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Objective To evaluate the safety and efficacy of duloxetine treatment for 52 weeks. Design Multicenter, open-label, phase III clinical study. Setting Forty-one medical institutions in Japan. Subjects Japanese patients with chronic low back pain (CLBP). Methods Duloxetine 60 mg once-daily was administered for 52 weeks. Safety was evaluated based on adverse events (AEs), vital signs, laboratory test values, electrocardiogram, Columbia-Suicide Severity Rating Scale, and occurrence of falls. The efficacy outcome measures were the Brief Pain Inventory (BPI; average pain, worst pain, least pain, and pain right now), BPI Interference, Patient's Global Impression of Improvement (PGI-I), Clinical Global Impressions of Severity (CGI-S), Roland-Morris Disability Questionnaire–24 (RDQ-24), 36-Item Short-Form Health Survey (SF-36), and European Quality of Life-5 Dimensions Questionnaire (EQ-5D). Results In total, 151 patients (83 who completed a 14-week placebo-controlled superiority trial and 68 newly registered patients) were enrolled. The incidence rates of AEs and adverse drug reactions (ADRs) were 86.1% and 50.3%, respectively. ADRs with an incidence of ≥5% were somnolence, constipation, nausea, and dry mouth. Treatment discontinuation for AEs occurred in 16 patients. A significant reduction in the BPI average pain score (mean ± SD) was observed at all assessment time points from week 2 (−1.02 ± 1.37) to week 50 (−2.26 ± 1.63), compared with baseline. BPI pain severity (worst pain, least pain, and pain right now), BPI Interference, PGI-I, CGI-S, RDQ-24, SF-36, and EQ-5D showed significant improvement. Conclusion Japanese patients with CLBP had significant pain reduction over 52 weeks without new safety concerns. [ABSTRACT FROM AUTHOR]

Most chronic low back pain includes elements of nociceptive pain, neuropathic pain, and nonorganic pain. We conducted screening for nonorganic pain with use of the Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP), which is simple and can be used for multidimensional assessment. Research on pain areas using functional magnetic resonance imaging (fMRI) and positron emission tomography has shown that the dopamine system contributes to the pathology of chronic low back pain. Chronic low back pain patients show decreased activation of the anterior cingulate cortex, prefrontal cortex, and nucleus accumbens. Given that both the anterior cingulate cortex and prefrontal cortex belong to the descending inhibitory system, and that the nucleus accumbens, which is involved in the dopamine system, releases μ-opioids that act to relieve pain, decreased activation in these three brain regions may be related to decreased function of the descending inhibitory system. A pathological condition that can be explained at the molecular biological level clearly exists between chronic low back pain and psychosocial factors, and investigations of a pathological condition of chronic low back pain including brain function are needed. [ABSTRACT FROM AUTHOR]

Background: In 2007, the Japanese orthopaedic association back pain evaluation questionnaire (JOABPEQ) was established to overcome the limitations of the original JOA scoring system developed in 1986. Although this new self-administered questionnaire is a more accurate outcome measure for evaluating patients with low back pain, physicians were unable to as certain the exact status of a patient at a single time point because of a lack of reference values. This study aimed to establish the reference values of JOABPEQ in different age and gender groups using data obtained from healthy volunteers. Methods: This study was conducted in 21 university hospitals and affiliated hospitals from October 2012 to July 2013. The JOABPEQ includes 25 questions that yield five domains to evaluate individuals with low back pain from five different perspectives. A total of 1,456 healthy volunteers (719 men, 737 women; age range, 20-89 years) answered the questionnaire. The differences in scores according to age and gender were examined by non-parametric tests. Results: The JOABPEQ scores significantly decreased with age in the domains of lumbar spine dysfunction, gait disturbance, and social life dysfunction. In these three domains, the median scores approached the 100 possible points in individuals aged 20-70 for both genders. However, the median scores for lumbar spine dysfunction and social life dysfunction decreased to 83.0 and 65.0-78.0 points, respectively, in individuals in their 80 s and 70-80 s, respectively; and the scores for gait disturbance decreased to 93.0 and 71.0 points for males and females in their 80 s. Overall, the median scores for pain-related and psychological disorders were 100 and 60.0-72.0 points, respectively. Conclusion: The reference values for JOABPEQ according to age and gender were established herein. Patients with low back pain should be evaluated with this new self-administered questionnaire taking these reference values into account. [ABSTRACT FROM AUTHOR]

Background: An outcome measure to evaluate the neurological function of patients with cervical myelopathy was proposed by the Japanese Orthopaedic Association (JOA score) and has been widely used in Japan. However, the JOA score does not include patients' satisfaction, disability, handicaps, or general health, which can be affected by cervical myelopathy. In 2007, a new outcome measure, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), which is a self-administered questionnaire, was developed. However, the influence of age and gender on the scores has not been fully examined. The purpose of this study was to establish the standard value of the JOACMEQ by age using healthy volunteers. Methods: This study was conducted in 23 university hospitals and their affiliated hospitals from September to December 2011. The questionnaire included 24 questions for evaluation of physical function of the cervical spine and spinal cord. A total of 1,629 healthy volunteers were recruited for the study. The ages ranged from 20 to 89 years old. Results: The volunteers comprised 798 men and 831 women. In the elderly healthy volunteers, the JOACMEQ scores decreased with age. In general, the scores for cervical spine function and upper/lower extremity function were retained up to the 60s, then decreased in the 70s and 80s. The scores for quality of life were retained up to the 70s; however, the score for bladder function was retained up to the 40s, then declined with age from the 50s to 80s. Conclusion: The standard values of the JOACMEQ by age were established. Differences in the scores were found among different generations. Patients with cervical myelopathy should be evaluated with this new self-administered questionnaire taking into account the standard values according to different ages. [ABSTRACT FROM AUTHOR]

Background data: There is a considerable difference in pain perception among individuals. In patients with chronic pain, recent studies using fMRI, PET and SPECT have shown that functional changes mainly occurred in the anterior cingulate cortex (ACC), prefrontal cortex (PFC) and thalamus. Brain magnetic resonance spectroscopy (MRS) can evaluate brain chemistry by measuring metabolites such as N-acetyl aspartate (NAA). The purpose of this study was to analyze whether brain MRS could assess pain due to lumbar spine diseases. Methods: NAA levels were determined relative to the concentration of creatine/phosphocreatine complex (Cr) and choline (Cho), which is commonly used as an internal standard. The NAA/Cr and NAA/Cho ratios in the ACC, PFC and thalamus were compared between six patients with unilateral pain (left side) and six control patients without pain. Results: In the right thalamus (contralateral side to symptom), the NAA/Cr in the patients with pain was statistically significantly lower compared with the control patients ( p < 0.05). Also, in the right thalamus, the NAA/Cho in pain patients was significantly lower compared with controls ( p < 0.01). When considering just the right thalamus, there were statistically significant correlations between the numerical rating scale for pain (NRS) and NAA values. Conclusions: Lumbar pain can be assessed indirectly by analyzing the decrease in NAA concentration in the thalamus. [ABSTRACT FROM AUTHOR]

Blood vessel clots are found around the nerve root in patients with lumbar disc herniation. Thrombosis formation in the experimental application of nucleus pulposus to the nerve root has been shown in histological studies. In addition, reduction of blood flow and nerve conduction velocity are induced by the application of nucleus pulposus, which mimics lumbar disc herniation. In patients with lumbar disc herniation, nerve root block, which is thought to increase nerve blood flow, improves radiculopathy. 5-HT2A receptor antagonists are used in chronic arterial occlusive diseases to improve blood flow and have been reported to work as well as nonsteroidal anti-inflammatory drugs in improving radiculopathy due to lumbar disc herniation in clinical studies. This study investigated the effects of a 5-HT2A receptor antagonist on blood vessel diameter and blood flow in a canine experimental model of lumbar disc herniation. A total of 13 dogs were used. The animals were divided into three experimental groups and surgery was performed 1 week before measurements. In the nucleus pulposus group (NP; n = 5), the nucleus pulposus was applied to the nerve roots from the ventral side. In the sham group ( n = 5), nucleus pulposus was not applied. In the naïve group ( n = 3), the animals did not undergo surgery. Measurements of vessel diameter and blood flow were done before and after administration of saline and drugs. The diameters and blood flow volume of the observed blood vessels were measured on video-recordings every 10 min for 65 min. In all groups, vessel diameter and blood flow did not change before or after administration of saline. In the NP and sham groups, vessel diameter and blood flow increased significantly after administration of 5-HTRA compared with the naïve group. 5-HTRA improved blood vessel diameter and blood flow in the nerve roots inflamed by the application of nucleus pulposus but not in the intact nerve roots. 5-HTRA might be a potential agent to improve blood flow in the nerve roots of patients with lumbar disc herniation. [ABSTRACT FROM AUTHOR]

Reduction of blood flow in compressed nerve roots is considered as one important mechanism of induction of neurogenic intermittent claudication in lumbar spinal canal stenosis. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, and is increased in expression in hypoxic conditions. The objective of this study was to examine if cauda equina compression affects motor function and induces expression of VEGF and angiogenesis. The cauda equina was compressed by placing a piece of silicone rubber into the L5 epidural space. Walking duration was examined by rota-rod testing. The compressed parts of the cauda equina and L5 dorsal root ganglion (DRG) were removed at 3, 7, 14, or 28 days after surgery, and processed for immunohistochemistry for VEGF and Factor VIII (marker for vascular endothelial cells). Numbers of VEGF-immunoreactive (IR) cells and vascular density were examined. Walking duration was decreased after induction of cauda equina compression. The number of VEGF-IR cells in the cauda equina and DRG was significantly increased at 3, 14, and 28 days after cauda equina compression, compared with sham-operated rats (P < 0.05). Vascular density in the cauda equina was not increased at any of the time points examined. Cauda equina compression decreased walking duration, and induced VEGF expression in nerve roots and DRG. [ABSTRACT FROM AUTHOR]

The article presents a medical research on neurofilament-immunoreactive afferents in the substantia gelatinosa induced by compression of the dorsal root ganglion (DRG). Allodynia was demonstrated by a decrease of mechanical withdrawal threshold and c-Fos expression in the superficial dorsal horn induced by non-noxious stimulation. It revealed that the changes may be related to alloydynia induced by DRG compression.

Background: There is no validated gold-standard diagnostic support tool for LSS, and therefore an accurate diagnosis depends on clinical assessment. Assessment of the diagnostic value of the history of the patient requires an evaluation of the differences and overlap of symptoms of the radicular and cauda equina types; however, no tool is available for evaluation of the LSS category. We attempted to develop a self-administered, self-reported history questionnaire as a diagnostic support tool for LSS using a clinical epidemiological approach. The aim of the present study was to use this tool to assess the diagnostic value of the history of the patient for categorization of LSS. Methods: The initial derivation study included 137 patients with LSS and 97 with lumbar disc herniation who successfully recovered following surgical treatment. The LSS patients were categorized into radicular and cauda equina types based on history, physical examinations, and MRI. Predictive factors for overlapping symptoms between the two types and for cauda equina symptoms in LSS were derived by univariate analysis. A self-administered, self-reported history questionnaire (SSHQ) was developed based on these findings. A prospective derivation study was then performed in a series of 115 patients with LSS who completed the SSHQ before surgery. All these patients recovered following surgical treatment. The sensitivity of the SSHQ was calculated and clinical prediction rules for LSS were developed. A validation study was subsequently performed on 250 outpatients who complained of lower back pain with or without leg symptoms. The sensitivity and specificity of the SSHQ were calculated, and the test-retest reliability over two weeks was investigated in 217 patients whose symptoms remained unchanged. Results: The key predictive factors for overlapping symptoms between the two categories of LSS were age > 50, lower-extremity pain or numbness, increased pain when walking, increased pain when standing, and relief of symptoms on bending forward (odds ratio ≥ 2, p < 0.05). The key predictive factors for cauda equina type symptoms were numbness around the buttocks, walking almost causes urination, a burning sensation around the buttocks, numbness in the soles of both feet, numbness in both legs, and numbness without pain (odds ratio ≥ 2, p < 0.05). The sensitivity and specificity of the SSHQ were 84% and 78%, respectively, in the validation data set. The area under the receiver operating characteristic curve was 0.797 in the derivation set and 0.782 in the validation data set. In the test-retest analysis, the intraclass correlation coefficient for the first and second tests was 85%. Conclusion: A new self-administered, self-reported history questionnaire was developed successfully as a diagnostic support tool for LSS. [ABSTRACT FROM AUTHOR]

Few epidemiological studies have evaluated associations between lumbar facet joint (LFJ) osteoarthritis (OA) and comorbidities. This study aimed to investigate the prevalence of LFJ OA in a Japanese community population and associations between LFJ OA and underlying diseases, including lower extremity OA. This epidemiological cross-sectional study evaluated LFJ OA in 225 Japanese community residents (81 males, 144 females; median age, 66 years) using magnetic resonance imaging (MRI). LFJ OA from L1–L2 to L5–S1 was evaluated using a 4-grade classification. Associations between LFJ OA and comorbidities were examined using multiple logistic regression analyses adjusting for age, sex, and body mass index. Prevalences of LFJ OA were 28.6% at L1–L2, 36.4% at L2–L3, 48.0% at L3–L4, 57.3% at L4–L5, and 44.2% at L5–S1. Males were significantly more likely to have LFJ OA at several spinal levels (L1–L2 45.7% vs 18.9%, p < 0.001; L2–L3 46.9% vs 30.6%, p < 0.05; L4–L5 67.9% vs 51.4%, p < 0.05). LFJ OA was present in 50.0% of residents <50 years old, 68.4% at 50–59 years old, 86.3% at 60–69 years old, and 85.1% at ≥70 years old. Multiple logistic regression analysis showed no associations between LFJ OA and comorbidities. The prevalence of LFJ OA as evaluated by MRI was >85% at ≥60 years old and highest at the L4–L5 spinal level. Males were significantly more likely to have LFJ OA at several spinal levels. Comorbidities were not associated with LFJ OA. [ABSTRACT FROM AUTHOR]

Low back pain can affect musculoskeletal problems of the upper limb in adolescent overhead athletes. However, few epidemiological studies have examined this causal relationship. This prospective cohort study aimed to investigate the relationship between baseline low back pain experience and the occurrence of future shoulder and elbow pain among high school baseball players. Participants comprised 383 high school baseball players from 43 high school baseball teams who had undergone baseline medical evaluations (a self-completed questionnaire and physical examination). The occurrence of shoulder and elbow pain during a 1-year follow-up and associations with baseline low back pain (positive subjective symptom during the last year at baseline) adjusted for flexibility of the scapulo-thoracic region, shoulder, and lower extremities, such as straight-leg raise angle (hamstring tightness), Thomas test (iliopsoas tightness), heel-buttock-distance (quadriceps tightness) and passive range of motion of the hip were investigated using multivariable analysis. A total of 307 players (80.2%) participated in the 1-year follow-up survey, with shoulder and elbow pain reported in 75 players (24.4%) and 119 players (38.8%), respectively, during follow-up. After adjusting for factors associated with shoulder pain using logistic regression modeling, significant associations between LBP experienced during the last year at baseline (odds ratio, 2.18; 95% confidence interval, 1.23–3.87; P = 0.0078) and new-onset of shoulder pain were noted. Baseline low back pain impacted future shoulder pain in high school baseball players during the 1-year follow-up. Management of shoulder pain warrants careful attention to low back pain. [ABSTRACT FROM AUTHOR]

Background: Many adolescent athletes experience low back pain; the most common cause is lumbar spondylolysis. Although early identification of lumbar spondylolysis in adolescent athletes is critical, few studies have focused on identifying the early stages of spondylolysis in baseball players. This study aimed to investigate the clinical characteristics of early-stage spondylolysis in male adolescent baseball players.Methods: The participants comprised male junior and high school baseball players. Before magnetic resonance imaging, we recorded their demographic data, low back pain characteristics, and physical findings (lumbar flexion, extension, Kemp's test and the provocative tenderness of a spinous process). After the imaging evaluation, the association among low back pain characteristics, physical findings and the final diagnosis (early-stage spondylolysis or not) were investigated using univariate and multivariable analyses.Results: A total of 171 players were included in this study. Univariate analyses indicated that the characteristics associated with early-stage spondylolysis were longer duration of low back pain (P = 0.0085), low back pain-related interference while running (P = 0.0022), low back pain starting with laterality (P = 0.0001), lumbar extension (P = 0.022), positive Kemp's test (P = 0.020), and the tenderness of a spinous process (P = 0.0003). After adjusting for confounding factors (age and position), we found that early-stage spondylolysis was significantly associated with low back pain duration ≥4 weeks (odds ratio 3.13, 95% confidence interval 1.42-6.92; P = 0.0048), low back pain-related interference while running (odds ratio 2.89, 95% confidence interval 1.30-6.46; P = 0.0094), low back pain starting with laterality (odds ratio 2.78, 95% confidence interval 1.24-6.27; P = 0.0133), and the tenderness of a spinous process (odds ratio 3.00, 95% confidence interval 1.36-6.57; P = 0.0062).Conclusions: Male adolescent baseball players with early-stage spondylolysis might have low back pain duration of more than four weeks, low back pain-related interference while running, and a history of low back pain starting with laterality. The tenderness of a spinous process might be helpful in the diagnosis of early-stage spondylolysis in male adolescent baseball players. [ABSTRACT FROM AUTHOR]

Introduction: Psychological and social factors are involved in the disability and chronicity of pain. Our study aim was to investigate whether social defeat stress (SDS) as a psychophysical stress affected mechanical withdrawal thresholds in the lumbar disk herniation (LDH) rat model. Changes in microglia and astrocytes, which play important roles in neuropathic pain states, were also investigated.Materials and Methods: For the LDH model, nucleus pulposus (NP) was applied to the L5 dorsal root ganglion (DRG) in adult female Sprague-Dawley rats. SDS was performed 15 min daily for 8 days. Mechanical withdrawal thresholds were measured, and immunoreactive cells of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 (Iba-1), which were used as markers of microglia, satellite glial cells, and astrocytes, were assessed in the DRG, spinal cord (SC), and ventrolateral periaqueductal gray matter (VLPAG).Results: Mechanical withdrawal thresholds decreased in the NP group for 21 days and for 35 days in the NP + SDS group. Expression of GFAP and Iba-1 in the DRG and SC increased up to day 21 in the NP and NP + SDS groups. In the sham + SDS and NP + SDS groups, expression of GFAP in the VLPAG decreased until day 35.Conclusion: SDS prolongs mechanical allodynia induced by NP. Changes of GFAP expression in the VLPAG were associated with mechanical allodynia of the NP + SDS group during the late phase. These results suggest that psychological chronic stress might delay recovery from mechanical allodynia induced by the LDH model. [ABSTRACT FROM AUTHOR]

Introduction: Various drugs are used to treat patients with neuropathic pain; however, optimal treatment using acetaminophen (A) and/or tramadol (T) remains unclear. The evidence supporting the drug choice and the timing of administration is insufficient. Therefore, the objective of the present study was to investigate the effect of T and/or A on pain-related behavior in a nucleus pulposus (NP) rat model.Materials and Methods: Sprague-Dawley rats (n = 180) were divided into NP-A (52 mg/kg), NP-T (6 mg/kg), NP-AT (combined A and T), NP-S (saline), and sham groups (n = 36 per group). The rats received 0.2 mL of treatment solution orally once daily for 7 days after application of NP on the left L5 dorsal root ganglion (DRG). Behavioral testing and immunohistochemistry analysis for some markers' expressions in DRGs and the spinal cord were performed.Results: Pain thresholds in the NP-AT group did not significantly differ from the sham at all time points, while those were significantly lower in the NP-A and in the NP-T groups at D7 and/or D14 (p < 0.05). Tumor necrosis factor-α in the NP-S group was significantly higher at D2 and D7 (p < 0.05). Among the three treatment groups, activating transcriptional factor 3 and growth-associated protein 43 showed a tendency toward an increase at D7-D21.Conclusion: Combined administration of acetaminophen and tramadol maintained in the pain threshold in the rat NP model. These findings suggest that the combination of acetaminophen and tramadol might be a potential therapeutic modality for patients with lumbar disc herniation. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Aim: Dysphagia is a problem typically associated with aging. The aim was to investigate the relationship between dysphagia and motor function using a simple assessment method that can be performed in the community setting, and to promote the early detection and prevention of dysphagia. Methods: Data from the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) were used. Those aged ≥65 years were included. Motor function was assessed using a grip strength test, single limb standing test (SLS), and timed up and go test (TUG). Swallowing function was assessed using the Japanese version of the 10‐item Eating Assessment Tool (EAT‐10). The association between motor function and swallowing function was analyzed. Results: In total, 1732 participants were included. In logistic regression modes in which grip strength, SLS, and TUG results were included separately, the odds ratio for dysphagia increased by 1.08 (P = 0.001) for each 1‐kg decrease in grip strength, and increased by 1.15 (P < 0.001) for each 1‐s increase in TUG time. No association was found for SLS. In the model in which grip strength and TUG were included simultaneously, the odds ratio for dysphagia increased by 1.06 (P = 0.01) in grip strength, and increased by 1.11 (P = 0.009) in TUG time. Conclusion: Our results suggest that skeletal muscle strength and dynamic balance function are associated with dysphagia in community‐dwelling older people. Geriatr Gerontol Int 2023; 23: 603–608. [ABSTRACT FROM AUTHOR]

The Japanese Society for Spine Surgery and Related Research previously developed a diagnostic support tool for lumbar spinal stenosis (LSS-DST). Using the LSS-DST, general physicians can identify potential cases of LSS. However, in the LSS-DST, measurement of the ankle brachial pressure index (ABI) is required to exclude peripheral artery lesions in the lower limbs. We can expect further application of the LSS-DST if we can identify a simpler and easier method than ABI measurement. Therefore, in this large-scale, multicenter, cross-sectional study, we verified whether palpation of the posterior tibial (PT) artery could be used instead of ABI in the LSS-DST. This survey was conducted at 2177 hospitals and included 28,883 participants. The sensitivity and specificity of the original LSS-DST method using the ABI and that of the LSS-DST ver2.0 with PT artery palpation were assessed to screen their ability for diagnosing LSS, using the physicians' final diagnosis based on the patients' history, physical examination and radiographic findings as the gold standard. The sensitivity and specificity [95%CI] of the LSS-DST were 88.2% [87.5, 88.8] and 83.9% [83.4, 84.5], respectively, whereas the sensitivity and specificity of the LSS-DST ver2.0 were 87.7% [87.0, 88.3] and 78.3% [77.7, 78.9], respectively, indicating that LSS-DST ver2.0 is a useful screening tool for LSS with good sensitivity. When the item of ABI in the LSS-DST is replaced by palpation of the PT artery (LSS-DST ver2.0), its sensitivity is maintained as a screening tool for LSS. Level 3. [ABSTRACT FROM AUTHOR]

Purpose: It remains unclear whether musculoskeletal diseases are risk factors for dementia development. This prospective cohort study of community-dwelling residents aimed to clarify the impact of lumbar spinal stenosis (LSS) on dementia development. Methods: We included participants aged ≥ 65 years from the Locomotive Syndrome and Health Outcomes in the Aizu cohort study. LSS was diagnosed using the validated LSS diagnostic support tool. Dementia development between 2008 and 2015 was investigated using official long-term care insurance certification data. We analysed the effects of LSS on dementia development after adjusting for potential confounders, like age, sex, diabetes, depressive symptoms, hip and knee joint osteoarthritis, daily activity, and smoking habit. Results: We included 1220 patients in the final analysis. The incidence of dementia was significantly higher in the LSS group [48 of 444 (10.8%)] than in the control group [34 of 776 (4.4%)]. Multivariable analysis using multiple imputations revealed that the confidence interval for the adjusted odds ratio of LSS for dementia development was 1.87 (95% confidence interval; 1.14–3.07). Conclusion: We clarified that LSS is an independent risk factor for dementia development. Our findings suggest the importance of considering the risk of dementia in the decision-making process for the treatment of LSS. [ABSTRACT FROM AUTHOR]

Introduction: In Japan, conservative therapy for patients with lumbar spinal stenosis (LSS) includes non-steroidal anti-inflammatory drugs (NSAIDs), prostaglandin E1, tramadol, physical/exercise therapy, and nerve blocks. Mirogabalin, a selective oral α2δ ligand, is approved for treating peripheral neuropathic pain, though data regarding visual analog scores (VAS) for pain in patients with LSS are limited. We investigated the efficacy and safety of mirogabalin as an add-on treatment in patients with LSS taking NSAIDs compared with patients taking NSAIDs only. Methods: This multicenter, randomized, open-label study (MiroTAS) was conducted at 32 centers in Japan between June 2020 and October 2021. Patients were randomly assigned to mirogabalin and NSAIDs or NSAIDs alone in a 1:1 ratio. NSAIDs were administered according to their Japanese package inserts; mirogabalin was administered based on renal function [creatinine clearance (CrCL) ≥ 60 mL/min, 5 mg twice daily (BID) in Weeks 1–2, 10 mg BID in Weeks 3–4, and 15 or 10 mg BID after Week 5; CrCL 30 to < 60 mL/min, 2.5 mg BID Weeks 1–2, 5 mg BID Weeks 3–4, and 7.5 or 5 mg BID after Week 5]. The primary endpoint was the change in VAS score for leg pain from baseline to Week 12. Secondary endpoints were quality of life, evaluated using the EuroQol five-dimensional descriptive system (EQ-5D-5L) (at baseline and Week 12) and Patient Global Impression of Change (PGIC) (at Week 12), and safety. Change in VAS score at Week 12 was calculated using a linear mixed model for repeated measures. The safety endpoints were treatment-emergent adverse events (TEAEs) and adverse drug reactions. Results: In total, 220 patients who met the eligibility criteria were enrolled. In the mirogabalin and NSAIDs and NSAIDs groups, mean ages (67.8 vs. 70.9 years), proportions of female patients (54.5% vs. 49.0%), mean body weights (63.9 vs. 62.0 kg), mean CrCL values (81.5 vs. 70.7 mL/min), proportions of patients with CrCL 30 to < 60 mL/min (27.3% vs. 33.7%), mean VAS scores (63.8 vs. 62.8 mm), and proportions of patients with VAS score ≥ 60 (53.6% vs. 52.9%) at enrollment were similar. The median durations of LSS were 9.0 and 11.0 months and the spine pain DETECT questionnaire (SPDQ) scores were 6.8 and 7.8, respectively. The least square (LS) mean change in VAS score from baseline to Week 12 was − 24.1 mm in the mirogabalin and NSAIDs group and − 14.2 mm in the NSAIDs group (both P < 0.0001 vs. baseline). The difference in LS mean was − 9.9 [95% confidence interval (CI), − 18.0, − 1.8] (P = 0.0174). The improvement in EQ-5D-5L score at Week 12 was significantly greater in the mirogabalin and NSAIDs group versus the NSAIDs group [mean difference, 0.0529 (95% CI, 0.0036, 0.1022), P = 0.0357]. At Week 12, the proportions of patients with PGIC scores ≤ 3 and ≤ 2 were higher in the mirogabalin and NSAIDs group vs. the NSAIDs group (76.2% vs. 50.0%, P = 0.0006, and 47.6% vs. 32.4%, P = 0.0523). In the mirogabalin and NSAIDs group, the incidences of TEAEs and adverse drug reactions were 60.9% and 57.3%, respectively, and the most common TEAEs were somnolence (30.0%) and dizziness (25.5%). Conclusions: The addition of mirogabalin to NSAIDs improved VAS, EQ-5D-5L, and PGIC. The main TEAEs were somnolence and dizziness. The addition of mirogabalin to NSAIDs improved peripheral neuropathic pain associated with LSS and raised no new safety concerns. Trial Registration: Japan Registry of Clinical Trials (jRCTs021200007). [ABSTRACT FROM AUTHOR]

Fenofibrate is a fibric acid derivative indicated for use in the treatment of primary hypercholesterolaemia, mixed dyslipidaemia and hypertriglyceridaemia in adults who have not responded to nonpharmacological measures. Its lipid-modifying effects are mediated by activation of peroxisome proliferator-activated receptor-α. Fenofibrate also has nonlipid (i.e. pleiotropic) effects (e.g. it reduces fibrinogen, C-reactive protein and uric acid levels and improves flow-mediated dilatation).Fenofibrate improves lipid levels (in particular triglyceride [TG] and high-density lipoprotein-cholesterol [HDL-C] levels) in patients with primary dyslipidaemia. Its lipid-lowering profile means that fenofibrate is particularly well suited for use in atherogenic dyslipidaemia (characterised by high TG levels, low HDL-C levels and small, dense low-density lipoprotein [LDL] particles), which is commonly seen in patients with the metabolic syndrome and type 2 diabetes mellitus. Indeed, fenofibrate improves the components of atherogenic dyslipidaemia in patients with these conditions, including a shift from small, dense LDL particles to larger, more buoyant LDL particles. Greater improvements in lipid levels are seen when fenofibrate is administered in combination with an HMG-CoA reductase inhibitor (statin) or in combination with ezetimibe, compared with monotherapy with these agents. In the DAIS study, fenofibrate significantly slowed the angiographic progression of focal coronary atherosclerosis in patients with type 2 diabetes. In terms of clinical outcomes, although no significant reduction in the risk of coronary events was seen with fenofibrate in the FIELD trial in patients with type 2 diabetes, treatment was associated with a significantly reduced risk of total cardiovascular disease (CVD) events, primarily through the prevention of non-fatal myocardial infarction and coronary revascularisation. Subgroup analyses revealed significant reductions in total CVD events and coronary heart disease events in patients with no previous CVD, suggesting a potential role for primary prevention with fenofibrate in patients with early type 2 diabetes. Improvements were also seen in microvascular outcomes with fenofibrate in the FIELD trial. Fenofibrate is generally well tolerated, both as monotherapy and when administered in combination with a statin. Combination therapy with fenofibrate plus a statin appears to be associated with a low risk of rhabdomyolysis; no cases of rhabdomyolysis were reported in patients receiving such therapy in the FIELD trial. Thus, fenofibrate is a valuable lipid-lowering agent, particularly in patients with atherogenic dyslipidaemia. [ABSTRACT FROM AUTHOR]

Background: Lumbar spinal stenosis (LSS) is one of the important health problems in an aging society because it can significantly impair quality of life (QOL) and active daily living (ADL). However, the natural history or long-term change of LSS symptoms is still unclear. The purpose of this study was to clarify the 10-year course of lumbar spinal stenosis (LSS) symptoms in community-dwelling residents of more than 1000 people with prospective data collection. Methods: A total of 1149 subjects were analyzed for the time course of LSS symptoms for ten years. LSS symptoms were assessed using a questionnaire specially designed and validated to detect LSS symptoms without image information such as magnetic resonance imaging. Results: The prevalence of positive LSS symptoms was about 16% in the initial survey and 10-year follow-up. Of the subjects who were LSS positive at the initial survey, 40% showed positive LSS symptoms at follow-up and 60% switched to negative LSS symptoms. According to the multivariable logistic regression analysis, severe depression and positive LSS symptoms were extracted as predictors of the presence of LSS symptoms after a 10-year follow-up. Conclusion: The statistical predictor of the presence of LSS symptoms at 10 years was the presence of LSS symptoms at the initial survey; however, 60% of those who were positive for LSS symptoms at the initial survey were not determined to have LSS symptoms at the 10-year follow-up. This was the same result as at the 1-year and 6-year follow-up. [ABSTRACT FROM AUTHOR]

Early diagnosis of degenerative cervical myelopathy (DCM) is desirable, as delayed treatment can cause irreversible spinal cord injury and subsequent activity of daily living (ADL) impairment. We attempted to develop a straightforward and accurate diagnostic tool for DCM by combining the grip and release test (GRT) and grip strength. As a pilot study, we measured the GRT and grip strength of patients with DCM (n = 247) and a control group (n = 721). Receiver operating characteristic analysis was performed using the lower left and right. The Youden index was used to set cutoff values by sex and age group. The diagnostic performance of each test varied by sex and age, and a diagnostic support tool was created to determine any abnormal results in a test. The calculated M/F cutoff values for GRT were as follows: 40–59 years, 21/18; 60–69 years, 17/17; 70–79 years, 15/15; and 80–89 years, 11/12. The calculated M/F cutoff values for grip strength 32/20, 29/13, 21/15, and 19/10. When either GRT or grip strength was judged as positive, the overall sensitivity was 88.2%, specificity was 78.1%, positive likelihood ratio was 4.03, and the negative likelihood ratio was 0.15. This novel diagnostic support tool was superior to using GRT and grip strength alone in the early DCM diagnosis. Future research to obtain age- and sex-specific data is necessary to validate and further improve the tool. [ABSTRACT FROM AUTHOR]

Background: Reduced core stability is a potential risk factor for low back pain in athletes. However, the association between core stability and low back pain in high school baseball players has not been thoroughly studied. The purpose of this study was to investigate the relationship between core stability and low back pain and its clinical characteristics in high school baseball players.Methods: Participants comprised 812 high school baseball players who had undergone annual medical evaluations, comprising a self-completed questionnaire and a physical examination. We investigated the relationships between low back pain during the season and on the day of medical evaluations and core stability using a cross-sectional study design. Core stability was assessed using the Sahrmann core stability test.Results: Reduced core stability was confirmed in 358 (44.1%) of all players, 98 (49.5%) pitchers, and 260 (42.3%) fielders. In total, 352 players (43.3%) reported incidents of seasonal low back pain during the previous year. Thirty-five pitchers (17.7%) and 153 fielders (24.9%) reported low back pain on the day of the medical evaluations. No significant associations were seen between low back pain throughout the season and reduced core stability. After adjusting for confounding factors (total amount of practice per week, hamstring tightness and quadriceps tightness) using logistic regression modeling, a significant association between presence of low back pain during lumbar extension movement and reduced core stability was found (odds ratio, 2.57; 95% confidence interval, 1.08-6.62; P = 0.033) in pitchers.Conclusions: High school baseball pitchers with reduced core stability showed a higher probability of reporting low back pain during lumbar extension movement. Evaluation of core stability should be considered in high school baseball players, especially in pitchers. [ABSTRACT FROM AUTHOR]

Metabolic syndrome and lumbar spinal stenosis (LSS) are common age-related diseases. However, the causal relationship between them remains unclear. This study aimed to identify the effects of LSS on metabolic syndrome incidence in community-dwelling adults. This prospective cohort study included participants of the Aizu cohort study (LOHAS) aged < 75 years as of 2008. Participants with metabolic syndrome at baseline were excluded. The primary outcome measure was metabolic syndrome incidence, and the main explanatory variable was the presence of LSS, as assessed by a self-reported questionnaire. A multivariate Cox proportional hazard regression model was used to estimate hazard ratios (HRs) for metabolic syndrome incidence during the 6-year follow-up period. Complete-case analyses were compared with the multiple imputation results. Among 1599 participants, 1390 complete cases were analyzed (mean [SD] age 62.3 [9.0] years; females, 734 [52.8%]). Among those participants, 525 (37.8%) developed metabolic syndrome during the follow-up of 3.89 [1.96] years. The presence of LSS was associated with developing metabolic syndrome (HR, 1.41; 95% confidence interval [CI] 1.02–1.95). Multiple imputation results showed similar trends of those having complete-case data (HR, 1.47; 95% CI 1.08–2.00). This finding suggests the importance of prevention and management of LSS in community settings. [ABSTRACT FROM AUTHOR]

Background: Lumbar spinal stenosis (LSS) is a clinical syndrome based on anatomic narrowing of the spinal canal. It is well known that anatomic narrowing of the spinal canal is essential for manifestation, but not all of them cause symptoms. There are many studies assessing the relationship between dural tube compression on MRI and clinical symptoms; however, most of them are cross-sectional. The purpose of this study was to reveal the magnitude of dural tube compression's influence on the presence or development of LSS symptoms at the six-year follow-up and the occurrence of surgery during the follow-up period or not in the community setting. Methods: This was a longitudinal observational study of 459 participants who were assessed for typical LSS symptoms, and whose Roland–Morris Disability Questionnaire and numerical rating scale of leg pain and numbness was recorded using a questionnaire and conventional MRI of the lumbar spine. Typical LSS symptoms were judged using an LSS diagnostic support tool, which was a self-administered, self-reported history questionnaire (LSS-SSHQ). After six years, 232 subjects (follow-up rate 50.5%) were followed-up with typical LSS symptoms using LSS-SSHQ by mail. The relationship between the magnitude of dural tube compression evaluated by dural tube cross-sectional area (DCSA) in the initial assessment and the time course of typical LSS symptoms for the six-year duration were analyzed. In addition, predictors of the presence of typical LSS symptoms at the six-year follow-up were assessed. Furthermore, we investigated the relationship between typical LSS symptoms and DCSA during the initial assessment of patients who underwent surgery during the follow-up period. A multivariate logistic regression analysis was performed for statistical analysis. Results: (1) Severe dural tube compression did not show that LSS symptoms continued after six years. (2) Severe dural tube compression could not detect development of LSS-symptoms and surgery during the six-year period. Conclusion: Severe dural tube compression could not detect typical LSS symptom development and occurrence of surgery during the six-year period. [ABSTRACT FROM AUTHOR]

Despite the applicability of the lumbar spinal stenosis (LSS)-diagnosis support tool (DST) and the LSS-self-administered, self-reported history questionnaire (SSHQ), their diagnostic accuracy has never been compared with that of the well-known North American Spine Society (NASS) clinical description of LSS. This study aimed to compare the diagnostic accuracy of the two diagnostic tools with that of the NASS guidelines' clinical description of LSS in a Japanese secondary care hospital setting. This multicenter cross-sectional study used data from the lumbar spinal stenosis diagnostic support tool (DISTO) project, which was conducted from December 1, 2011 to December 31, 2012. Japanese adults with low back pain (LBP) aged ≥20 years were consecutively included. The reference standard was LSS diagnosed by orthopedic physicians. The diagnostic accuracy of the two support tools was compared. Of 3,331 patients, 1,416 (42.5%) patients were diagnosed with LSS. The NASS clinical description of LSS had a sensitivity of 63.9% and specificity of 89.5%. The LSS-DST and LSS-SSHQ had sensitivities of 91.3% and 83.8% and specificities of 76.0% and 57.6%, respectively, with substantial improvements in sensitivity (P < 0.0001). Similar results were obtained when we limited included patients to those aged >60 years. These findings indicated that the LSS-DST and LSS-SSHQ were more sensitive in screening patients with LBP for a diagnosis of LSS than the NASS clinical description of LSS. This study strongly supports prioritizing the use of either of these two diagnostic support tools for screening. [ABSTRACT FROM AUTHOR]

Background: Limited flexibility of the lower extremities, such as hamstring tightness, has long been suggested as a physical risk factor for low back pain among adolescent athletes. However, few prospective cohort studies have examined the direction of causality for this relationship. This prospective cohort study investigated the relationship between limited flexibility of the lower extremities and the occurrence of low back pain among high school baseball players.Methods: Participants comprised 335 high school baseball players from 43 high school baseball teams who had undergone baseline medical evaluations (a self-completed questionnaire and physical examination). Occurrence of low back pain during a 1-year follow up, and associations with measurements of flexibility of the lower extremities such as straight-leg-raising angle (hamstring tightness), Thomas test (iliopsoas tightness), heel-buttock-distance (quadriceps tightness), and passive range of motion of the hip were investigated.Results: In total, 296 players (88.4%) participated in the 1-year follow-up survey, with 147 of the 296 players (49.7%) reporting the occurrence of low back pain during follow-up. The number of players with low back pain during follow-up peaked in November, then decreased and was lowest in June. After adjusting for factors associated with low back pain using logistic regression modeling, a significant association between hamstring tightness on the non-throwing arm side and low back pain (odds ratio 2.86, 95% confidence interval 1.17-6.94; P = 0.018) was found.Conclusions: Hamstring tightness on the non-throwing arm side was identified as a potential risk factor for low back pain in high school baseball players. These results may provide guidance in the development of future prevention programs. [ABSTRACT FROM AUTHOR]

Background: Sacroiliac joint (SIJ) dysfunction is a potential source of low back pain (LBP) in baseball players, who are more likely to be affected by loading of the SIJ in the throwing motion. However, the prevalence and characteristics of this condition have not been studied thoroughly. This study aimed to investigate the prevalence and clinical characteristics of SIJ dysfunction among high school baseball players.Methods: Participants comprised 891 high school baseball players who had undergone annual medical evaluations (a self-completed questionnaire and physical examination). The prevalence of SIJ dysfunction and associations with the measurements of the flexibility of the spine and lower extremities such as finger-floor-distance, straight-leg-raising angle, heel-buttock-distance, Thomas test, and passive range of motion of the hip were investigated.Results: Twenty-two of 891 subjects (2.5%) met our criteria for SIJ dysfunction. Twelve subjects (55%) exhibited throwing arm side symptoms more commonly than in the non-throwing arm side (n = 3, 15%) or bilateral side (n = 7, 32%). Previous episodes of LBP were experienced significantly more frequently among subjects with SIJ dysfunction (n = 19, 86.4%) than among those without (n = 501, 57.7%; P = 0.015). The prevalence of present LBP that interfered with play was significantly higher among subjects with SIJ dysfunction (n = 9, 42.9%) than among those without (n = 118, 21.2%; P = 0.038). The prevalence of SIJ dysfunction as a source of LBP was estimated at 7.1% (9 of 127 subjects). After adjustment for associated factors using a logistic regression model, we observed a significant association between a limitation in hip internal rotation on the throwing arm side and SIJ dysfunction (odds ratio 3.11 [1.30-7.71]; P = 0.0109).Conclusions: According to our criteria, the estimated prevalence of SIJ dysfunction among high school baseball players is 2.5%. There was a significant association between a limitation in hip internal rotation on the throwing arm side and SIJ dysfunction. [ABSTRACT FROM AUTHOR]

Background: Deterioration of quality of life in patients with chronic pain is difficult to treat. Chronic pain in patients with low quality of life may be "severe" and require multidisciplinary treatments. This study aimed to develop an objective severity discrimination scale based on quality of life measurements to identify patients with "severely disabling" chronic pain.Methods: Subjects were 156 patients with chronic pain whose numerical rating pain score was ≥1 and who had pain for ≥3 months. Diseases associated with chronic pain included spinal diseases, joint diseases, concomitant diseases, complex regional pain syndromes, and other musculoskeletal diseases. Patients were divided into low, middle, and high groups based on physical quality of life summary scores on the Short Form-36. The mental component summary, painDETECT, Japanese version of the Pain Catastrophizing Scale, Brief Scale for Psychiatric Problems in Orthopaedic Patients, and factors related to degree/quality of pain during the past 4 weeks were analyzed to identify components in the low group. The score weighting factor for discriminating between the high and low groups was determined by discriminant analysis.Results: Factor analysis identified 4 factors representing features of chronic pain patients with low QOL: enhanced perception of pain, pain catastrophic thoughts, depressive sleep disorder, and pain intensity. For discriminant analysis, patients were defined as those with low physical quality of life if each factor's total score multiplied by a factor plus a constant value of 2.6 was ≥0, and high quality of life if it was <0. The receiver operating characteristic curve area used to determine the cut-off value was 0.71, with 67.3% sensitivity and specificity.Conclusions: We developed a 33-question severity discrimination scale to define "severely disabling" chronic pain based on physical quality of life. "Severely disabling" patients identified on this scale could represent chronic pain patients needing focused multidisciplinary treatment. [ABSTRACT FROM AUTHOR]

The article presents a study on the interaction of 5-hydroxytryptamine (5-HT) with tumor necrosis factor (TNF) for pain related behavior in a model of rat lumbar disc herniation (LDH). There were six groups of adult female Sprague-Dawley rats. It was found that 5-HT and TNF both induce pain-related behavior and interact with one another to prolong pain-related behavior in the model.

The article presents a study on pain mechanisms through introduction of nucleus pulposus (NP) in the dorsal root ganglion (DRG) of rats. It says that immunohistochemistry and immunoblotting were performed on rats to determine the action of NP and tumor necrosis factor-alpha (TNF-α). Pain-related behavior was noted to originate from activation of macrophages and glial cells in DRG. It concludes that neuropathic pain states are associated with activities of macrophages and glial cells.

The article presents a study which observes the reaction of glial cells and endoneural macrophages positioned in the dorsal root ganglion in rats. It states that activated satellite glial cells expressed glial cell-line derived neurotrophic factor (GDNF) which expression thereof was significantly increased and persisted for 28 days. Results show that mechanical withdrawal threshold was significantly decreased for 28 days.

Altered dorsal root ganglion (DRG) function is associated with neuropathic pain following spinal nerve injury. However, compression of the cauda equina and dorsal rhizotomy proximal to the DRG do not induce significant pain, whereas in the spinal nerve and peripheral nerve, injury distal to the DRG does induce neuropathic pain. Caspase signaling induces apoptosis, and caspase inhibitors prevent pain-related behavior. The degree of DRG neuronal apoptosis is thought to play a role in pain behavior. We suggest that differences in pain behavior according to the injury sites within the DRG may be related to imbalances in apoptotic injuries. The aim of this study was to determine which compression injury was more painful and to compare behavior with expression of tumor necrosis factor (TNF)-alpha in DRG and apoptosis in the DRG following crush injury to the L5 nerve root or L5 spinal nerve. Sprague–Dawley rats received a crush injury to the L5 spinal nerve (distal to the DRG), crush injury to the L5 nerve root (proximal to the DRG), or no crush injury (sham). Mechanical allodynia was determined by the von Frey test. Expression of TNF-alpha was compared among three groups using immunoblot findings. Furthermore, we compared the percentage of neurons injured in the DRG using immunostaining for apoptotic cells and localization of activated caspase 3. Mechanical allodynia was observed in both crush injury groups. The duration of mechanical allodynia in the distal crush group was significantly longer than in the proximal crush group ( P < 0.05). TNF-alpha expression was increased in DRG neurons following injury. DRG apoptosis in the distal crush group was significantly higher than in the proximal group at each time point ( P < 0.05). This study suggests that spinal nerve crush injuries produce a greater degree of DRG apoptosis than do corresponding nerve root crush injuries, and that the former injuries are associated with longer lasting mechanical allodynia. Thus, differences in the time course of mechanical allodynia might be associated with an imbalance in DRG apoptosis. [ABSTRACT FROM AUTHOR]

The article offers information on the effect of cilostazol on nerve conduction velocity (NCV) and blood flow. A study was conducted to determine the effects of cilostazol on NCV and blood flow in acute and chronic cauda equina compression. The study revealed that cilostazol improved the reduction of NCV and blood flow.

The article reports on the evaluation of the effects of exogenous five-hydroxytryptamine (5-HT) applied on the nerve root on pain-related behavior, the release of endogenous 5-HT in plasma and the expression of receptors in dorsal root ganglion in a rat lumbar disc hermiation model. Exogenous 5-HT to the nerve root induced pain-related behavior compared with the nucleus pulposus application.

The article presents a medical research on compensatory neovascularization after cauda equina compression in rats. The study observed the ischemic changes in the cauda equina after surgery and the increased expression of vascular endothelial growth factor (VEGF) and neovascularization. It revealed that cauda equina compression seems to induce compensatory neovascularization accompanied by an increase in VEGF expression.

Background: External medication that is absorbed percutaneously may be used to reduce inflammation and relieve pain from acute injuries such as ankle sprains and bruises. The plaster method of percutaneous absorption for non-steroidal anti-inflammatory drugs (NSAIDs) was established in Japan in 1988. However, due to the possibility of a placebo effect, the efficacy of this method remains unclear. This experimental study was conducted to control for the placebo effect and to study the efficacy of the plaster method in relieving pain by using a rat model of inflammation. Methods: Male Wistar-Imamichi rats were used. A yeast suspension was injected into the right hind paw to induce inflammation. A sheet (2.0 x 1.75 cm) containing the drug was adhered to the inflamed paw. Five treatment groups were used, and each sheet contained a single drug: loxoprofen sodium (loxoprofen-Na) (2.5 mg); felbinac (1.75 mg); indomethacin (1.75 mg); ketoprofen (0.75 mg); or base only (control, 0 mg). Mechanical pain threshold, expression of c-Fos in the dorsal horn, and amount of prostaglandin (PG) E2 in the inflamed paw were evaluated. Results: Pain threshold increased after treatment, and was significantly increased in the loxoprofen-Na group compared with the control group (p < 0.05). Amounts of PGE2 were significantly decreased in the loxoprofen-Na and indomethacin groups compared with the control group (p < 0.05). Expression of c-Fos was significantly decreased in the loxoprofen-Na group compared with the control group (p < 0.05). Conclusion: Percutaneously absorbed NSAIDs have an analgesic effect, inhibit expression of c-Fos in the dorsal horn, and reduce PGE2 in inflamed tissue, indicating the efficacy of this method of administration for acute inflammation and localized pain. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether abnormalities of the sagittal modifiers (SMs) of the Scoliosis Research Society (SRS)-Schwab classification truly reflect back pain (BP)-specific quality of life (QOL), it is necessary to examine their dose–response relationships and to determine clinically impactful thresholds for declines in BP-specific QOL. This study aimed to analyse the continuous dose–response relationship between each SM and BP-specific QOL. Methods: This cross-sectional study, using data from a Japanese population-based cohort study, included 519 community-dwelling residents aged ≥ 50 years who participated in the annual health examination. The participants completed the Roland–Morris Disability Questionnaire (RDQ) on BP-specific QOL. Spino-pelvic alignment based on SMs was assessed by whole-spine X-ray examinations. We fitted general linear models with or without nonlinear terms to estimate the dose–response relationship between each SM and BP-specific QOL. Results: Pelvic tilt, pelvic incidence minus lumbar lordosis (PI-LL), and sagittal vertical axis showed dose–response relationships with BP-specific QOL measured as the RDQ score. PI-LL was most likely to predict a minimally clinically important RDQ score when its value exceeded the 90th percentile. A nonlinear relationship between PI-LL and the BP-specific QOL score was found. RDQ increased when PI-LL exceeded 10°. Conclusion: PI-LL might be the most sensitive of the three modifiers of the SRS-Schwab classification for determining BP-specific QOL. Moreover, BP-specific QOL worsens rapidly when the compensatory mechanism against malalignment exceeds a critical value. Therefore, we suggest that traditional classifications and surgical strategies should be re-examined regarding the dose-dependent abnormalities of the SMs to develop a more reliable classification strategy. [ABSTRACT FROM AUTHOR]

Purpose: With spinal deformities, mental health can deteriorate due to sagittal imbalance of the spine. The purpose of this study was to clarify the relationship between sagittal imbalance and symptoms of depression among local residents in the community. Methods: This study used data from the Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS) in 2010. The sagittal vertical axis (SVA) was identified as an indicator of sagittal imbalance. Symptoms of depression were assessed using the 5-item version of the Mental Health Inventory. Participants were classified into three categories based on the SVA balance as normal (< 40 mm), moderate imbalance (40–95 mm), and severe imbalance (> 95 mm). To evaluate the relationship between sagittal imbalance of the spine and symptoms of depression, the adjusted risk ratio (RR) and the 95% confidence interval (CI) were calculated using a generalized linear model with Poisson link. Results: There were 786 participants included in the statistical analysis. Overall, the mean age was 68.1 y (standard deviation, 8.8 y), and 39.4% were men. The prevalence of symptoms of depression by SVA category was 18.6% for normal, 23.8% for moderate, and 40.6% for severe. On multivariate analysis, the RR of SVA for symptoms of depression compared to the normal category was 1.12 (95% CI 0.7–1.70) for the moderate category and 2.29 (95% CI 1.01–5.17) for the severe category. Conclusion: In local community residents, sagittal imbalance had a significant association with symptoms of depression. [ABSTRACT FROM AUTHOR]

Background: Degenerative compressive myelopathy (DCM) is caused by cervical cord compression. The relationship between the magnitude and clinical findings of cervical cord compression has been described in the literature, but the details remain unclear. This study aimed to clarify the relationship between the magnitude and clinical symptoms of cervical cord compression in community-dwelling residents. Methods: The present study included 532 subjects. The subjective symptoms and the objective findings of one board-certified spine surgeon were assessed. The subjective symptoms were upper extremity pain and numbness, clumsy hand, fall in the past 1 year, and subjective gait disturbance. The objective findings were: Hoffmann, Trömner, and Wartenberg signs; Babinski's and Chaddock's signs; hyperreflexia of the patellar tendon and Achilles tendon reflexes; ankle clonus; Romberg and modified Romberg tests; grip and release test; finger escape sign; and grip strength. Using midsagittal T2-weighted magnetic resonance imaging, the anterior–posterior (AP) diameters (mm) of the spinal cord at the C2 midvertebral body level (DC2) and at each intervertebral disc level from C2/3 to C7/T1 (DC2/3-C7/T1) were measured. The spinal cord compression ratio (R) for each intervertebral disc level was defined and calculated as DC2/3-C7/T1 divided by DC2. The lowest R (LR) along C2/3 to C7/T1 of each individual was divided into 3 grades by the tertile method. The relationship between LR and clinical symptoms was investigated by trend analysis. Results: The prevalence of subjective gait disturbance increased significantly with the severity of spinal cord compression (p = 0.002812), whereas the other clinical symptoms were not significantly related with the severity of spinal cord compression. Conclusions: The magnitude of cervical cord compression had no relationship with any of the neurologic findings. However, subjective gait disturbance might be a better indicator of the possibility of early stage cervical cord compression. [ABSTRACT FROM AUTHOR]

Study Design: The relation between the rib head and the thoracic disc was investigated anatomically.Objectives: To clarify the necessity of rib head resection in thoracoscopic discectomy using the anterior approach.Summary Of Background Data: When using the transthoracic anterior approach, the rib head must often be resected. However, there are no reports in which the relation between the rib head and the interspinal disc has been investigated.Methods: The distance between the inferior margin of the superior vertebral body and the superior margin proximal to the rib (hereafter, "rib index") was measured.Results: The rib index shows negative value in T2-T9 levels, while zero in Tl0 level and positive value T11-T12. The rib index of the fifth to ninth ribs in men was significantly smaller than those in women.Conclusions: The surgeon should anticipate full removal of the rib head if operating at T9 and only partial resection below that level. [ABSTRACT FROM AUTHOR]

Objectives To examine the longitudinal association between baseline disability due to low back pain (LBP) and future risk of falls, particularly significant falls requiring treatment, in a community-dwelling older population. Methods This was a prospective population-based cohort study using data from the Locomotive Syndrome and Health Outcomes in Aizu Cohort Study (LOHAS; 2008–2010). A total of 2,738 residents aged ≥60 years were enrolled. LBP was assessed using the Roland-Morris Disability Questionnaire (RMDQ), and the level of LBP-related disability was divided into three categories (none, low, and medium to high). Incidence of falls over the following year was determined using a self-reported questionnaire after the one-year follow-up period. The risk ratio (RR) for LBP-related disability associated with any fall and any fall requiring treatment was estimated using log binomial regression models. Results Data were analyzed for 1,358 subjects. The prevalence of LBP at baseline was 16.4%, whereas 122 (8.9%) participants reported a low level of LBP-related disability and 101 (7.4%) reported medium to high levels of LBP-related disability. Incidence of any fall and falls requiring treatment was reported by 22.1% and 4.6% of participants, respectively. Subjects with medium to high levels of disability were more likely to experience subsequent falls (adjusted RR = 1.53, 95% confidence interval [CI] = 1.21–1.95) and falls requiring treatment (adjusted RR = 2.55, 95% CI = 1.41–4.60) than those with no LBP-related disability. Conclusions Level of LBP-related disability was associated with an increased risk of serious falls in a general population of community-living older adults. These findings can alert health care providers involved in fall prevention efforts to the important issue of activity-related disability due to LBP. [ABSTRACT FROM AUTHOR]

Background: The reference values of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) in patients with lumbar spinal stenosis (LSS) are still unknown. This multicenter cross-sectional survey was performed to determine the reference values and disease-specific characteristics of deterioration of QOL caused by LSS itself, not by aging, through comparison of patients with and without LSS who had an outpatient visit for low back pain by age and sex groups.Methods: The present study was performed at 564 medical centers and clinics. The JOABPEQ was measured for 8338 patients aged 20 years or over who came to an outpatient clinic for low back pain (LBP) and were examined for whether they had LSS using the LSS diagnosis support tool (LSS-DST). Scores in the five JOABPEQ domains were compared between the LSS group and the LBP without LSS group (LBP group) for each age and sex group.Results: Scores for Pain-related disorder, Gait disturbance, Social life disturbance, and Psychological disorders were significantly lower in the LSS group than in the LBP group.Conclusion: The percentiles of JOABPEQ scores in patients with LSS were clarified and could be used as reference values. Deterioration of QOL caused by LSS itself, not by aging, are characterized by Pain-related disorder, Gait disturbance, Social life disturbance, and Psychological disorders. [ABSTRACT FROM AUTHOR]

Study Design: Controlled, interventional, animal study.Objective: To investigate the spatial and temporal changes of μ-opioid receptor (MOR) expression in a rat lumbar disc herniation (LDH) model.Summary Of Background Data: MORs widely express in the peripheral and central nervous systems, and opioid drugs produce an analgesic effect through their activation. However, the efficacy of opioid drugs is sometimes inadequate in several pathological conditions of pain. MORs in the brain as well as the spinal cord (SC) and dorsal root ganglion (DRG) are thought to be associated with pain-related behavior, but the underlying mechanisms are not completely understood.Methods: In all, 91 adult female Sprague-Dawley rats were used. Autologous nucleus pulposus (NP) was applied onto the left L5 DRG in the NP group rats. Rats were divided into two surgical groups, the NP and the sham group. The von Frey test of left hind paw was performed before surgery, and 2, 7, 14, 21 and 28 days after surgery. Immunohistochemistry and immunoblotting in the DRG, SC, Caudate putamen, nucleus accumbens (NAc) and periaqueductal grey matter were performed before surgery, and 2, 7, 14, 21 and 28 days after surgery.Results: The thresholds in the NP group were significantly lower than those in the sham group from day 2 onwards. At days 7 and 14, MOR expression in the injured-side SC and DRG were significantly lower than those in the sham group. At day 21, MOR in the NAc was significantly decreased compared to that in the sham group.Conclusion: Changes of MOR expression in the NAc, SC and DRG were associated with pain-related behavior. This result might show the underling pathogenesis of the resistance to MOR agonists in the patient with LDH.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

Background: In 1999, the Japanese Orthopaedic Association decided to develop a new Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The final version of the JOACMEQ, comprising 24 questions and five domains (cervical spine function (CF); upper extremity function (UF); lower extremity function (LF); bladder function (BF); and quality of life (QOL)), was established after three nationwide investigations. The fourth investigation, reported in this paper, was performed to confirm the responsiveness of the questionnaire.Methods: A total of 137 patients with cervical myelopathy were included in the study. Each patient was interviewed twice using the JOACMEQ before and after treatment. At the second interview, the patients self-rated their condition in five domains for "worse," "somewhat worse," "no change," "somewhat better," or "better," and these scores were defined as the external assessment rating. The difference of the points in five domains between the first and the second interview was calculated against each external assessment. Based on the results, substantial clinical benefit (SCB) thresholds for the JOACMEQ were determined.Results: The statistically significant median values of the acquired points were 17.5 for CF, 16.0 and 21.0 for UF, 27.0 and 20.5 for LF, 13.0 for BF, and 29.0 for QOL. After consideration of the results, the committee decided that an acquired point ≥20 could be interpreted as representing an SCB threshold for the JOACMEQ.Conclusion: We have concluded that a treatment can be judged to be effective for a patient if 1) The patient give all answers for the questions necessary to calculate the functional score of a domain and an increase of ≥20 points is obtained for that score, or 2) The functional score after treatment is > 90 points even if the answer for the unanswered questions was supposed to be the worst possible choice. [ABSTRACT FROM AUTHOR]

Background: Inadequate sleep is correlated with morbidity and mortality among older adults. However, the longitudinal relationship between subjective sleep quality and risk of falls in the elderly population remains to be clarified.Methods: Study participants were from Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) sites (1,071 community-dwelling people ≧65 years of age, mean: 71 years). Subjective sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI). Occurrence of falls (defined as experiencing at least one fall) during the subsequent year was ascertained by a self-reported questionnaire.Results: Mean global PSQI score was 4.3 (SD 3.2), with 28.9% of participants rating their sleep quality as poor (PSQI > 5). A total of 210 participants (19.6%) fell at least once in the year following sleep examination. Multivariable analysis revealed that participants reporting worse subjective sleep quality had significantly higher odds of experiencing falls during the 1-year follow-up period (adjusted odds ratio [AOR] = 1.50 for each three-point increase in global PSQI score; 95% confidence interval [CI] = 1.20, 1.89). Participants in the highest global PSQI score (PSQI > 5) quartile had significantly increased odds of experiencing falls compared to those in the lowest global score quartile (PSQI < 2; AOR = 2.14; 95% CI = 1.09, 4.22). This association was similarly significant in subgroup analyses for older men and women, nonusers of sleep medication, and those without a history of falls at baseline.Conclusion: Subjective poor sleep quality, as measured by the PSQI, is longitudinally associated with greater risk of experiencing falls in community-dwelling older adults. [ABSTRACT FROM AUTHOR]

Background The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) was developed in 2007, including the five domains of Pain-related disorder, Lumbar spine dysfunction, Gait disturbance, Social life disturbance, and Psychological disorder. It is used by physicians to evaluate treatment efficacy by comparing scores before and after treatment. However, the JOABPEQ does not allow evaluation of the severity of a patient's condition compared to the general population at a single time point. Given the unavailability of a standard measurement of back pain, we sought to establish reference scores and interquartile ranges using data obtained from a multicenter, cross-sectional survey taken in Japanese primary care settings. Methods The Lumbar Spinal Stenosis Diagnosis Support Tool project was conducted from 2011 to 2012 in 1657 hospitals in Japan to investigate the establishment of reference scores using JOABPEQ. Patients aged ≥ 20 years undergoing medical examinations by either non-orthopaedic primary care physicians or general orthopedists were considered for enrollment. Results A total of 10,651 consecutive low back pain patients (5331 men, 5320 women, 18 subjects with missing sex data) who had undergone a medical examination were included. Reference scores and interquartile ranges for each of the five domains of the JOABPEQ according to age and sex were recorded. The median score and interquartile range are the same in the domain of Pain-related disorder in all ages and sexes. The reference scores for Gait disturbance, Social life disturbance and Psychological disorder declined with increasing age in both age- and sex-stratified groups, while there was some different trend in Lumbar spine dysfunction between men and women. Conclusion Reference scores and interquartile ranges for JOABPEQ were generated based on the data from the examination data. These provide a measurement standard to assess patient perceptions of low back pain at any time point during evaluation or therapy. [ABSTRACT FROM AUTHOR]

Study Design: An experimental animal study.Objective: To investigate the relationship between pain-related behavior and the expression of neurotrophic factors in the dorsal root ganglion (DRG) and spinal cord (SC) using a nucleus pulposus (NP) rat model.Summary Of Background Data: Neurotrophic factors are released from activated glial cells and are associated with pain-related behavior. Nerve growth factor (NGF) is a neurotrophic factor that is induced by inflammation.Methods: Rats were divided into an NP group (n = 94) and a sham-operated group (n = 46). NP harvested from the tail was applied to the left L5 DRG. Rats in the NP group were then divided into five subgroups: one non-treatment and four treatment groups. In the treatment groups, a dose of anti-NGF antibody or phosphate-buffered saline was administered into the DRG. Behavioral testing was performed to investigate the mechanical withdrawal threshold of the left hind paw for all groups. Immunohistochemical localization of NGF, phosphorylated p38 (p38), and brain-derived neurotrophic factor (BDNF) in the DRGs and SCs was performed, and the numbers of immunoreactive (IR) cells were counted.Results: The withdrawal threshold in the nontreatment NP group was significantly decreased for 35 days, and that of the middle- and high-dose treatment rats was significantly higher than the phosphate-buffered saline group values. In the DRG, NGF-IR, p38-IR, and BDNF-IR cells were increased for days 21. In the SC, BDNF-IR, and p38-IR cells were increased from days 7 to 21.Conclusion: In the DRG, NGF expression increased, mechanical thresholds were reduced, and p38 and BDNF expression was increased in the NP group. p38 and BDNF expression was increased in SC neurons during the same period. Inhibition of NGF may be a potential treatment for neuropathic pain due to lumbar disc herniation.Level Of Evidence: 5. [ABSTRACT FROM AUTHOR]

Study Design: A controlled, interventional animal study.Objective: The aim of this study was to evaluate the effect of diabetes mellitus (DM) on radiculopathy due to lumbar disc herniation (LDH), by investigating pain-related behavior and the expression of tumor necrosis factor-alpha (TNF-α) and growth-associated protein 43 (GAP43) in type 2 diabetic rats following application of nucleus pulposus (NP) to the dorsal root ganglion (DRG).Summary Of Background Data: Previous clinical studies suggested negative effects of DM on radiculopathy due to LDH, and that inflammation and nerve regeneration could interact with DM and radiculopathy.Methods: We applied autologous NP to the left L5 DRG of adult male Wistar rats and Goto-Kakizaki rats. Behavioral testing measured the mechanical withdrawal threshold of rats. We immunohistochemically evaluated the localization of ionized calcium-binding adapter molecule-1 (Iba-1), receptor of advanced glycation end products (RAGE), and TNF-α in DRGs. TNF-α and GAP43 expression levels in DRG were determined by quantitative real-time PCR and western blotting.Results: The mechanical withdrawal threshold significantly declined in the non-DM NP group compared with the non-DM sham group for 28 days, whereas the decline in threshold extended to 35 days in the DM NP group compared with the DM sham group. RAGE and TNF-α expression in DRGs was colocalized in Iba-1 positive cells. The non-DM NP rats had higher TNF-α protein expression levels versus the non-DM sham rats on day 7, and the DM NP group had higher levels versus the DM sham group on days 7 and 14. The non-DM NP group had higher GAP43 mRNA expression than the non-DM sham group for 28 days, while the DM NP group had a higher level than the DM sham group for 35 days.Conclusion: DM prolongs the pain-related behavior caused by NP. The prolonged inflammation and nerve regeneration could elucidate the pathogenesis of continuous pain of radiculopathy initiated by LDH.Level Of Evidence: N /A. [ABSTRACT FROM AUTHOR]