研究者詳細 - 若泉　謙太

論文 - 若泉　謙太

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Exercise effect on pain is associated with negative and positive affective components: A large-scale internet-based cross-sectional study in Japan

Wakaizumi K., Shinohara Y., Kawate M., Matsudaira K., Oka H., Yamada K., Jabakhanji R., Baliki M.N.

Scientific Reports （Scientific Reports） 14 （ 1 ） 2024年12月

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.

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Association between smoking and central sensitization pain: a web-based cross-sectional study

Chiba S., Yamada K., Kawai A., Hamaoka S., Ikemiya H., Hara A., Wakaizumi K., Tabuchi T., Yamaguchi K., Kawagoe I., Iseki M.

Journal of Anesthesia （Journal of Anesthesia） 38 （ 2 ） 198 - 205 2024年04月

ISSN 09138668

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.

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Impact of continued mindfulness practice on resilience and well-being in mindfulness-based intervention graduates during the COVID-19 pandemic: A cross-sectional study

Tanaka C., Wakaizumi K., Ninomiya A., Tamura N., Kosugi S., Park S., Sado M., Mimura M., Fujisawa D.

Psychiatry and Clinical Neurosciences Reports （Psychiatry and Clinical Neurosciences Reports） 2 （ 3 ） 2023年09月

査読有り, ISSN 2769-2558

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.

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Effect of repeated transforaminal epidural low-dose dexamethasone injections on glucose profiles of diabetic and non-diabetic patients with low back pain

Hoshino R., Wakaizumi K., Otsuka Y., Morisaki H., Kosugi S.

Journal of Anesthesia （Journal of Anesthesia） 37 （ 2 ） 261 - 267 2023年04月

査読有り, ISSN 09138668

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.

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Decreased Interoceptive Awareness as a Risk Factor for Moderate to Severe Pain in Japanese Full-Time Workers: A Longitudinal Cohort Study

Takaoka S., Wakaizumi K., Tanaka C., Tanaka S., Kawate M., Hoshino R., Matsudaira K., Fujisawa D., Morisaki H., Kosugi S.

Journal of Clinical Medicine （Journal of Clinical Medicine） 12 （ 8 ） 2896 - 2896 2023年04月

責任著者, 査読有り

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.

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Influence of exercise on pain is associated with resting-state functional connections: A cross-sectional functional brain imaging study

Wakaizumi K., Reckziegel D., Jabakhanji R., Apkarian A.V., Baliki M.N.

Neurobiology of Pain （Neurobiology of Pain） 13 100125 - 100125 2023年01月

査読有り

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.

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A Cross-Sectional Study of the Impact of Pain Severity on Absenteeism and Presenteeism Among Japanese Full-Time Workers

Tanaka C., Wakaizumi K., Takaoka S., Matsudaira K., Mimura M., Fujisawa D., Kosugi S.

Pain and Therapy （Pain and Therapy） 11 （ 4 ） 1179 - 1193 2022年12月

査読有り, ISSN 21938237

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.

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痛みとタバコ;ステートメントを超えて beyond the statement 日本の疫学研究からみえる喫煙と疼痛の関係

山田恵子, 千葉聡子, 若泉謙太, 井関雅子, 田淵貴大

PAIN RESEARCH （(一社)日本疼痛学会） 37 （ 4 ） 190 - 190 2022年12月

ISSN 0915-8588

集学的痛みセンターにおける慢性腰痛・頚部痛の治療反応性―ICD-11に基づく慢性痛分類による比較―

星野麗子, 本田あやか, 篠原佑太, 石川愛子, 田中智里, 辻収彦, 若泉謙太, 森崎浩, 小杉志都子

日本ペインクリニック学会誌（一般社団法人日本ペインクリニック学会） 29 （ 9 ） 187 - 192 2022年09月

査読有り, ISSN 1340-4903

【目的】本研究では，国際疾病分類（ICD-11）に基づいて慢性腰痛および慢性頚部痛を分類し，ICD-11の慢性痛分類コードと集学的治療下での疼痛改善との関連を調べた．【方法】当施設倫理委員会承認後，慢性腰痛および頚部痛を主訴に当院集学的痛み診療センターを受診した212人をICD-11に基づき一次性筋骨格系疼痛，二次性筋骨格系疼痛，および神経障害性疼痛に分類した．個々の症例は集学的評価に基づいて治療介入を行った．3カ月後の痛みの強さ（Brief Pain Inventory）が初診時の30％以上減少した場合を疼痛改善と定義した．多変量ロジスティック回帰分析を用いて，患者特性，治療因子，ならびにICD-11の慢性痛分類コードと疼痛改善の関連を調べた．【結果】神経障害性疼痛は，一次性筋骨格系疼痛と比較し，3カ月後の疼痛改善に対するオッズ比が有意に高かった［オッズ比（95％信頼区間）2.52（1.25～5.09），p＝0.02］．【結語】集学的治療下における慢性腰痛および頚部痛の疼痛改善に対して，ICD-11による慢性痛分類は重要な関連因子となりうる．

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Negative effect of anger on chronic pain intensity is modified by multiple mood states other than anger: A large population-based cross-sectional study in Japan

Yamada K., Fujii T., Kubota Y., Wakaizumi K., Oka H., Matsudaira K.

Modern Rheumatology （Modern Rheumatology） 32 （ 3 ） 650 - 657 2022年05月

査読有り, ISSN 14397595

Objectives: To investigate whether mood states other than anger can modify the association between anger and pain intensity in individuals with chronic pain. Methods: We analysed 22,059 participants with chronic pain, including 214 participants with rheumatoid arthritis (RA), who completed a questionnaire. The Profile of Mood States short form (POMS-SF) was used to assess six dimensions of mood states (anger-hostility, tension-anxiety, depression-dejection, confusion, fatigue, and vigour). A numerical rating scale (NRS) assessed pain intensity. We examined the association between anger-hostility and the NRS and the relationship between POMS-SF components. Moderation analyses were used to investigate whether the five mood states other than anger-hostility modified the effect of anger-hostility on the NRS. Results: Anger-hostility contributed to pain intensity. Although increased mood states other than vigour were associated with increased pain intensity, these increased mood states appeared to suppress the effect of anger-hostility on pain intensity. Increased vigour was associated with decreased pain intensity and increased the effect of anger-hostility on pain intensity. Conclusions: Mood states other than anger may influence the association between anger and pain intensity in individuals with chronic pain. It is important to focus on complicated mood states and anger in individuals with chronic pain, including RA.

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Effects of Thoracic Epidural Anesthesia on Systemic and Local Inflammatory Responses in Patients Undergoing Lung Cancer Surgery: A Randomized Controlled Trial

Okuda J., Suzuki T., Wakaizumi K., Kato J., Yamada T., Morisaki H.

Journal of Cardiothoracic and Vascular Anesthesia （Journal of Cardiothoracic and Vascular Anesthesia） 36 （ 5 ） 1380 - 1386 2022年05月

査読有り, ISSN 10530770

Objective: Inflammatory responses play major roles in the development of acute lung injury following lung cancer surgery. The authors tested the hypothesis that thoracic epidural anesthesia (TEA) during surgery could attenuate both systemic and local inflammatory cytokine productions in patients undergoing lung cancer surgery. Design: A prospective randomized controlled trial. Setting: At Keio University Hospital, Tokyo, Japan. Participants: Patients scheduled for lung cancer surgery. Interventions: Sixty patients were randomly allocated into two groups (n = 30 each group): the epidural group (group E), in which anesthesia was maintained with propofol, fentanyl, rocuronium, and epidural anesthesia with 0.25% levobupivacaine; or the remifentanil group (group R), in which a remifentanil infusion was used as a potent analgesia instead of epidural anesthesia. Measurements and Main Results: The lung epithelial lining fluid (ELF) and blood sampling were collected prior to one-lung ventilation (OLV) initiation (T1) and at 30 minutes after the end of OLV (T2). The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the ELF at T2 were increased significantly compared with those at T1 in both groups. The ELF concentration of IL-6 in group E was significantly lower than that in group R at T2 (median [interquartile range]: 39.7 [13.8-80.2] versus 76.1 [44.9-138.2], p = 0.008). Plasma IL-6 concentrations at T2, which increased in comparison to that at T1, were not significantly different between the two groups. The plasma concentrations of TNF-α did not change in both groups. Conclusions: This randomized clinical trial suggested that TEA could attenuate local inflammatory responses in the lungs during lung cancer surgery.

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Improvement in Disability Mediates the Effect of Self-Efficacy on Pain Relief in Chronic Low Back Pain Patients with Exercise Therapy

Shinohara Y., Wakaizumi K., Ishikawa A., Ito M., Hoshino R., Tanaka C., Takaoka S., Kawakami M., Tsuji O., Fujisawa D., Fujiwara T., Tsuji T., Morisaki H., Kosugi S.

Pain Research and Management （Pain Research and Management） 2022 1 - 8 2022年

査読有り, ISSN 12036765

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.

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痛みによる報酬行動の変化と脳科学的メカニズム

若泉謙太

慢性疼痛（日本慢性疼痛学会） 40 （ 1 ） 68 - 75 2021年12月

筆頭著者, 最終著者, 責任著者, 査読有り, ISSN 1340-2331

「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)

Loneliness, social isolation, and pain following the COVID-19 outbreak: data from a nationwide internet survey in Japan

Yamada K., Wakaizumi K., Kubota Y., Murayama H., Tabuchi T.

Scientific Reports （Scientific Reports） 11 （ 1 ） 18643 - 18643 2021年12月

査読有り

The aim of cross-sectional study was to investigate the association between loneliness, increased social isolation, and pain following the COVID-19 outbreak. A total of 25,482 participants, aged 15–79 years, were assessed using an internet survey; the University of California, Los Angeles Loneliness Scale (Version 3), Short Form 3-item (UCLA-LS3-SF3) was used to assess loneliness, and a modified item of the UCLA-LS3-SF3 was used to measure the perception of increased social isolation during the pandemic. The outcome measures included the prevalence/incidence of pain (i.e., headache, neck or shoulder pain, upper limb pain, low back pain, and leg pain), pain intensity, and the prevalence of past/present chronic pain. Pain intensity was measured by the pain/discomfort item of the 5-level version of the EuroQol 5 Dimension scale. Odds ratios of pain prevalence/incidence and past/present chronic pain prevalence according to the UCLA-LS3-SF3 scoring groups (tertiles) and the frequency of the perceived increase in social isolation (categories 1–5) were calculated using multinomial logistic regression analysis. The mean pain intensity values among different loneliness and social isolation levels were tested using an analysis of covariance. Increased loneliness and the severity of the perceived social isolation were positively associated with the prevalence/incidence of pain, pain intensity, and the prevalence of past/present chronic pain.

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新型コロナウイルスの蔓延と仕事のパフォーマンスの変化 JACSIS研究より

若泉謙太, 山田恵子, 島津明人, 田淵貴大

臨床麻酔（真興交易(株)医書出版部） 45 （ 12 ） 1565 - 1572 2021年12月

筆頭著者, 責任著者, ISSN 0387-3668

Sex-Specific Pharmacotherapy for Back Pain: A Proof-of-Concept Randomized Trial

Reckziegel D., Tétreault P., Ghantous M., Wakaizumi K., Petre B., Huang L., Jabakhanji R., Abdullah T., Vachon-Presseau E., Berger S., Baria A., Griffith J.W., Baliki M.N., Schnitzer T.J., Apkarian A.V.

Pain and Therapy （Pain and Therapy） 10 （ 2 ） 1375 - 1400 2021年12月

査読有り, ISSN 21938237

Background: Preventing transition to chronic back pain (CBP) is a long-sought strategy that could rescue patients from prolonged suffering. Recent rodent and human brain imaging studies suggest involvement of sexually dimorphic, dopaminergic-motivational, mesolimbic circuits in the transition to chronic pain (tCBP), and hint that the combination of carbidopa/levodopa and naproxen (LDP + NPX) may block tCBP. Here we evaluated, in people with recent-onset back pain, whether a 3-month treatment with LDP + NPX is safe, blocks tCBP, and whether its efficacy is sex-dependent. Methods: A total of 72 participants were enrolled and stratified by risk for tCBP using brain-imaging biomarkers. Low-risk participants entered a no-treatment arm. Others were randomized to placebo + naproxen or LDP + NPX for 3 months. Results: Both treatments resulted in more than 50% pain relief for approximately 75% of participants. A strong sex by treatment interaction was observed for daily pain intensity (phone NRS, P = 0.007), replicated on 4-week average pain (Pain/4w, P = 0.00001), and in intent-to-treat analysis (Pain/4w, P = 0.000004). Nucleus accumbens functional connectivity with medial prefrontal cortex, a predefined objective biomarker, showed sex dependence at baseline (P = 0.03) and sex-by-treatment interaction effect 3 months after treatment cessation (P = 0.031). Treatment modified the psychological profile of participants, and disrupted brain modeling-based predicted back pain intensity trajectories. Forty participants were queried 3.3 years from trial start; back pain ratings were similar between end of treatment and at 3.3 years (P = 0.62), indicating persistence of relief for this duration. Conclusions: These results provide the first evidence for preventing transition to chronic back pain using sex-specific pharmacotherapy. These provocative observations require confirmation in a larger study. ClinicalTrials.gov identifier: NCT01951105.

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脊椎由来疼痛の保存的治療における疼痛関連アウトカムに影響する因子の検討

本田あやか, 星野麗子, 篠原佑太, 石川愛子, 田中智里, 高岡早紀, 辻収彦, 西村大輔, 若泉謙太, 森崎浩, 小杉志都子

日本ペインクリニック学会誌（(一社)日本ペインクリニック学会） 28 （ 9 ） 183 - 189 2021年09月

査読有り, ISSN 1340-4903

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)

Psychosocial, Functional, and Emotional Correlates of Long-Term Opioid Use in Patients with Chronic Back Pain: A Cross-Sectional Case–Control Study

Wakaizumi K., Vigotsky A.D., Jabakhanji R., Abdallah M., Barroso J., Schnitzer T.J., Apkarian A.V., Baliki M.N.

Pain and Therapy （Pain and Therapy） 10 （ 1 ） 691 - 709 2021年06月

査読有り, ISSN 21938237

Introduction: The opiate epidemic has severe medical and social consequences. Opioids are commonly prescribed in patients with chronic pain, and are a main contributor to the opiate epidemic. The adverse effects of long-term opioid usage have been studied primarily in dependence/addiction disorders, but not in chronic pain. Here, we examine the added iatrogenic effects, psychology, and brain morphology of long-term opioid use in matched patients with chronic pain with and without opioid use (case–controlled design). Methods: We compared psychosocial, functional, and psychological measures between patients with chronic back pain (CBP) who were managing their pain with or without opioids, thereby controlling for the effect of pain on these outcomes. In addition, we investigated brain morphological differences associated with long-term opioid usage. We recruited 58 patients with CBP, 29 of them on long-term opioids and 29 who did not use opioids, and who were matched in terms of age, sex, pain intensity, and pain duration. Questionnaires were used to assess pain quality, pain psychology, negative and positive emotions, physical, cognitive, sensory, and motor functions, quality of life, and personality traits. Results: Patients with CBP on opioids displayed more negative emotion, poorer physical function, and more pain interference (p < 0.001), whereas there were no statistical differences in cognitive and motor functions and personality traits. Voxel-based morphometry using structural brain imaging data identified decreased gray matter density of the dorsal paracingulate cortex (family-wise error-corrected p < 0.05) in patients with opioids, which was associated with negative emotion (p = 0.03). Finally, a volumetric analysis of hippocampal subfields identified lower volume of the left presubiculum in patients on opioids (p < 0.001). Conclusion: Long-term opioid use in chronic pain is associated with adverse negative emotion and disabilities, as well as decreased gray matter volumes of specific brain regions.

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【頭痛・めまい・しびれ・疼痛-慢性化のメカニズムと治療】しびれ・疼痛しびれ・疼痛の一般的病態と慢性化のメカニズム大脳の変化

若泉謙太

内科（(株)南江堂） 127 （ 6 ） 1287 - 1292 2021年06月

筆頭著者, 最終著者, 責任著者, ISSN 0022-1961

＜文献概要＞▼国際疾病分類に慢性痛の項目が新設され,原因の特定できない慢性痛に対して「一次性慢性痛」という診断ができるようになった.▼中枢感作の病態を示唆する"nociplastic pain"という用語もつくられた.このような動きの背景には,脳神経の可塑的な変化が痛みの慢性化や重症化に関与することを示す研究成果がある.▼脳画像研究の発展に伴って慢性痛患者ではペイン・マトリックスやデフォルト・モード・ネットワークとよばれる脳部位や神経ネットワークにさまざまな変化が起こっていることがわかってきた.▼脳内報酬系ネットワークは痛みの慢性化の素因となっている可能性が指摘されている.▼慢性痛に対しては,このような大脳の変化を念頭に置いた治療的介入が必要であると考えられる.

【高齢者の疼痛管理を考える】学際的痛み医療と脳機能の改善

若泉謙太

ペインクリニック（真興交易(株)医書出版部） 42 （ 6 ） 722 - 730 2021年06月

筆頭著者, 最終著者, 責任著者, ISSN 0388-4171

著者の所属していた施設(米国シカゴ)で行われていた学際的痛み医療(ペイン・マネジメント・プログラム)について概説する。このプログラムで参加者は、マインドフルネスを含めた様々なリラクゼーション法や運動療法、認知の修正法などを学び、自分の痛みをマネジメントするスキルを獲得する。プログラムの前後を比較すると、参加者は痛みの改善だけでなく、情動面の改善やコーピング・スキルの獲得といった効果を得ることができる。また、脳画像解析において有意な変化も検出でき、脳機能の改善も示唆される。(著者抄録)

Association of work performance and interoceptive awareness of 'body trusting' in an occupational setting: A cross-sectional study

Tanaka C., Wakaizumi K., Kosugi S., Tanaka S., Matsudaira K., Morisaki H., Mimura M., Fujisawa D.

BMJ Open （BMJ Open） 11 （ 5 ） e044303 2021年05月

査読有り

Objectives Work performance has been known to be influenced by both psychological stress (mind) and physical conditions (body). The aim of this study was to investigate the association between work performance and 'body trusting', which is a dimension of interoceptive awareness representing mind-body interactions. Methods A cross-sectional study was conducted among a sample of workers in an industrial manufacturing company in Japan. Participants were assessed with a self-reported questionnaire including evaluations of work performance, body trusting, psychological distress, pain persistence, workplace and home stressors, and workaholism. Participants' sociodemographic, health and lifestyle characteristics were collected from their annual health check data. The association between work performance and body trusting was examined using multivariable regression analyses in the overall sample and in a subsample of people with pain. Results A total of 349 workers participated in the study. A significant association between work performance and body trusting was observed, with higher body trusting representing higher work performance. The association was significant after controlling for psychological distress, workplace and home stress, workaholism and participants' characteristics (p<0.001). Compared with people without pain (n=126, 36.1%), people with pain (n=223, 63.9%) showed less body trusting, which was associated with decreased work performance after controlling for pain-related variables (p<0.001). Conclusions Workers with higher body trusting showed higher work performance, even after controlling for various influencing factors. Body trusting may be an important target to promote work performance and to prevent loss of performance induced by health problems.

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Antenatal pain, intimate partner violence, and maternal bonding disorder: data from the Japan Environment and Children's Study

Yamada K., Kimura T., Cui M., Kubota Y., Tanaka E., Wakaizumi K., Ikehara S., Kimura T., Iso H.

Pain （Pain） 162 （ 3 ） 749 - 759 2021年03月

査読有り

ABSTRACT: This prospective study examined (1) whether antenatal pain is associated with postnatal maternal bonding disorder (MBD) through postnatal depression and (2) whether intimate partner violence (IPV) has a moderating effect on the association between antenatal pain and postnatal MBD. We analyzed 77,326 pregnancies of women who completed self-report questionnaires including the SF-8 bodily pain item, the Edinburgh Postnatal Depression Scale, the Mother-to-Infant Bonding Scale, and an assessment of IPV. We conducted a mediation analysis to assess whether postnatal depression mediated the association between antenatal pain and MBD 1 year after delivery. A moderated mediation model was used to examine the conditional effect of IPV during pregnancy on the association between antenatal pain and postnatal MBD, operating through postnatal depression. All analyses were adjusted for demographic factors, socioeconomic factors, perinatal and infant factors, medical history, and psychological status. Of the 77,326 pregnancies, 5420 (7.0%) were characterized by persistent moderate-to-severe pain. The total effect of antenatal pain on MBD was significant (standardized path coefficient = 0.06, 95% confidence interval, 0.05-0.06) and postnatal depression dominantly mediated the association between antenatal pain and postnatal MBD (70.8% mediation). Contrary to our hypothesis, IPV during pregnancy did not moderate the association between antenatal pain and postnatal MBD. However, IPV during pregnancy did have independent negative effects on both postnatal depression and MBD. Our findings suggest that antenatal pain and postnatal depression should be assessed and treated with consideration of the presence of IPV during pregnancy to better monitor and prevent the development of MBD.

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Reorganization of functional brain network architecture in chronic osteoarthritis pain

Barroso J., Wakaizumi K., Reis A.M., Baliki M., Schnitzer T.J., Galhardo V., Apkarian A.V.

Human Brain Mapping （Human Brain Mapping） 42 （ 4 ） 1206 - 1222 2021年03月

査読有り, ISSN 10659471

Osteoarthritis (OA) manifests with chronic pain, motor impairment, and proprioceptive changes. However, the role of the brain in the disease is largely unknown. Here, we studied brain networks using the mathematical properties of graphs in a large sample of knee and hip OA (KOA, n = 91; HOA, n = 23) patients. We used a robust validation strategy by subdividing the KOA data into discovery and testing groups and tested the generalizability of our findings in HOA. Despite brain global topological properties being conserved in OA, we show there is a network wide pattern of reorganization that can be captured at the subject-level by a single measure, the hub disruption index. We localized reorganization patterns and uncovered a shift in the hierarchy of network hubs in OA: primary sensory and motor regions and parahippocampal gyrus behave as hubs and insular cortex loses its central placement. At an intermediate level of network structure, frontoparietal and cingulo-opercular modules showed preferential reorganization. We examined the association between network properties and clinical correlates: global disruption indices and isolated degree properties did not reflect clinical parameters; however, by modeling whole brain nodal degree properties, we identified a distributed set of regions that reliably predicted pain intensity in KOA and generalized to hip OA. Together, our findings reveal that while conserving global topological properties, brain network architecture reorganizes in OA, at both global and local scale. Network connectivity related to OA pain intensity is dissociated from the major hub disruptions, challenging the extent of dependence of OA pain on nociceptive signaling.

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言語的妥当性を担保した日本語版Injustice Experience Questionnaire-Short Formの作成

山田恵子, 若泉謙太, 壬生彰, 向後響, 井関雅子, 西上智彦

ペインクリニック（真興交易(株)医書出版部） 42 （ 2 ） 239 - 244 2021年02月

ISSN 0388-4171

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)

Sitting for long periods is associated with impaired work performance during the COVID-19 pandemic

Wakaizumi K., Yamada K., Shimazu A., Tabuchi T.

Journal of Occupational Health （Journal of Occupational Health） 63 （ 1 ） e12258 2021年01月

筆頭著者, 責任著者, ISSN 13419145

Objectives: The unprecedented coronavirus disease 2019 (COVID-19) pandemic and the corresponding government state of emergency have dramatically changed our workstyle, particularly through implementing teleworking and social distancing. We investigated the degree to which people's work performance is affected and the association between sedentary behavior under the state of emergency and worsened work performance during the COVID-19 pandemic, as previous studies have suggested that sedentary behavior decreases work performance. Methods: We used data from the Japan “COVID-19 and Society” Internet Survey (JACSIS) study, a cross-sectional, web-based, self-reported questionnaire survey. The main outcome was change in work performance after the COVID-19 pandemic compared with that before the pandemic. We analyzed the association between the change in work performance and sitting duration under the state of emergency, adjusted for work-related stress, participants’ demographics, socio-economic status, health-related characteristics, and personality. Results: The change of work environment from the pandemic decreased work performance in 15% of workers, which was 3.6 times greater than the number of workers reporting increased performance in 14 648 workers (6134 women and 8514 men). Although telework both improved and worsened performance (odds ratio [OR], 95% confidence interval [CI] = 2.0, 1.6-2.5 and 1.7, 1.5-1.9, respectively), sitting for long periods after the state of emergency was significantly associated only with worsened performance (OR, 95% CI = 1.8, 1.5-2.2) in a dose–response manner. Conclusion: Sitting duration is likely a risk barometer of worsened work performance under uncertain working situations, such as the COVID-19 pandemic.

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Momentary pain assessments reveal benefits of endoscopic discectomy: a prospective cohort study

Wakaizumi K., Wu B., Huang S., Fan L., Shen B., Wu B., Zhang J., Baliki M.N., Apkarian A.V., Huang L.

Pain Reports （Pain Reports） 6 （ 1 ） e906 2021年

筆頭著者, 査読有り

Introduction: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.

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【運動器の痛み:どこから来るのか?どこへ行くのか?】(Part1)運動器の痛みどこから来るのか? 慢性腰痛の病態

松平浩, 吉本隆彦, 若泉謙太, 唐司寿一, 笠原諭

Bone Joint Nerve （(株)アークメディア） 10 （ 4 ） 561 - 568 2020年10月

ISSN 2186-1110

慢性疼痛患者分類として質問票スコアにクラスター分析を用いた手法と、国際疾病分類第11版(ICD-11)に基づく分類の関連

河合愛子, 山田恵子, 濱岡早枝子, 千葉聡子, 若泉謙太, 山口敬介, 井関雅子

PAIN RESEARCH （(一社)日本疼痛学会） 35 （ 3 ） 141 - 153 2020年09月

査読有り, ISSN 0915-8588

クラスター分析による慢性疼痛患者分類と国際疾病分類第11版(ICD-11)の慢性疼痛分類を用いた患者分類の関連を分析した。初診時点で痛みの持続期間が3ヵ月以上の慢性疼痛患者229名を対象とした。Two-Stepクラスター分析によって、最適クラスター数は3個であると判定された。ICD-11慢性疼痛分類の大分類ごとの各クラスターが占める割合について、全体のクラスター分布に有意な差があったが、ICD-11慢性疼痛分類の大分類ごとの個別クラスターの割合に統計的有意差はなかった。慢性筋骨格系痛全体を占める重症クラスターの割合と比較して、慢性内臓痛全体を占める重症クラスターの割合が高かった。それ以外の疾患分類については、各疾患分類全体を占める重症クラスターの割合は17.6%から45.5%であり、慢性筋骨格系痛全体を占める重症クラスターの割合と比較して高い傾向であった。クラスター分類は一部のICD-11慢性疼痛分類との関連で臨床的経験やガイドラインの内容と一致する結果であった。

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Pain medications during pregnancy: data from the Japan environment and children’s study

Yamada K., Kimura T., Ikehara S., Cui M., Kubota Y., Wakaizumi K., Takeda T., Iso H.

Journal of Anesthesia （Journal of Anesthesia） 34 （ 2 ） 202 - 210 2020年04月

査読有り, ISSN 09138668

Purpose: Analgesic medication epidemic during pregnancy is an important issue in Western countries. However, no large epidemiological study involving pregnant women with pain and their medication use has been conducted in Japan. This study examined the current situation of medication use for non-cancer pain during the perinatal period in Japan using national cohort data. Methods: We analyzed 94,649 pregnant women who completed a self-report questionnaire investigating bodily pain and an interview-based medication use survey. Medication use before and during pregnancy and new medication administration/discontinuation during pregnancy were compared between women with and without pain during pregnancy using multivariable covariance analysis. Results: Mild pain was reported by 50.4% of pregnant women in the first trimester (survey 1) and 61.8% in the second/third trimester (survey 2). Moderate-to-severe pain was reported by 15.4% of women in survey 1 and 22.4% in survey 2. In survey 1, 6.2% of women used prescribed analgesics and 1.6% used over-the-counter analgesics. In survey 2, prescribed and over the counter analgesics were used by 12.2% and 0.8% of women, respectively. Other pain-related medications were rarely used (< 1.0%). Pregnant women with moderate-to-severe pain showed a lower proportion of discontinuation of analgesics and a higher proportion of new administration of prescription and transdermal analgesics compared with those without pain. Conclusions: Although a large proportion of pregnant women experience pain, medication use for pain during pregnancy is low in Japan compared with Western countries (50–60%). Adequate treatment or support may be necessary for pregnant women experiencing pain in Japan.

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Prediction of postoperative pain and opioid requirement in patients chronically using opioids

Naho Ihara, Shizuko Kosugi, Kenta Wakaizumi, Daisuke Nishimura, Yoko Fukuda, Hiromasa Nagata, Takashige Yamada, Saori Hashiguchi, Hiroshi Morisaki

JOURNAL OF CLINICAL ANESTHESIA （ELSEVIER SCIENCE INC） 60 14 - 15 2020年03月

筆頭著者, 査読有り, ISSN 0952-8180

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【慢性痛へのアプローチ】痛みと脳

若泉謙太

最新精神医学（(株)世論時報社） 25 （ 2 ） 73 - 84 2020年03月

筆頭著者, ISSN 1342-4300

Prognostics for pain in osteoarthritis: Do clinical measures predict pain after total joint replacement?

Barroso J., Wakaizumi K., Reckziegel D., Pinto-Ramos J., Schnitzer T., Galhardo V., Apkarian A.V.

PLoS ONE （PLoS ONE） 15 （ 1 ） e0222370 2020年01月

査読有り, ISSN 1932-6203

A significant proportion of osteoarthritis (OA) patients continue to experience moderate to severe pain after total joint replacement (TJR). Preoperative factors related to pain persistence are mainly studied using individual predictor variables and distinct pain outcomes, thus leading to a lack of consensus regarding the influence of preoperative parameters on post-TJR pain. In this prospective observational study, we evaluated knee and hip OA patients before, 3 and 6 months post-TJR searching for clinical predictors of pain persistence. We assessed multiple measures of quality, mood, affect, health and quality of life, together with radiographic evaluation and performance-based tasks, modeling four distinct pain outcomes. Multivariate regression models and network analysis were applied to pain related biopsychosocial measures and their changes with surgery. A total of 106 patients completed the study. Pre-surgical pain levels were not related to post-surgical residual pain. Although distinct pain scales were associated with different aspects of post-surgical pain, multi-factorial models did not reliably predict post-surgical pain in knee OA (across four distinct pain scales) and did not generalize to hip OA. However, network analysis showed significant changes in biopsychosocial-defined OA personality post-surgery, in both groups. Our results show that although tested clinical and biopsychosocial variables reorganize after TJR in OA, their presurgical values are not predictive of post-surgery pain. Derivation of prognostic markers for pain persistence after TJR will require more comprehensive understanding of underlying mechanisms.

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Psychology, psychiatry, imaging and brain neuroscience section Structural MRI Analysis of chronic pain patients following interdisciplinary treatment shows changes in brain volume and opiate-dependent reorganization of the amygdala and hippocampus

Gagnon C.M., Scholten P., Atchison J., Jabakhanji R., Wakaizumi K., Baliki M.

Pain Medicine (United States) （Pain Medicine (United States)） 21 （ 11 ） 2765 - 2776 2020年

査読有り, ISSN 15262375

Objective. The present study examined pre-to post-treatment changes in volumes for brain structures known to be associated with pain processing (thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and accumbens) following an interdisciplinary pain management program. Design. Twenty-one patients participating in a four-week interdisciplinary pain management program completed the study. The program consisted of individual and group therapies with the following disciplines: Physical therapy, occupational therapy, pain psychology, biofeedback/relaxation training, nursing lectures, and medical management. All patients underwent functional magnetic resonance imaging of the brain before the start and at completion of the program. They also completed standard outcome measures assessing pain, symptoms of central sensitization, disability, mood, coping, pain acceptance, and impressions of change. Results. Our results showed a significant increase in total brain volume, as well as increased volumes in the thalamus, hippocampus, and amygdala. As expected, we also found significant improvements in our standard outcome measures. The majority of patients rated themselves as much or very much improved. The increase in volume in the hippocampus was significantly associated with patient perceptions of change. However, the correlations were in the unexpected direction, such that greater increases in hippocampal volume were associated with perceptions of less improvement. Further exploratory analyses comparing patients by their opioid use status (use vs no use) showed differential program effects on volume increases in the hippocampus and amygdala. Conclusions. These findings show that a four-week interdisciplinary pain management program resulted in changes in the brain, which adds objective findings further demonstrating program efficacy.

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Whole-brain functional network disruption in chronic pain with disk herniation

Huang S., Wakaizumi K., Wu B., Shen B., Wu B., Fan L., Baliki M.N., Zhan G., Apkarian A.V., Huang L.

Pain （Pain） 160 （ 12 ） 2829 - 2840 2019年12月

査読有り, ISSN 03043959

Brain functional network properties are globally disrupted in multiple musculoskeletal chronic pain conditions. Back pain with lumbar disk herniation (LDH) is highly prevalent and a major route for progression to chronic back pain. However, brain functional network properties remain unknown in such patients. Here, we examined resting-state functional magnetic resonance imaging-based functional connectivity networks in chronic back pain patients with clear evidence for LDH (LDH-chronic pain n = 146), in comparison to healthy controls (HCs, n = 165). The study was conducted in China, thus providing the opportunity to also examine the influence of culture on brain functional reorganization with chronic pain. The data were equally subdivided into discovery and validation subgroups (n = 68 LDH-chronic pain and n = 68 HC, for each subgroup), and contrasted to an off-site data set (n = 272, NITRC 1000). Graph disruption indices derived from 3 network topological measurements, degree, clustering coefficient, and efficiency, which respectively represent network hubness, segregation, and integration, were significantly decreased compared with HC, across all predefined link densities, in both discovery and validation groups. However, global mean clustering coefficient and betweenness centrality were decreased in the discovery group and showed trend in the validation group. The relationship between pain and graph disruption indices was limited to males with high education. These results deviate somewhat from recent similar analysis for other musculoskeletal chronic pain conditions, yet we cannot determine whether the differences are due to types of pain or also to cultural differences between patients studied in China and the United States.

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Altered functional connectivity associated with time discounting in chronic pain

Wakaizumi K., Jabakhanji R., Ihara N., Kosugi S., Terasawa Y., Morisaki H., Ogaki M., Baliki M.N.

Scientific Reports （Scientific Reports） 9 （ 1 ） 8154 - 8154 2019年12月

査読有り, ISSN 2045-2322

Chronic pain (CP) is a global problem extensively associated with an unhealthy lifestyle. Time discounting (TD), a tendency to assign less value to future gains than to present gains, is an indicator of the unhealthy behaviors. While, recent neuroimaging studies implied overlapping neuro mechanisms underlying CP and TD, little is known about the specific relationship between CP and TD in behavior or neuroscience. As such, we investigated the association of TD with behavioral measures in CP and resting-state brain functional network in both CP patients and healthy subjects. Behaviorally, TD showed a significant correlation with meaningfulness in healthy subjects, whereas TD in patients only correlated with pain intensity. We identified a specific network including medial and dorsolateral prefrontal cortex (PFC) in default mode network (DMN) associated with TD in healthy subjects that showed significant indirect mediation effect of meaningfulness on TD. In contrast, TD in patients was correlated with functional connectivity between dorsolateral PFC (DLPFC) and temporal lobe that mediated the effect of pain intensity on TD in patients. These results imply that TD is modulated by pain intensity in CP patients, and the brain function associated to TD is shifted from a medial to lateral representation within the frontal regions.

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Smoking is associated with greater pain intensity and pain-related occupational disability in Japanese workers

Yamada K., Wakaizumi K., Kubota Y., Matsudaira K., Shibata M.

Journal of Anesthesia （Journal of Anesthesia） 33 （ 4 ） 523 - 530 2019年08月

査読有り, ISSN 09138668

Purpose: Pain symptom, such as that caused by musculoskeletal disorders, is a major cause of occupational disability. As nicotine intake from smoking increases pain sensitivity, smokers may experience stronger pain and be more likely to experience pain-related disability than non-smokers. The study aim was to examine whether smoking was associated with pain-related occupational disability via pain intensity. Methods: Participants were 1189 workers with pain aged 20–74 years in Japan. Participants completed a self-report questionnaire, which included a question to measure pain-related occupational disability with ordinal-option: (1) without pain-related disability, (2) pain-related presenteeism, and (3) pain-related absenteeism. An ordinal logistic regression model was used to calculate multivariable-adjusted proportional odds ratios (OR) with 95% confidence intervals (CI) for the prevalence of pain-related occupational disability according to smoking status. A multiple mediation analysis was also conducted to assess whether pain sensitivity mediated the association between smoking and pain-related occupational disability. Adjusted variables were demographic variables, socioeconomic status, work-related psychosocial factors, general psychological factors, and pain duration. Results: Current smoking and pain were associated with pain-related occupational disability compared with non-smoking and pain (multivariable OR 1.78; 95% CI 1.26–2.52). Greater pain intensity partially mediated the association of current smoking and pain with pain-related occupational disability. The mediation rate (indirect/total effect) was 25%. Conclusion: Smoking and pain were associated with pain-related occupational disability, partially through greater pain intensity, among Japanese workers.

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Aberrant resting-state functional connectivity of the dorsolateral prefrontal cortex to the anterior insula and its association with fear avoidance belief in chronic neck pain patients

Ihara N., Wakaizumi K., Nishimura D., Kato J., Yamada T., Suzuki T., Hashiguchi S., Terasawa Y., Kosugi S., Morisaki H.

PLoS ONE （PLoS ONE） 14 （ 8 ） e0221023 2019年08月

査読有り, ISSN 1932-6203

Chronic neck pain (CNP), a global health problem, involves a large amount of psychological and socioeconomic burdens. Not only physical causes but also behavioral disorders such as a fear-avoidance belief (FAB) can associate with the chronicity of neck pain. However, functional brain mechanisms underlying CNP and its related behavioral disorders remain unknown. The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to explore how the functional brain networks differed between CNP patients and age- and sex-matched healthy, pain-free controls (HCs). We also investigated whether these possible brain network changes in CNP patients were associated with fear avoidance belief (FAB) and the intensity of pain. We analyzed the resting-state fMRI data of 20 CNP patients and 20 HCs. FAB and the intensity of pain were assessed by Tampa Scale for Kinesiophobia (TSK) and Visual Analog Scale (VAS) of pain. The whole brain analysis showed that CNP patients had significant different functional connectivity (FC) compared with HCs, and the right dorsolateral prefrontal cortex (DLPFC) was a core hub of these altered functional networks. Furthermore, general linear model analyses showed that, in CNP patients, the increased FC between the right DLPFC and the right anterior insular cortex (aIC) significantly associated with increased TSK (p = 0.01, statistical significance after Bonferroni correction: p<0.025), and the FC between the right DLPFC and dorsal posterior cingulate cortex had a trend of inverse association with VAS (p = 0.04). Our findings suggest that aberrant FCs between the right DLPFC and aIC associated with CNP and its related FAB.

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Efficacy and safety of equi-analgesic opioid conversion-based postoperative pain management for patients with chronic opioid use

Ihara N., Kosugi S., Wakaizumi K., Fukuda Y., Nishimura D., Yamada T., Hashiguchi S., Morisaki H.

Japanese Journal of Anesthesiology （Japanese Journal of Anesthesiology） 67 （ 4 ） 350 - 355 2018年04月

ISSN 00214892

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.

オピオイド使用患者の術前オピオイド使用量に応じた術後痛管理の有効性と安全性についての検討前向き観察研究

伊原奈帆, 小杉志都子, 若泉謙太, 福田陽子, 西村大輔, 山田高成, 橋口さおり, 森崎浩

麻酔（克誠堂出版(株)） 67 （ 4 ） 350 - 355 2018年04月

査読有り, ISSN 0021-4892

術前オピオイド使用中の患者の使用量に応じた術後痛管理の有効性と安全性について、前向き観察研究を行った。2014年1月から2016年6月までの期間に、術前からオピオイドを使用していた予定手術患者を対象とし、経口モルヒネ換算60mg・day-1を超えるオピオイド使用患者を高用量群、60mg・day-1以下を低用量群とし、術後モルヒネ使用量、痛み、有害事象について比較した。高用量群(n=9)は低用量群(n=8)より術後モルヒネ使用量が多いにもかかわらず、術後痛が有意に強かった。有害事象の発生率に有意差はなかった。(著者抄録)

Study of chronic pain and its associated risk factors among Japanese industry workers: the Quality of Working Life Influenced by Chronic pain (QWLIC) study.

Keiko Yamada, Kenta Wakaizumi, Kyosuke Fukai, Hiroyasu Iso, Tomotaka Sobue, Masahiko Shibata, Ko Matsudaira

Sangyo eiseigaku zasshi = Journal of occupational health 59 （ 5 ） 125 - 134 2017年10月

査読有り

OBJECTIVES: This study was performed to identify the prevalence, influence, and risk factors associated with chronic pain among Japanese industry workers. METHODS: We investigated 2,544 participants working at a manufacturing company A, a manufacturing company B, and 16 branch shops of a retail chain company C. The participants responded to self-administered questionnaires related to pain. Furthermore, data obtained from the lifestyle interview sheet of an annual health screening examination and those obtained from the questionnaires were merged. We analyzed the association between lifestyles, psychosocial factors, and chronic pain. Age- and sex-adjusted odds ratios were calculated with a 95% confidence interval using the logistic regression model. RESULTS: Of 2,544 participants, 1,914 (1,224 men and 690 women) completed the questionnaire, and the response rate was 75.2%. The prevalence of chronic pain over 3 months was 42.7% and that of chronic pain with work disability was 11.3%. A higher proportion of obesity, smoking habit, insomnia, psychological stress, depressive state, workaholic nature, low social support from supervisors and coworkers, high job demand, low job control, and job dissatisfaction was observed in workers with chronic pain than in workers without pain. CONCLUSIONS: Several risk factors of chronic pain in Japanese industry workers were found. Obesity, smoking habits, sleep disorders, workplace environment, and mental state should be taken into account as risk factors associated with chronic pain issues and general occupational health.

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就労環境における慢性痛の実態調査〜仕事に影響する慢性痛のリスク因子の検討 QWLICスタディ

山田恵子, 若泉謙太, 深井恭佑, 磯博康, 祖父江友孝, 柴田政彦, 松平浩

産業衛生学雑誌（(公社)日本産業衛生学会） 59 （ 5 ） 125 - 134 2017年09月

査読有り, ISSN 1341-0725

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)

情動と行動を軸とした慢性痛治療の新しい方向性慢性痛の運動療法における脳内報酬ドパミン系ネットワークの重要性

若泉謙太

Journal of Musculoskeletal Pain Research （(一社)日本運動器疼痛学会） 9 （ 2 ） 286 - 294 2017年09月

筆頭著者, 査読有り, ISSN 2186-2796

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)

情動と行動を軸とした慢性痛治療の新しい方向性 AMED研究班「慢性痛に対する認知行動療法の普及と効果解明に関する研究」の紹介

柴田政彦, 細越寛樹, 高橋紀代, 安達友紀, 榎本聖香, 山田恵子, 若泉謙太, 松平浩, 北原雅樹, 西江宏行, 堀越勝

Journal of Musculoskeletal Pain Research （(一社)日本運動器疼痛学会） 9 （ 2 ） 267 - 276 2017年09月

査読有り, ISSN 2186-2796

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)

Psychological and endocrine factors and pain after mastectomy

D. Nishimura, S. Kosugi, Y. Onishi, N. Ihara, K. Wakaizumi, H. Nagata, T. Yamada, T. Suzuki, S. Hashiguchi, H. Morisaki

European Journal of Pain (United Kingdom) （Blackwell Publishing Ltd） 21 （ 7 ） 1144 - 1153 2017年08月

査読有り, ISSN 1532-2149

Background: This prospective study was designed to examine the associations of demographic, clinical, psychological and neuroendocrine factors with acute and chronic post-operative pain following partial mastectomy. Methods: Sixty-four female patients scheduled for partial mastectomy were enrolled. Pre-operative anxiety/depression was assessed, using the Hospital Anxiety and Depression Scale (HADS). Pre-operative 24-h urinary cortisol levels were measured 2 days before surgery. Post-operative pain was examined using a visual analog scale (VAS) for acute pain on 0–2 post-operative day (POD), and a short-form McGill Pain Questionnaire for chronic pain at 6 months after surgery. In the last 29 subjects, post-operative 24-h urinary cortisol levels were also measured on 0 POD and were subjected to correlation analysis. Results: Multivariate logistic regression analysis revealed that lower pre-operative cortisol secretion and greater pre-operative anxiety were significantly associated with an increased risk of moderate to severe acute post-operative pain [Odds Ratio (95% Confidence Interval)
0.96 (0.92–0.98), and 1.24 (1.04–1.54)], and that patients with greater pre-operative anxiety and moderate to severe acute pain were more likely to develop chronic post-operative pain [OR (95% CI)
1.63 (1.23–2.40), and 5.07 (1.30–24.6)]. Correlational analysis demonstrated that the post-operative cortisol level was inversely correlated with pre-operative anxiety and the intensity of acute post-operative pain (r = −0.40, p &lt
0.05, and r = −0.50, p &lt
0.01), but not with the intensity of chronic pain. Conclusions: This study confirms that pre-operative anxiety is associated with both acute and chronic post-operative pain after partial mastectomy. It also suggests that lower perioperative cortisol secretion might be associated with greater acute post-operative pain. Significance: Although the associations between psychological stress/stress hormone levels and chronic post-operative pain remain to be determined, pre-operative psychological stress and perioperative cortisol levels are correlated with acute post-operative pain.

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【慢性痛に対する運動療法の効果と応用】特異的神経制御研究が照らし出す運動療法の未来脳内報酬ドパミン系ネットワークの重要性

若泉謙太, 近藤貴茂, 濱田祐輔, 成田年

ペインクリニック（真興交易(株)医書出版部） 38 （ 5 ） 580 - 589 2017年05月

筆頭著者, ISSN 0388-4171

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。薬理遺伝学的手法を用いたこの神経の特異的な抑制により、運動による鎮痛効果(exercise-induced hypoalgesia:EIH)が減弱した。運動療法は、本来の身体機能障害の改善だけでなく、脳報酬系を活性化させることで、痛みを誘発する行動習慣および脳機能障害を含めた総合的な治療手段であると考えられる。報酬系活性化の戦略的手法であるコーチングは、運動療法に付与されることでEIHの強化と運動の習慣化を加速させ、臨床における運動療法の新しい方向性になると期待できる。(著者抄録)

Fear-avoidance beliefs are independently associated with the prevalence of chronic pain in Japanese workers

Kenta Wakaizumi, Keiko Yamada, Hiroyuki Oka, Shizuko Kosugi, Hiroshi Morisaki, Masahiko Shibata, Ko Matsudaira

JOURNAL OF ANESTHESIA （SPRINGER JAPAN KK） 31 （ 2 ） 255 - 262 2017年04月

筆頭著者, 査読有り, ISSN 0913-8668

Pain is a global public health problem with implications for both personal and social heath. Fear-avoidance beliefs (FABs) have been demonstrated to negatively impact and prolong pain in many Western countries, but little is known about the association between FABs and chronic pain (CP) in Asian countries, including Japan. We examined the relationship between FABs and CP in Japanese white-collar workers, a growing population with a high prevalence of CP.Questionnaires and company records were used to gather data from 433 Japanese white-collar workers. Data were related to experience of pain, participant sociodemographic/health/lifestyle characteristics, fear-avoidance beliefs [Tampa Scale for Kinesiophobia (TSK)], work-related psychosocial factors (Brief Job Stress Questionnaire), and depressive illness [Psychological Distress Scale (K6)]. Analysis of covariance and multilevel logistic regression modeling were used to analyze associations between the data while controlling for factors known to influence CP prevalence.Prevalence rate of CP was 11.1% (48 of 433 persons). Adjusted odds ratios for participants with CP significantly increased in participants with high TSK scores, even after adjusting for factors known to influence CP prevalence.We found a significant association between high TSK scores and CP in Japanese white-collar workers when controlling for other known factors that influence CP such as work-related psychosocial characteristics and depressive conditions. This finding suggests that FABs are independently associated with prevalence of CP.

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さまざまな慢性痛患者の安静時fMRI研究

柴田政彦, 寒重之, 大迫正一, 三木健司, 柳澤琢史, 助永憲比古, 恒遠剛示, 新田一仁, 岩下成人, 福井聖, 黒崎弘倫, 中野直樹, 若泉謙太, 上嶋江利, 本山泰士, 高雄由美子, 溝渕知司

PAIN RESEARCH （日本疼痛学会） 31 （ 4 ） 189 - 196 2016年12月

査読有り, ISSN 0915-8588

fMRIは核磁気共鳴現象を利用して脳活動を画像化する非侵襲脳活動計測法の一つで、痛みの研究に応用されてきた。様々な慢性痛患者の脳活動を健常人と比較することによってその脳内機序を探る方法として、近年安静時fMRIが注目されている。線維筋痛症、慢性腰痛、片頭痛、その他の疾患を対象とした安静時fMRIの論文を取り上げ、主な知見をまとめた。

Involvement of mesolimbic dopaminergic network in neuropathic pain relief by treadmill exercise: A study for specific neural control with Gi-DREADD in mice

Kenta Wakaizumi, Takashige Kondo, Yusuke Hamada, Michiko Narita, Rui Kawabe, Hiroki Narita, Moe Watanabe, Shigeki Kato, Emiko Senba, Kazuto Kobayashi, Naoko Kuzumaki, Akihiro Yamanaka, Hiroshi Morisaki, Minoru Narita

MOLECULAR PAIN （SAGE PUBLICATIONS INC） 12 2016年11月

筆頭著者, 査読有り, ISSN 1744-8069

Background: Exercise alleviates pain and it is a central component of treatment strategy for chronic pain in clinical setting. However, little is known about mechanism of this exercise-induced hypoalgesia. The mesolimbic dopaminergic network plays a role in positive emotions to rewards including motivation and pleasure. Pain negatively modulates these emotions, but appropriate exercise is considered to activate the dopaminergic network. We investigated possible involvement of this network as a mechanism of exercise-induced hypoalgesia.Methods: In the present study, we developed a protocol of treadmill exercise, which was able to recover pain threshold under partial sciatic nerve ligation in mice, and investigated involvement of the dopaminergic reward network in exercise-induced hypoalgesia. To temporally suppress a neural activation during exercise, a genetically modified inhibitory G-protein-coupled receptor, hM4Di, was specifically expressed on dopaminergic pathway from the ventral tegmental area to the nucleus accumbens.Results: The chemogenetic-specific neural suppression by Gi-DREADD system dramatically offset the effect of exerciseinduced hypoalgesia in transgenic mice with hM4Di expressed on the ventral tegmental area dopamine neurons. Additionally, anti-exercise-induced hypoalgesia effect was significantly observed under the suppression of neurons projecting out of the ventral tegmental area to the nucleus accumbens as well.Conclusion: Our findings suggest that the dopaminergic pathway from the ventral tegmental area to the nucleus accumbens is involved in the anti-nociception under low-intensity exercise under a neuropathic pain-like state.

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三叉神経節に対する三叉神経痛の治療後に発症した有痛性感覚脱失3症例の治療経験

若泉謙太, 樋田久美子, 米川裕子, 豊川秀樹, 上島賢哉, 安部洋一郎

日本ペインクリニック学会誌（(一社)日本ペインクリニック学会） 21 （ 1 ） 31 - 34 2014年02月

筆頭著者, 査読有り, ISSN 1340-4903

三叉神経節に対する三叉神経痛の治療後に有痛性感覚脱失(anesthesia dolorosa)を発症した3症例を経験したので報告する。症例1は71歳、女性。2年前に他院で三叉神経節バルーン圧迫術を行われた。右三叉神経領域の感覚は消失していたが、右顔面全域でしびれを伴う痛みがあり、視覚的評価尺度(visual analog scale:VAS)で82mmの持続痛であった。アミトリプチリンで痛みは軽減した。症例2は72歳、女性。1年前に他院で微小血管減圧術を行われた。左三叉神経領域の感覚は消失していたが、手術直後から眼窩の異常感覚があり、VASで50mmの持続痛であった。アミトリプチリンで痛みは軽減した。症例3は62歳、女性。1年前に他院でアルコールによる三叉神経節ブロックを行われた。左三叉神経領域の感覚は消失していたが、VASで50mmの持続痛があった。アミトリプチリンは副作用のため効果を判定できなかったがプレガバリンで痛みは軽減した。顔面の有痛性感覚脱失は、三叉神経節に対する三叉神経痛の治療後に低確率で発症する。一般に難治性の痛みであるが、3症例とも痛みを軽減することができた。(著者抄録)

難治性の低血圧、徐脈、低血糖から副腎不全と考え治療した1症例

岩室賢治, 原口靖比古, 若泉謙太, 本保晃, 福山達也, 小山薫, 宮尾秀樹

日本集中治療医学会雑誌（(一社)日本集中治療医学会） 19 （ 1 ） 61 - 64 2012年01月

査読有り, ISSN 1340-7988

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)

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