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NOMURA YukiUniversity Hospital / Anesthesiology and Pain ClinicAssociate Professor
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■ Paper- 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
- (一社)日本小児麻酔学会, Oct. 2018, 日本小児麻酔学会誌, 24(Suppl.) (Suppl.), 188 - 188, Japanese
- 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
- (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
- 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
- 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. 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
- 学術研究助成基金助成金/基盤研究(C), Apr. 2015 - Mar. 2018, Principal investigatorCompetitive research funding