 h after the operation using FACSVerse™ with BD FACSuite™ software.Results Blood glucose was lowered by insulin therapy in the Short-term insulin (DM) and Long-term insulin (DM) groups before the operation. Neutrophilic phagocytosis activities before and after the operation were significantly restored in the Long-term insulin (DM) group compared with those in the No insulin (DM) group (before:p = 0.0008, after:p = 0.0005). However, they were not significantly restored in the Short-term insulin (DM) group. Neutrophilic ROS production activities before and after the operation were not restored in either the Short-term insulin (DM) group or Long-term insulin (DM) group.Conclusions Preoperative and postoperative phagocytosis activities are restored by insulin therapy for 5 days before the operation but not by insulin therapy for 6 h before the operation.Scientific journal - We report a successful case of fluoroscopic percutaneous retrocrural coeliac plexus neurolysis (PRCPN) for pancreatic cancer pain refractory to endoscopic ultrasound-guided coeliac plexus neurolysis (EUS-CPN). A 55-year-old man with upper abdominal pain due to end-stage pancreatic cancer underwent EUS-CPN. Although CT revealed distribution of the contrast medium with neurolytic agent around the left and cephalic sides of the coeliac artery, the pain did not improve and became even more severe. PRCPN was performed, resulting in the drastic improvement of pain immediately. PRCPN should be considered when EUS-CPN is not effective.BMJ, Jun. 2020, BMJ Supportive & Palliative Care, bmjspcare - 2020Scientific journal
- BACKGROUND: There has been much discussion recently about the occurrence of neuropsychological complications during the perioperative period. Diabetes is known to be one of the metabolic risk factors. Although the number of patients with diabetes mellitus (DM) has been increasing, the pathophysiology of postoperative neuropsychological dysfunction in DM patients is still unclear. Recently, a deficiency of neurotransmitters, such as monoamines, was reported to be associated with mental disorders. Therefore, we investigated the effects of surgical stress on behavioral activity and hippocampal noradrenaline (NA) level in type 2 diabetes mellitus model (T2DM) mice. METHODS: Eighty-four 6-week-old male C57BL/6J mice were divided into four groups (non-diabetes, non-diabetes with surgery, T2DM, and T2DM with surgery groups). T2DM mice were established by feeding a high-fat diet (HFD) for 8 weeks. At 14 weeks of age, fifteen mice in each group underwent a series of behavioral tests including an open field (OF) test, a novel object recognition (NOR) test and a light-dark (LD) test. In the surgery groups, open abdominal surgery with manipulation of the intestine was performed 24 h before the behavioral tests as a surgical stress. Hippocampal noradrenaline (NA) concentration was examined in six mice in each group by high-performance liquid chromatography. The data were analyzed by the Mann-Whitney U test, and p values less than 0.05 were considered significant. RESULTS: The T2DM group showed significantly increased explorative activity in the NOR test (P = 0.0016) and significantly increased frequency of transition in the LD test (P = 0.043) compared with those in the non-diabetic group before surgery. In T2DM mice, surgical stress resulted in decreased total distance in the OF test, decreased explorative activity in the NOR test, and decreased frequency of transition in the LD test (OF: P = 0.015, NOR: P = 0.009, LD: P = 0.007) and decreased hippocampal NA (P = 0.015), but such differences were not observed in the non-diabetic mice. CONCLUSIONS: Mice with T2DM induced by feeding an HFD showed increased behavioral activities, and surgical stress in T2DM mice caused postoperative hypoactivity and reduction of the hippocampal NA level.Feb. 2020, BMC neuroscience, 21(1) (1), 8 - 8, English, International magazine[Refereed]Scientific journal
- Jun. 2016, JOURNAL OF ANESTHESIA, 30(3) (3), 489 - 492, English[Refereed]Scientific journal
- Springer Science and Business Media LLC, Aug. 2012, Journal of Anesthesia, 26(4) (4), 490 - 495, EnglishScientific journal
- Springer Science and Business Media LLC, Oct. 2010, Journal of Anesthesia, 24(5) (5), 669 - 674, EnglishScientific journal
- Non-structural protein 4A (NS4A) of Hepatitis C virus (HCV) functions as a cofactor for NS3 by forming a complex with it to augment its enzymic activities. NS4A also forms a complex with other HCV proteins, such as NS4B/NS5A, to facilitate the formation of the viral RNA replication complex on the endoplasmic reticulum (ER) membrane. In addition to its essential role in HCV replication, NS4A is thought to be involved in viral pathogenesis by affecting cellular functions. In this study, it was demonstrated that NS4A was localized not only on the ER, but also on mitochondria when expressed either alone or together with NS3 in the form of the NS3/4A polyprotein and in the context of HCV RNA replication in Huh7 cells harbouring an HCV RNA replicon. Moreover, NS4A expression altered the intracellular distribution of mitochondria significantly and caused mitochondrial damage, as evidenced by the collapsed mitochondrial transmembrane potential and release of cytochrome c into the cytoplasm, which led ultimately to induction of apoptosis through activation of caspase-3, but not caspase-8. Consistently, Huh7 cells expressing NS3/4A and those harbouring an HCV RNA replicon were shown to be more prone to undergoing actinomycin D-induced, mitochondria-mediated apoptosis, compared with the control Huh7 cells. Taken together, these results suggest the possibility that HCV exerts cytopathic effect (CPE) on the infected cells under certain conditions and that NS4A is responsible, at least in part, for the conditional CPE in HCV-infected cells.Jul. 2006, The Journal of general virology, 87(Pt 7) (Pt 7), 1935 - 1945, English, International magazineScientific journal
- The N-terminal 198 residues of NS3 (NS3-N) of Hepatitis C virus (HCV) subtype 1b obtained from 29 patients, as well as full-length NS3 (NS3-Full), were analysed for their subcellular localization, interaction with the tumour suppressor p53 and serine protease activity in the presence and absence of the viral cofactor NS4A. Based on the subcellular-localization patterns in the absence of NS4A, NS3-N sequences were classified into three groups, with each group exhibiting either dot-like, diffuse or a mixed type of localization. Chimeric NS3-Full sequences, each consisting of an individual NS3-N and a shared C-terminal sequence, showed the same localization patterns as those of the respective NS3-N. Site-directed mutagenesis experiments revealed that a single or a few amino acid substitutions at a particular position(s) of NS3-N altered the localization pattern. Interestingly, NS3 of the dot-like type, either NS3-N or NS3-Full, interacted with p53 more strongly than that of the diffuse type, in both the presence and the absence of NS4A. Moreover, NS3-N of the dot-like type suppressed trans-activating activity of p53 more strongly than that of the diffuse type. Serine protease activity did not differ significantly between the two types of NS3. In HCV RNA replicon-harbouring cells, physical interaction between NS3 and p53 was observed consistently and p53-mediated transcriptional activation was suppressed significantly compared with HCV RNA-negative control cells. Our results collectively suggest the possibility that NS3 plays an important role in the hepatocarcinogenesis of HCV by interacting differentially with p53 in an NS3 sequence-dependent manner.Jun. 2006, The Journal of general virology, 87(Pt 6) (Pt 6), 1703 - 1713, English, International magazineScientific journal
- The NS3 protein of hepatitis C virus (HCV) has a serine protease activity in its N-terminal region, which plays a crucial role in virus replication. This region has also been reported to interact not only with its viral cofactor NS4A, but also with a number of host-cell proteins, which suggests a multifunctional feature of NS3. By means of yeast two-hybrid screening using an N-terminal region of NS3 as bait, a human cDNA encoding a region of ELKS-delta, a member of a novel family of proteins involved in intracellular transport and secretory pathways, was molecularly cloned. Using co-immunoprecipitation, GST pull-down and confocal and immunoelectron microscopic analyses, it was shown that full-length NS3 interacted physically with full-length ELKS-delta and its splice variant, ELKS-alpha, both in the absence and presence of NS4A, in cultured human cells, including Huh-7 cells harbouring an HCV subgenomic RNA replicon. The degree of binding to ELKS-delta varied with different sequences of the N-terminal 180 residues of NS3. Interestingly, NS3, either full-length or N-terminal fragments, enhanced secretion of secreted alkaline phosphatase (SEAP) from the cells, and the increase in SEAP secretion correlated well with the degree of binding between NS3 and ELKS-delta. Taken together, these results suggest the possibility that NS3 plays a role in modulating host-cell functions such as intracellular transport and secretion through its binding to ELKS-delta and ELKS-alpha, which may facilitate the virus life cycle and/or mediate the pathogenesis of HCV.Aug. 2005, The Journal of general virology, 86(Pt 8) (Pt 8), 2197 - 2208, English, International magazineScientific journal
- Suppression of hepatitis C virus replicon by RNA interference directed against the NS3 and NS5B regions of the viral genome.RNA interference (RNAi) is a phenomenon in which small interfering RNA (siRNA), an RNA duplex 21 to 23 nucleotides (nt) long, or short hairpin RNA (shRNA) resembling siRNA, mediates degradation of the target RNA molecule in a sequence-specific manner. RNAi is now expected to be a useful therapeutic strategy for hepatitis C virus (HCV) infection. In the present study we compared the efficacy of a number of shRNAs directed against different target regions of the HCV genome, such as 5'-untranslated region (5'UTR) (nt 286 to 304), Core (nt 371 to 389), NS3-1 (nt 2052 to 2060), NS3-2 (nt 2104 to 2122), and NS5B (nt 7326 to 7344), all of which except for NS5B are conserved among most, if not all, HCV subtype 1b (HCV-1b) isolates in Japan. We utilized two methods to express shRNAs, one utilizing an expression plasmid (pAVU6+27) and the other utilizing a recombinant lentivirus harboring the pAVU6+27-derived expression cassette. Although 5'UTR has been considered to be the most suitable region for therapeutic siRNA and/or shRNA because of its extremely high degree of sequence conservation, we observed only a faint suppression of an HCV subgenomic replicon by shRNA against 5'UTR. In both plasmid-and lentivirus-mediated expression systems, shRNAs against NS3-1 and NS5B suppressed most efficiently the replication of the HCV replicon without suppressing host cellular gene expression. Synthetic siRNA against NS3-1 also inhibited replication of the HCV replicon in a dose-dependent manner. Taken together, the present results imply the possibility that the recombinant lentivirus expressing shRNA against NS3-1 would be a useful tool to inhibit HCV-1b infection.2004, Microbiology and immunology, 48(8) (8), 591 - 8, English, International magazineScientific journal
- Physical interaction between hepatitis C virus NS4B protein and CREB-RP/ATF6beta.By using a yeast two-hybrid assay, cyclic AMP-response-element-binding protein-related protein (CREB-RP), also called activating transcription factor 6beta (ATF6beta), was identified as a cellular protein that interacts with the NS4B protein of hepatitis C virus. An N-terminal half of NS4B and a central portion of CREB-RP/ATF6beta containing the basic leucine zipper (bZIP) domain were involved in the interaction. The interaction between NS4B and CREB-RP/ATF6beta was demonstrated also in mammalian cells by co-immunoprecipitation and confocal microscopic analyses using specific antibodies. The bZIP domain of ATF6alpha, which shares high sequence similarity with CREB-RP/ATF6beta, was also shown to interact with NS4B in yeast although the interaction was weaker than that between NS4B and CREB-RP/ATF6beta. CREB-RP/ATF6beta and ATF6alpha are known as endoplasmic reticulum (ER) stress-induced transcription factors. Collectively, our results imply the possibility that NS4B modulates certain cellular responses upon ER stress through the physical interaction with CREB-RP/ATF6beta and ATF6alpha.Dec. 2002, Biochemical and biophysical research communications, 299(3) (3), 366 - 72, English, International magazineScientific journal
- 2025, 日本ペインクリニック学会誌(Web), 32(2) (2)多剤服用となっていた化学療法誘発性末梢神経障害性疼痛患者に対し入院による薬剤調整
- 2024, 日本麻酔科学会学術集会(Web), 71stAssessing the impact of general anesthetics on neuronal activity in the cerebral cortex through in vivo calcium imaging
- 2024, 日本麻酔科学会学術集会(Web), 71stEffects of general anesthetics on mitochondrial metabolism and reactive oxygen species production in cultured neutrophil cells
- 2024, 日本麻酔科学会学術集会(Web), 71stRole of brain microglia in gender difference of neuropathic pain
- 2024, 日本麻酔科学会学術集会(Web), 71stAdministration of beta2-adrenergic receptor agonists reduces mechanical allodynia in a mouse model of neuropathic pain
- 2024, 日本ペインクリニック学会誌(Web), 31(program) (program)迷走神経及び舌咽神経領域の帯状疱疹関連痛の1例
- 2024, 日本ペインクリニック学会誌(Web), 31(program) (program)当院における抜歯後感覚障害に対する星状神経節ブロックの効果の検討
- (一社)日本ペインクリニック学会, Jun. 2023, 日本ペインクリニック学会誌, 30(プログラム号) (プログラム号), 418 - 418, Japanese当院における脊髄障害性疼痛に対する脊髄刺激療法の効果の検討
- (一社)日本ペインクリニック学会, Mar. 2023, 日本ペインクリニック学会誌, 30(3) (3), 61 - 62, Japanese
- 2023, Pain Research (Web), 38(Supplement) (Supplement)Resting-brain functional connectivity in patients with chronic neuropathic pain who responded to short-term spinal cord stimulation therapy
- 克誠堂出版(株), Nov. 2022, 麻酔, 71(増刊) (増刊), S163 - S170, Japanese
- (一社)日本ペインクリニック学会, Aug. 2022, 日本ペインクリニック学会誌, 29(8) (8), 177 - 181, Japanese
- (一社)日本ペインクリニック学会, Jun. 2022, 日本ペインクリニック学会誌, 29(プログラム号) (プログラム号), 104 - 104, Japanese慢性痛患者におけるレンボレキサントによる睡眠改善と痛みの関連に関する検討
- (一社)日本ペインクリニック学会, Apr. 2022, 日本ペインクリニック学会誌, 29(4) (4), 65 - 65, Japanese
- (一社)日本ペインクリニック学会, Jun. 2021, 日本ペインクリニック学会誌, 28(プログラム号) (プログラム号), O6 - 6, Japanese帯状疱疹関連痛に対するフェンタニルを用いた疼痛機序判別試験の有用性について
- (一社)日本ペインクリニック学会, Jun. 2021, 日本ペインクリニック学会誌, 28(プログラム号) (プログラム号), O19 - 6, Japaneseslipping rib syndromeに対して神経ブロックが著効した一例
- Oct. 2018, 日本小児麻酔学会誌, 24脊髄性筋萎縮症に対するヌシネルセン髄腔内投与における治療体制の構築
- Jan. 2016, Anet, 3 - 6, Japanese遺伝子多型とは何か?(遺伝子多型の基礎を知る)Introduction scientific journal
- Jul. 2015, 臨床麻酔, 39(7) (7), Japanese麻酔科領域に関与する遺伝子多型Introduction scientific journal
- 第111回 近畿生理学談話会, Nov. 2018, Japanese, 和歌山, Domestic conference大脳皮質感覚野の生体イメージングによる疼痛発症機構解明へのアプローチOral presentation
- Neuroscience 2018, Nov. 2018, English, San Diego, CA, International conferenceIn vivo tracing of single neuron activity with Ca2+ imaging of primary somatosensory cortex in mouse models of postoperative pain and inflammatory painPoster presentation
- 日本小児麻酔学会第24回大会, Oct. 2018, Japanese, 神戸, Domestic conference先天性サイトメガロウイルス感染に対して胎児治療を施した2症例の麻酔経験Poster presentation
- Cold Spring Harbor Asia Confference, Sep. 2018, English, 淡路, International conferenceIn vivo tracing of single neuron activity with Ca2+ imaging of primary somatosensory cortex in mouse models of postoperative pain and inflammatory painPoster presentation
- 第41回日本神経科学大会, Jul. 2018, English, 神戸, Domestic conference術後痛モデルマウスにおける第一次体性感覚野のin vivoカルシウムイメージングPoster presentation
- 第5回イメージング数理研究会, Jul. 2018, Japanese, 神戸, Domestic conference術後痛モデルマウスにおける第一次体性感覚野 in vivo カルシウムイメージングPoster presentation
- 第41回日本神経科学大会, Jul. 2018, Japanese, 神戸, Domestic conference術後痛モデルマウスにおける第一次体性感覚野 in vivo カルシウムイメージングPoster presentation
- 日本麻酔科学会第64回学術集会, Jun. 2017, Japanese, 日本麻酔科学会, 神戸, Domestic conferenceThe impact of intraoperative end tidal CO2 with the incidence of postoperative nausea and vomitingPoster presentation
- The 63rd Annual Meeting of the Japanese Society of Anesthesiologists, May 2016, Japanese, 日本麻酔科学会, 博多, Domestic conferenceロボット支援腹腔鏡下前立腺全摘術における体温変化とシバリング発生に関する検討Poster presentation
- The 60th Annual Meeting of the Japanese Society of Anesthesiologists, May 2013, Japanese, The Japanese Society of Anesthesiologists, 札幌, Domestic conferenceEvaluation of cuffed tracheal tube size in children second reportPoster presentation
- The 59th Annual Meeting of the Japanise Society of Anesthesiologists, May 2012, Japanese, Japanese Society of Anesthesiologists, 神戸, 【目的】小児用カフ付き気管チューブ(CTT)Mallinckrodt Hi-Contourにおけるサイズ選択の指標について検討する。【方法】対象は全身麻酔下で挿管を要する0歳~4歳(ASA I-III)までの症例とし、チューブ選択は大容量低圧CTT(Microcuff)の有意性を示した報告(BJA 2009; 103: 867-873)をもとに、0ヶ月~7ヶ月:ID3.0、8ヶ月~1歳5ヶ月:ID3.5、1歳6ヶ月~2歳11ヶ月:ID4.0、3歳~4歳11ヶ月:ID4.5とした。気道内圧20(cmH2O、以下省略)にて(1)カフ圧0でのリーク有無、(2)カフ圧20でのリーク有無、(3)カフ圧≧60でのリーク有無、(4)リークが止まるカフ圧、さらに(5)従量式人工呼吸でのリーク量(=1-[一回換気量/(換気量設定値10mL/kg)])、(6)抜管後の合, Domestic conferenceEvaluation of cuffed tracheal tube size in childrenPoster presentation
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2025 - 31 Mar. 2028ミトコンドリア分裂因子Drp1に着目した神経障害性疼痛のメカニズム解明
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2024 - 31 Mar. 2027Mechanisms of pain chronicity focused on opioid receptor activation in immune cells.
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2024 - 31 Mar. 2027Pathophysiology of Fibromyalgia focusing on the mitochondrial function of satellite glial cells
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2023 - 31 Mar. 2026安静時functional MRIを用いた意識の可視化
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, Apr. 2023 - Mar. 2026, Coinvestigator副作用のない麻酔薬の開発を目的としたアセチルコリン受容体の分子構造解析
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2022 - 31 Mar. 2025The effects of beta-2 adrenaline receptor signals in macrophages on the prolonged postoperative pain
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2021 - 31 Mar. 2024Exploring of the role of IgG antibodies in Fibromyalgia syndrome本研究では複数の患者および健常者血清から精製分離されたIgGは、スウェーデンカロリンスカ研究所より譲渡されたものを使用した。 12週齢雌マウスに対し、健常者由来IgGおよび線維筋痛症患者由来IgGを脊髄クモ膜下投与し、疼痛閾値の評価および免疫組織染色によるIgGの局在分布を解析した。マウス個体への投与前に、フィルターを用いた濃縮精製および滅菌を行った。マウスへの脊髄クモ膜下投与後、1日後、4日後、7日後にvon Frey試験による疼痛評価を行った。健常者および患者由来IgGのいずれもコントロール(生食投与群)に比較して疼痛閾値が低下する傾向にあったが、健常者、患者群間では有意差は認めなかった。今後、IgG濃度等の検討が必要と考えられる。また免疫組織解析によって、脳には明らかな局在を認めなかったが、脊髄および後根神経節においては、患者由来IgGがグリア細胞に分布することが明らかとなった。 一方、我々はマウスから採取したミクログリア初代培養細胞において、線維筋痛症患者由来IgGが健常者由来IgGと比較して有意に局在が強いことを明らかとしてきたが、併せて患者由来IgG存在下に培養した後に遺伝子発現解析を行ったところ、炎症性サイトカイン、ケモカインの産生を促進する可能性が見出された。またヒトiPS細胞由来ミクログリア様細胞を患者IgG存在下に培養したところ、患者IgGが結合は有意であることを確認した。
- 学術研究助成基金助成金/基盤研究(C), Apr. 2018 - Mar. 2021, Principal investigatorCompetitive research funding
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, Apr. 2015 - Mar. 2018Development of a new therapy for different incurable pain by combination multiple pain suppression mechanismsIn this project, we studied it for developing a new therapy of incurable neuropathic pain by performing of combination multiple pain suppression mechanisms for different severe neuropathic pain animal models. We made inflammatory animal models, plantar incision models and nerve ligation models in this study periods. We confirmed that a proper model was finished by a behavior evaluation and performed the study that aimed at the development of the effective expression method of having made siRNA which made expression of the BDNF inhibited more effectively and the endorphin in the cultured cell in particular. We also made the hybrid gene with the NGF gene to make beta endorphine productive cells of the secretor and confirmed expression by ELISA in a cultured cell.
- 学術研究助成基金助成金/基盤研究(C), Apr. 2015 - Mar. 2018, Principal investigatorCompetitive research funding