Published papers

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。

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.

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.

PurposePain 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.MethodsParticipants were 1189 workers with pain aged 20-74years 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.ResultsCurrent 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%.ConclusionSmoking and pain were associated with pain-related occupational disability, partially through greater pain intensity, among Japanese workers.

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.

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.

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.

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.

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)

＜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.

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)

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。

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)

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)

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.

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.

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.