神戸大学 · 医学研究科/医学部 · 教授

研究キーワードanesthesiology・cardiac anesthesia・perioperative fluid therapy・general anesthetics・postoperative hyponatremia・transcatheter aortic valve implantation・chronic pain and sleep・critical care hemodynamics

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• Subtype-specific modulation of inhibitory interneurons by general anesthetics2026 · Elsevier BV, 2026年03月, iScience, 29(3) (3), 115140 - 115140
• Improvement of sleep and pain with lemborexant administration in patients with chronic pain: a retrospective observational study.2021 · 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.
• Incidence of hyponatremia with different postoperative intravenous maintenance fluids: a single-center, prospective, randomized trial.2018 · PURPOSE: Patients undergoing surgery are prone to postoperative hyponatremia, which can lead to delirium. However, the optimal sodium concentration for postoperative maintenance fluids in adult patients is still unclear. Therefore, this study examined the incidence of hyponatremia and delirium in postoperative patients. METHODS: This was a single-center, non-blinded, randomized trial. The inclusion criteria for this study were age 20 years or older and elective head and neck cancer or esophageal cancer surgery between April 2018 and June 2023. Patients were randomly assigned to one of three groups based on the sodium concentration in the intravenous fluids administered after surgery: the 140 mmol/L sodium (Na140) group, the 77 mmol/L sodium (Na77) group, and the 35 mmol/L sodium (Na35) group. RESULTS: A total of 105 patients had complete data at the end of the study: Na140 group (n = 35), Na77 group (n = 32), and Na35 group (n = 38). The incidence of postoperative hyponatremia was 22.9% (8/35) in the Na140 group, significantly lower than in the Na77 group [56.3% (18/32)] and the Na35 group [60.5% (23/38)] (both p
• Perioperative serum syndecan-1 concentrations in patients who underwent cardiovascular surgery with cardiopulmonary bypass and its association with the occurrence of postoperative acute kidney injury: a retrospective observational study.2016 · BACKGROUND: Various factors can cause vascular endothelial damage during cardiovascular surgery (CVS) with cardiopulmonary bypass (CPB), which has been suggested to be associated with postoperative complications. However, few studies have specifically investigated the relationship between the degree of vascular endothelial damage and postoperative acute kidney injury (pAKI). The objectives of this study were to measure perioperative serum syndecan-1 concentrations in patients who underwent CVS with CPB, evaluate their trends, and determine their association with pAKI. METHODS: This was a descriptive and case‒control study conducted at the National University Hospital. Adult patients who underwent CVS with CPB at a national university hospital between March 15, 2016, and August 31, 2020, were included. Patients who were undergoing preoperative dialysis, had preoperative serum creatinine concentrations greater than 2.0 mg dl-1, who were undergoing surgery involving the descending aorta were excluded. The perioperative serum syndecan-1 concentration was measured, and its association with pAKI was investigated. RESULTS: Fifty-two patients were included. pAKI occurred in 18 (34.6%) of those patients. The serum syndecan-1 concentration increased after CPB initiation and exhibited bimodal peak values. The serum syndecan-1 concentration at all time points was significantly elevated compared to that after the induction of anesthesia. The serum syndecan-1 concentration at 30 min after weaning from CPB and on postoperative day 1 was associated with the occurrence of pAKI (OR = 1.10 [1.01 to 1.21], P = 0.03]; OR = 1.16 [1.01 to 1.34], P = 0.04]; and the cutoff values of the serum syndecan-1 concentration that resulted in pAKI were 101.0 ng ml-1 (sensitivity = 0.71, specificity = 0.62, area under the curve (AUC) = 0.67 (0.51 to 0.83)) and 57.1 ng ml-1 (sensitivity = 0.82, specificity = 0.56, AUC = 0.71 (0.57 to 0.86)). Multivariate logistic regression analysis revealed that the serum syndecan-1 concentration on postoperative day 1 was associated with the occurrence of pAKI (OR = 1.02 [1.00 to 1.03]; P = 0.03). CONCLUSION: The serum syndecan-1 concentration at all time points was significantly greater than that after the induction of anesthesia. The serum syndecan-1 concentration on postoperative day 1 was significantly associated with the occurrence of pAKI. TRIAL REGISTRATION: This study is not a clinical trial and is not registered with the registry.

• 神経栄養因子の発現調節による術後認知機能障害の予防と治療 小幡 典彦 日本学術振興会, 学術研究助成基金助成金／基盤研究(C), 基盤研究(C), 神戸大学, 2017年04月 - 2020年03月, 研究代表者 本研究では2型糖尿病モデルマウスを用いて周術期の行動変化および脳内での神経栄養因子を含めた各種mRNA発現量変化について調査した。 2型糖尿病モデルマウスは高脂肪食を摂食させ作製した。行動はオープンフィールド、新奇物体認識試験、明暗箱試験を含む一連のプロトコールにより評価を行い、手術侵襲として開腹手術を施行した。行動実験後、脳組織（前頭葉皮質）を採取し、real-time PCRを用いて神経栄養因子やカテコラミン受容体などのmRNA発現量について解析した。 2型糖尿病モデルマウスでは術後に活動性の低下がみられ、脳内の神経栄養因子やカテコラミンの発現変化が影響している可能性が示唆された。 競争的資金2017 · KUID parsed section
• アデノ随伴ウィルスベクターを用いた神経障害性痛に対する遺伝子治療 小幡 典彦 日本学術振興会, 科学研究費助成事業, 若手研究(B), 神戸大学, 2013年04月01日 - 2015年03月31日, 研究代表者 本研究の目的は、痛みに関わる神経伝達に重要な役割を果たすとされる脳由来神経栄養因子(BDNF)遺伝子に注目し、アデノ随伴ウィルス(AAV)ベクターを用いて痛み発生メカニズムに寄与するBDNFの発現抑制を実現することで、難治性疼痛の新たな治療法を確立することである。 まず、痛みに関わる特異的なBDNFの発現を阻害するRNAを組み込んだAAVベクターを作成した。次に、痛み動物モデルにおいて脊髄くも膜下腔内に作成したAAVベクターを投与し、神経節におけるBDNF合成阻害を確認し、その鎮痛効果を検討する。最終的には本治療法の安全性を確認し、臨床における治療法開発への道を探る。 競争的資金2013 · KUID parsed section
• 遺伝子多型ペースメーカーチャンネルによる細胞内伝達抑制を用いた慢性痛遺伝子治療 賀来 隆治, 小幡 典彦 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 岡山大学, 2013年04月01日 - 2016年03月31日 急性痛から慢性痛への移行機序として、神経障害部位へのペースメーカーチャンネルの集積が報告されている。遺伝子多型ペースメーカーチャンネルは細胞膜に存在しても電流を流さないため、神経障害部位に強発現させることにより、異所性放電を抑制できる可能性がある。本研究では、細胞内サイクリックAMPを制御することにより、細胞膜へのペースメーカーチャンネル発現を抑制し、それが疼痛行動抑制につながることを明らかにした。本現症と同様の働きをもつ遺伝子多型チャンネルの障害部位への導入が痛みに与える影響については今後の検討が必要である。2013 · KUID parsed section
• 脳由来神経栄養因子に対するDNAデコイによる疼痛制御の基礎的研究 横山 正尚, 小幡 典彦, 松岡 義和 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 高知大学, 2009年 - 2011年 神経障害性痛モデルの脊髄レベルで、特異的に過剰に発現する脳由来神経栄養因子(BDNF)のエクソン-1に対するDNAデコイを作成した。疼痛モデルの脊髄レベルにおいてBDNFエクソン-1をノックダウンするために、作成したDNAデコイを脊髄内投与し、炎症痛モデルおよび神経障害性痛モデルで痛み反応の減弱を確認した。2009 · KUID parsed section

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