Published papers

Background. The biopsychosocial mechanism by which exercise leads to improvement in chronic low back pain (CLBP) remains unstudied. This prospective cohort study was performed to examine the effectiveness of exercise on pain, disability, and psychological status for CLBP. We also tested path analytic models in which changes in these variables were included. Methods. CLBP patients who visited the Interdisciplinary Pain Center of Keio University Hospital from July 2018 to April 2020 were included. The propensity score matching was performed between patients who underwent exercise (the exercise group) and those who did not (the control group). At the first visit and at the 3-month follow-up, pain (Numerical Rating Scale (NRS)), disability (Pain Disability Assessment Scale (PDAS)), and psychological status (Pain Self-Efficacy Questionnaire (PSEQ), and Pain Catastrophizing Scale (PCS)) were assessed. Changes in pain and disability at the follow-up were compared between the groups. The relationships between changes in pain, disability, and psychological variables were examined using Pearson’s correlation and mediation analysis. Results. A significantly larger decrease in the PDAS was observed in the exercise group (N = 49) than in the control (N = 49) (p<0.05). Increased PSEQ scores were significantly correlated with decreased NRS scores in both groups. In the exercise group, decreased PDAS fully mediated the relationship between increased PSEQ and decreased NRS (P<0.05). Conclusion. Exercise improved disability, and the improved disability by exercise mediated the effect of increased self-efficacy on pain relief in CLBP patients.

Exercise is associated with lower prevalence and severity of pain, and is widely recommended for pain management. However, the mechanisms the exercise effect on pain remain unclear. In this study, we examined the association of exercise with pain and aimed to identify its neurobiological mediators. We utilized a baseline data of a clinical trial for people with low back pain. Participants reported pain intensity and exercise habit, as well as pain-related psychological and emotional assessments. We also obtained brain imaging data using a resting-state functional MRI and performed mediation analyses to identify brain regions mediating the exercise effect on pain. Forty-five people with low back pain (mean pain intensity = 59.6 and mean duration = 9.9 weeks) were included in this study. Participants with an exercise habit (n = 29) showed significant less pain compared to those without an exercise habit (n = 16). Mediation analysis using resting-state functional connectivity identified the left thalamus, right amygdala, and medial prefrontal cortex as statistical mediators of the exercise effect on pain (indirect effect = -0.460, 95% confidence interval = -0.767 to -0.153). In conclusion, our findings suggest that brain function of the specific regions is probably a neuro-mechanism of exercise alleviating pain.

Lumbar disc herniation (LDH) is a common back disorder that evokes back and/or leg pain. Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive surgery for patients with LDH. However, there is little evidence of effectiveness of PELD compared with conservative treatments. Objective: The goal of this study was to quantify the efficacy of PELD compared with conservative treatments. Methods: Here, we conducted a prospective observational cohort study using momentary pain assessments via a smartphone app during 3 months following surgery. The trajectories of daily ecological momentary pain assessments were fitted with an exponential model containing two parameters: a pain reduction coefficient and the percentage of persistent pain. To control for selection bias between PELD and Conservative groups (N = 167 and 34), we used inverse probability (IP) of treatment weighting for statistical comparisons. Results: Compared with conservative treatments, both momentary pain rating and the exponential model showed statistically significant pain recovery following PELD (p < 0.001). In addition, PELD had a faster pain recovery rate (hazard ratio (95% confidence interval): 1.75 (1.40, 2.20), p < 0.001), greater overall pain recovery rate (odds ratio (95%CI): 2.35 (2.01, 5.26), p < 0.001), faster pain reduction (t199 = 3.32, p = 0.001), and lower estimated persistent pain (Z = 2.53, p = 0.011). Greater pain intensity and lower anxiety before the surgery were predictors of faster pain reduction in the recovery subgroup following PELD. Conclusions: In conclusion, momentary pain rating and the model fitting revealed that PELD provided rapid pain recovery that lasted for at least three months. Greater pain intensity and lower anxiety before the surgery were predictors of faster pain reduction in the recovery subgroup following PELD. Daily momentary pain rating on a smartphone may be able to provide more informative data to evaluate effect of an intervention than pain assessment on hospital visits.

目的:就労環境における慢性痛の実態、及び慢性痛が仕事に影響する重症例でのリスク因子を明らかにする。対象と方法:大手製造業A社の首都圏にある1事業所、上記とは別の大手製造業B社の関西圏にある1事業所、及び大手小売業C社の関西圏にある16店舗、計3社18施設の被雇用者を対象に、「からだの痛みに関する調査研究アンケート」を施行した。A社B社では参加者の同意を得たうえでアンケートデータと企業健診の問診データを突合し、基本集計を行うと共に、対象者の生活習慣や心理社会的因子と慢性痛有症との関連について、性年齢調整ロジスティック回帰分析を用いて分析した。結果:調査対象2,544名のうち1,914名(男性1,224名、女性690名)から有効回答が得られた(有効回答率75.2%)。3ヵ月以上持続する慢性痛を有するものは全解析対象者の42.7%であり、仕事に影響する慢性痛を有するものは全解析対象者の11.3%であった。痛みのない群と比較して、仕事に影響する慢性痛群は、肥満、喫煙習慣、不眠症、ワーカホリック度の高さ、上司・同僚からの支援の乏しさ、仕事の満足度の低さ、仕事の要求度の高さ、仕事のコントロール度の低さ、心理的ストレスの高さ、抑うつ状態と有意に関連があった。考察と結論:就労環境における慢性痛とそのリスク因子の実態が一部明らかとなった。産業衛生分野において健康関連リスク因子として重要視されてきた、肥満、喫煙、不眠症、職場環境、心理的ストレス、抑うつは職場の慢性痛対策をおこなう上でも重要であることが示唆された。(著者抄録)

「痛み」と「報酬」は、我々の脳で相反する刺激として認知され、その関係性を理解することは痛み医療において重要である。しかしながら、脳内報酬系には様々な役割があり、痛みとの関連性を理解することは簡単ではない。本稿では報酬系の機能を報酬認知、鎮痛効果、報酬予測、強化学習の4つに分類し、それぞれの役割における痛みとの関連性について概説する。痛みは報酬認知を歪め、慢性痛患者では報酬系の機能低下が生じている。報酬系の活性化は鎮痛効果を惹起できるが、痛みにより衝動性が高まっている状態では不適切な学習により痛みの悪循環に陥りやすいと考えられる。慢性痛医療においては、認知の歪みや報酬系の機能低下を患者個人のレベルで評価し、持続的な報酬系の活性化につながるような適切な医療を段階的に提供していく姿勢が求められる。今後、慢性痛医療にとって重要な「痛みと報酬系の関係」について臨床的な研究が進むことが期待される。(著者抄録)

Background: Few prospective study examined the optimal postoperative opioid dose setting for chronically opioid consuming patients. We prospectively investigated whether postoperative pain control based on the equianalgesic conversion of the preoperative opioid dose is a safe and adequate way of relieving postoperative pain in patients with chronic opioid use. Methods: The patients were allocated into the high dose group (HG) or the low dose group (LG) according to their preoperative doses of opioid. After surgery, the patients received intravenous morphine using a patient-controlled analgesia (PCA) pump which was set based on their preoperative opioid dose. The numerical rating scale (NRS) pain score, 24 hr cumulative morphine consumption, and the incidence of adverse events were compared between the groups. Results: A total of seventeen patients (HG I n=9, LG; n=8) were enrolled. The worst NRS pain score was significantly higher in HG than in LG. No serious adverse events due to overdose occurred in either group. Conclusions: Our PCA regimen appears to be safe overall; however it is still inadequate for relieving postoperative pain in patients taking high preoperative opioid doses.

INTRODUCTION: Pain is known to have a high impact on work performance, but there are several confounding factors, such as stress and mental issues. Little is known about the impact of pain severity on work performance when adjusted for such confounding factors. The aim of this study was to identify the effect of pain severity on absence from work (absenteeism) and reduced performance (presenteeism). METHODS: A cross-sectional study was conducted among full-time workers at an industrial manufacturing company in Japan. Participants were assessed using a self-reported questionnaire, including work performance evaluations, pain characteristics, pain-related fear, psychological distress, stress at the workplace and home, workaholism, and self-awareness. Principal component analysis was utilized to decrease the dimensions of the measures, and orthogonal rotation was performed on identified components with an eigenvalue > 1.0. Multivariable logistic regression analyses were performed to determine the association between pain severity and absenteeism and presenteeism, and were adjusted for confounding factors. We also analyzed the association between pain intensity and presenteeism using multivariable logistic regression analyses. RESULTS: A total of 349 workers participated in the study. Six principal components were identified as confounding factors: work stress, regulation, mental instability, less support, home stress, and life dissatisfaction. Multivariable logistic regression analyses showed significant associations of moderate to severe pain with absenteeism (p = 0.02) and low and high presenteeism (p = 0.004 and 0.009, respectively), adjusted for age, sex, body mass index, short sleep, and the six principal components. Pain intensity was also significantly associated with low and high presenteeism (p = 0.002 and 0.014, respectively) in people with pain. CONCLUSIONS: Pain severity is a risk factor for absenteeism and presenteeism, even if workers have comorbid psychological stress or mental health problems.

PURPOSE: We aimed to investigate the effect of repeated transforaminal epidural low-dose dexamethasone injections on glucose profiles and pituitary-adrenal axis functions of diabetic and non-diabetic patients with low back pain. METHODS: A total of 28 patients (ten diabetic [DM group] and 18 non-diabetic patients [non-DM group]) with low back pain were followed-up. Transforaminal epidural low-dose dexamethasone (1.65 mg) injections were repeated every 7-14 days for 8 weeks. Fasting blood sugar (FBS), hemoglobin A1c (HbA1c), morning plasma adrenocorticotropin (ACTH), and cortisol levels were measured at baseline and during the 8-week follow-up period. RESULTS: There were no significant changes in FBS and HbA1c levels between baseline and 8-week follow-up period in both DM and non-DM groups (difference in FBS [95% confidence Interval, CI]: - 0.6 mg/dL [- 6.4, 5.1], p = 0.83 in the non-DM group, - 0.2 mg/dL [- 26.2, 25.8], p = 0.99 in the DM group; difference in HbA1c [95% CI] - 0.02% [- 0.1, 0.1], p = 0.69 in the non-DM group, 0.04% [- 0.3, 0.4], p = 0.79 in the DM group). There were no significant longitudinal changes in ACTH and cortisol levels (ACTH, p = 0.38 [baseline vs. 8 week], p = 0.58 [non-DM vs. DM]; cortisol, p = 0.52 [baseline vs. 8 week], p = 0.90 [non-DM vs. DM]). CONCLUSIONS: Repeated transforaminal epidural low-dose dexamethasone injections provided no significant elevations in blood glucose or suppression of the pituitary-adrenal axis for two months from the first injection in both diabetic and non-diabetic patients. Our results indicate the intermediate-term safety of repeated transforaminal epidural low-dose dexamethasone injections with regard to the effect on glucose profile and pituitary-adrenal axis functions.

Abstract Purpose This study aimed to investigate whether smoking is an independent risk factor for central sensitization syndrome (CSS) in individuals with pain as measured by the Central Sensitization Inventory (CSI). Methods In 2020, we conducted an Internet survey targeting 2000 ordinary residents of Japan (aged 20–69 years) who had pain symptoms from October to November 2020. A multiple regression analysis was performed on the association between smoking status (nonsmokers and current smokers; Brinkman index) and CSI values. Moreover, compared to nonsmokers, the relative risk (RR) of the CSI cut-off score of 40 points or higher among current smokers was calculated using a modified Poisson regression model. Covariates included age, sex, body mass index, marital status, equivalized income, exercise habits, history of hypertension, history of hyperlipidemia, history of diabetes, pain chronicity, and Pain Catastrophizing Scale score. Results This study analyzed 1,822 individuals (1,041 men and 781 women). Among those experiencing pain, current smoking was associated with the increase in CSI values (β = 0.07). The Brinkman index was also significantly associated with the increase in CSI values (β = 0.06). Current smoking also increased the risk of being over the CSI cut-off score, with a relative risk (RR) of 1.29 (95% confidence intervals, 1.04–1.60). Younger age, being women, experiencing chronic pain, and higher pain catastrophizing thinking were also significantly associated with increased CSS severity, independent of smoking status. Conclusion Smoking is an independent risk factor for CSS. This indicates that smoking may be an important factor in the management of central pain disorders.

Interoceptive awareness, the conscious perception of internal bodily states, is a key construct of mind-body interaction. Decreases in interoceptive awareness, as measured by the Multidimensional Assessment of Interoceptive Awareness (MAIA), are found in chronic pain patients. In this study, we explored whether a specific aspect of interoceptive awareness is a risk for the onset and chronicity of pain. A longitudinal cohort study was conducted in 2018 and 2020 among a sample of full-time workers in an industrial manufacturing company in Japan. Participants completed a questionnaire on pain intensity, MAIA, exercise habits, kinesiophobia, psychological distress and work stress. Principal component analyses using the MAIA identified two principal components: self-control and emotional stability. Low emotional stability was associated with the prevalence of moderate to severe pain in 2020 among people with mild or no pain in 2018 (p < 0.01). Lack of exercise habits were associated with the prevalence of moderate to severe pain in 2020 among people with pain in 2018 (p < 0.01). Furthermore, exercise habits were associated with reduction in kinesiophobia among people with moderate to severe pain in 2018 (p = 0.047). Overall, these findings indicate that low emotional stability may be a risk for the onset of moderate to severe pain; lack of exercise habits may sustain kinesiophobia and be a risk for the chronicity of pain.

Pain is a global health problem that leads to sedentary behavior and tends to cause negative emotion. In contrast, exercise is widely recommended for a health promotion, while pain often worsens with physical activity. Although exercise therapy is often prescribed to people with pain, the mechanisms of exercise effect on pain remains unclear. In this study, we tried to identify a universal association factor between regular exercise and pain intensity utilizing a cross-sectional web-based survey involving 52,353 adult participants from a large national study conducted in Japan. Using principal component analysis, we uncovered a mediation model of exercise effect on pain through psychological components. Analyses were performed in half of the population with pain (n = 20,330) and validated in the other half (n = 20,330), and showed that high-frequency exercise had a significant association with reduction in pain intensity. We also found Negative Affect and Vigor, two psychological components, are fully associating the exercise effect on pain (indirect effect = − 0.032, p < 0.001; association proportion = 0.99) with a dose-dependent response corresponding to the frequency of exercise. These findings were successfully validated (indirect effect of high-frequency exercise = − 0.028, p < 0.001; association proportion = 0.85). Moreover, these findings were also identified in subpopulation analyses of people with low back, neck, knee pain, and the tendency of the exercise effect on pain was increased with older people. In conclusion, the effect of exercise on pain is associated with psychological components and these association effects increased in parallel with the frequency of exercise habit regardless pain location.

Abstract Aim The coronavirus disease 2019 (COVID‐19) pandemic has caused unprecedented stress. Mindfulness‐based interventions (MBIs) are known to be effective in reducing stress. However, it is unclear how long‐term outcomes differ between those who continue mindfulness practice after MBIs and those who do not. In this study, we hypothesized that those who continued mindfulness practice would have higher stress tolerance, and we examined this hypothesis through a survey of MBI graduates. In this study, we examined the association between the continuation of mindfulness practice among MBI completers and individual stress during the COVID‐19 epidemic. Methods A cross‐sectional survey of MBI graduates was conducted. The physical and mental health states were compared between those who established a habit of mindfulness practice (practice group) and those who did not (no practice group). Results The data were collected from 95 participants (response rate: 53.7%). Of the total respondents, 66 (69.5%) practiced mindfulness. Although the degree of perceived stress due to the COVID‐19 pandemic was not statistically different between the practice and no practice groups, the practice group showed significantly lower levels of depression (p = 0.007), higher levels of resilience (p = 0.006), higher levels of overall health (p = 0.006), and higher levels of mental health (p = 0.039). The effect of mindfulness practice on reducing depression was fully mediated by resilience. Conclusion Among MBI graduates, those who regularly practiced mindfulness had lower levels of depression and higher levels of physical and mental health. Thus, the continuation of mindfulness practice increases resilience, buffers against new stressors such as the COVID‐19 pandemic, and has the potential to prevent depression.

脊椎疾患の保存的治療における疼痛および障害の改善に影響する因子を縦断的に調査した.施設倫理委員会承認後,2018年7月〜2019年12月に当センターを受診した18歳以上の脊椎疾患患者185名を解析した.患者背景(年齢・性別・body mass index・罹患期間・罹患高位・脊椎手術歴),治療因子(内服・神経ブロック・運動療法),および初診時・3ヵ月後の簡易疼痛質問票(BPI),疼痛生活障害尺度(PDAS),不安抑うつ尺度(HADS),痛みの破局化思考(PCS)を調査した.3ヵ月後の疼痛および障害の改善は,BPI減少率≧50%およびPDAS減少率≧30%と定義した.短い罹患期間および神経ブロック治療が疼痛改善と有意に関連した(p<0.05).若年齢,短い罹患期間,および脊椎手術歴がないことが障害改善と有意に関連した(p<0.05).3ヵ月間のHADSおよびPCSの変化量は,BPIおよびPDASの変化量と有意に相関した(p<0.001).脊椎疾患の保存的治療では,早期介入や局所鎮痛がアウトカム改善に寄与するが,高齢者や脊椎手術既往者では治療反応性は乏しく,治療内容の再考を要する.(著者抄録)

疼痛患者の抱える「不公平感」は症状の遷延や重篤化につながる。今回、12項目から構成される不公平感質問票を、より簡便に利用できるように開発された短縮版不公平感質問票(Injustice Experience Questionnaire-Short Form:IEQ-SF)の言語的妥当性を担保した日本語版を作成した。IEQ-SFは5つの質問項目と3つの選択肢から構成される。言語的に妥当な尺度の翻訳版を作成するための国際的なガイドライン、およびIEQ-SFの著作権管理会社が定めるガイドラインに準拠した手続きを経て、国際比較研究に使用できる水準の日本語版が作成できた。(著者抄録)

We investigated the association of chronic low back and neck pain classification based on ICD-11 with pain relief under interdisciplinary pain management. A total of 212 patients with chronic musculoskeletal pain, who visited the Interdisciplinary Pain Center of Keio University Hospital, were categorized into chronic primary musculoskeletal pain (CPMP), chronic secondary musculoskeletal pain, and chronic neuropathic pain (CNP) groups based on ICD-11 and followed-up. We assessed pain intensity using the Brief Pain Inventory (BPI) at the first visit and at 3 months. Improvement of pain was defined as ≥30％ reduction in the BPI. Multivariate logistic regression analysis revealed that CNP were significantly associated with a greater improvement of pain after adjusting for sex, age, duration of pain, level of pain self-efficacy, and treatment options. [odds ratio (CNP/CPMP) (95％ confidence interval); 2.52 (1.25–5.09, p＝0.02)]. We concluded that the ICD-11 code for chronic low back and neck pain is significantly associated with pain treatment outcomes.

難治性の低血圧、徐脈、低血糖をきたし、ステロイド投与により劇的に症状改善を認めた症例を経験した。症例は78歳、男性。今回、残胃癌に対して手術が施行された。術後経過は概ね良好であったが、術後2ヵ月にショック状態となり、ICU入室、挿管人工呼吸、全身管理が必要となった。低血圧、徐脈に対し、輸液、輸血、カテコラミン投与、低血糖に対し、ブドウ糖を適宜投与した。カテコラミン抵抗性循環不全および低血糖から急性副腎不全を疑い、診断的治療を兼ねてハイドロコルチゾンを静注したところ、数時間で循環動態および低血糖は改善、カテコラミンの速やかな減量が可能となり、その後の経過は良好であった。本症例はステロイド投与歴もなく、カテコラミン抵抗性の循環不全、低血糖をきたした。このような症例では、既往や明らかな誘因がない場合でも副腎不全を疑う必要がある。(著者抄録)

慢性痛に対する認知行動療法の効果を明らかにするため、実施用のマニュアルを作成した後にパイロット研究を実施した。産業界における慢性痛の実態調査と認知行動療法の需要を調べるために、3つの企業に従事する労働者を対象にアンケート調査を実施した。短期入院プログラムを実施し、その効果が高いことを確認した。認知行動療法を普及させる基礎を作るために、各医療者向けの痛みの教育コンテンツやコアカリキュラムを製作した。(著者抄録)

腹側被蓋野から側坐核へ投射するドパミン神経は脳報酬系の主要なネットワークである。われわれは薬理遺伝学的手法によるこの神経の特異的な抑制により、運動による除痛効果が減弱することを報告した。運動療法は報酬系の活性化を伴って身体機能、行動、脳機能の3つの障害を総合的に改善しうる。加えて、コーチングによる報酬系活性化は運動療法の強化と習慣化に寄与すると考えられ、慢性痛治療の新しい方向性になると期待できる。(著者抄録)