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Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Diffuse idiopathic skeletal hyperostosis (DISH) frequently occurs in the spine, resulting in unstable fractures. Treating thoracolumbar fractures in patients with DISH is often difficult because the anterior opening of the vertebral body is exacerbated by dislocation in the prone position, making reduction difficult. In this study, we introduced a novel skull clamp-assisted positioning (SAP) technique. The patient is placed in a supine position with a skull clamp used in cervical spine surgery before surgery to prevent the progression of dislocation and to restore the patient's position. Using this method, the mean difference in local kyphosis angle improved from -2.9 (±8.4)° preoperatively to 10.9 (±7.7)° postoperatively. Furthermore, posterior displacement decreased from a preoperative mean of 5.5 (±4.3) mm to 0.3 (±0.7) mm postoperatively. Complications such as neurological sequelae, implant fracture, and surgical site infection were not observed through one year of postoperative follow-up. SAP may decrease invasiveness and complications. Longer-term studies and larger sample sizes are needed to establish long-term efficacy and benefits.

Background : In the diagnosis of lumbar spinal stenosis (LSS), finding stenosis with magnetic resonance imaging (MRI) does not always correlate with symptoms such as sciatica or intermittent claudication. We perform decompression surgery only for cases where the levels diagnosed from neurological findings are symptomatic, even if multiple stenoses are observed on MRI. The objective of this study was to examine the time course of asymptomatic stenosis in patients with LSS after they underwent decompression surgery for symptomatic stenosis. Materials and Methods : The participants in this study comprised 137 LSS patients who underwent single-level L4-5 decompression surgery from 2003 to 2013. The dural sac cross-sectional area at the L3-4 disc level was calculated based on preoperative MRI. A cross-sectional area less than 50 mm 2 was defined as stenosis. The patients were grouped, according to additional spinal stenosis at the L3-4 level, into a double group (16 cases) with L3-4 stenosis, and a single group (121 cases) without L3-4 stenosis. Incidences of new-onset symptoms originating from L3-4 and additional L3-4-level surgery were examined. Results : Five years after surgery, 98 cases (72%) completed follow-up. During follow-up, 2 of 12 patients in the double group (16.7%) and 9 of 86 patients in the single group (10.5%) presented with new-onset symptoms originating from L3-4, showing no significant difference between groups. Additional L3-4 surgery was performed for one patient (8.3%) in the double group and three patients (3.5%) in the single group; again, no significant difference was shown. Conclusion : Patients with asymptomatic L3-4 stenosis on preoperative MRI were not prone to develop new symptoms or need additional L3-4-level surgery within 5 years after surgery when compared to patients without preoperative L3-4 stenosis. These results indicate that prophylactic decompression for asymptomatic levels is unnecessary.

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., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Numbness in the soles of both feet at rest or bowel/bladder dysfunction can occur in patients with lumbar spinal stenosis (LSS), especially in patients with cauda equina lesions. The purpose of this study was to clarify the relationship between cauda equina symptoms at rest and quality of life (QOL) in LSS patients using standardized questionnaires developed for the Japanese population., Methods: A survey was conducted in 564 hospitals and general practice clinics nationwide from December 1, 2011 to December 31, 2012. All patients who visited hospital or clinic because of low back pain were included. Patients were diagnosed with LSS using the LSS-Diagnostic Support Tool (LSS-DST), and the severity of the disease was measured using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) for quality of life. Presence of both sole numbness and/or bowel/bladder dysfunction were determined by medical interview. 3647 patients were diagnosed with LSS according to the results of the LSS-DST. 1294 of these patients (35.5%) had symptoms at rest. Of these patients, 359 patients with sole numbness, 135 patients with bowel/bladder dysfunction, and 52 patients with both numbness and bowel/bladder dysfunction were compared to the patients without rest symptoms (n = 2182). Comparisons between groups with or without sole numbness and bowel/bladder dysfunction were performed using statistical analysis of JOABPEQ responses in the categories of pain-related disorder, lumbar spine disorder, gait disturbance, social life disturbance, and psychological disorder., Results: All groups with sole numbness and/or bowel/bladder dysfunction had statistically lower (worse) scores in all categories of the JOABPEQ compared to the group without these symptoms at rest., Conclusion: LSS patients having numbness in the soles of both feet at rest or bowel/bladder dysfunction had lower measurements of QOL and activities of daily living than those patients without symptoms at rest. These symptoms appear to be related to QOL of LSS patients., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Study Design: A cross-sectional study of 1804 consecutive patients., Objective: The aim of this study was to investigate the prevalence of pathological pain and its distribution features in patients with chronic lumbar spinal disorders., Summary of Background Data: Clinical spinal disorders can involve pathological neuropathic pain (NeP) as well as physiological nociceptive pain (NocP), as they have varied pathology, including spinal cord injury, stenosis, and compression. A study conducted by the Japanese Society for Spine Surgery and Related Research (JSSR) has determined a prevalence of 29.4% for NeP in patients with lumbar spinal disorder. However, the data did not include information on pain location., Methods: Patients aged 20 to 79 years with chronic lower back pain (≥3 months, visual analog scale score ≥30) were recruited from 137 JSSR-related institutions. Patient data included an NeP screening questionnaire score and pain location (lower back, buttock, and legs). The association between the pain pathology and its location was analyzed statistically using the unpaired t test and Chi-square test followed by Fisher test. P < 0.05 was considered significant., Results: Low back pain subjects showed 31.9% of NeP prevalence, and the pain distribution showed [NocP(%)/NeP(%)] low back pain only cases: 44/22, while low back pain with leg pain cases showed a prevalence of 56/78. This indicates that low back pain alone can significantly induce NocP rather than NeP (P < 0.01). Buttock pain was revealed to significantly induce both lower back pain and leg pain with NeP properties (P < 0.01). Leg pain was revealed to be predominantly neuropathic, especially when it included peripheral pain (P < 0.01)., Conclusion: Low back pain with no buttock pain induces NocP rather than NeP. Buttock pain is significantly associated with NeP prevalence whether or not leg pain exists. Leg pain can increase the prevalence of NeP, especially when it contains a peripheral element., Level of Evidence: 3.

Introduction: Lumbar spinal stenosis (LSS) is a lumbar spinal disorder that causes leg symptoms and intermittent claudication. It is reported that the risk factors for low back pain include age, family history, smoking, obesity, work-related physical load, exercise, and depression. This was a multicenter, cross-sectional survey, and the aim of this study was to investigate the prevalence of LSS by age and the relationships between LSS and psychosocial factors and job satisfaction., Methods: This study enrolled subjects aged 50 years and over from a survey of LSS in 2177 hospitals and general practices nationwide. The clinical characteristics of the LSS and non-LSS groups were compared using the χ2 test, and the multivariate logistic regression analysis was performed to examine associations between exercise, perceived stress, strenuous use of the low back or legs, job satisfaction, and LSS., Results: In total, 18,642 patients (8338 males, 10,267 females) were analyzed. The rate of LSS was 38.3% and it increased with age. Regular exercise was less common among those in the LSS group than those in the non-LSS group (p<0.001). Satisfaction in all job-related items was less in the LSS group than in the non-LSS group (p<0.001). The odds for having LSS were higher in subjects having perceived stress and strenuous use of the low back or legs (p=0.001). The odds ratios of heart diseases and hypertension (p<0.001) were higher in the LSS group., Conclusion: This study investigated factors associated with LSS. The prevalence of LSS increased with age. Perceived stress and strenuous use of the low back or legs might be associated with LSS, and job satisfaction was lower with LSS.

Background: Diagnostic support tools for lumbar spinal stenosis such as the Self-administered, Self-reported History Questionnaire have been developed in Japan, but no report has demonstrated the diagnostic accuracy of this questionnaire in Japanese primary care settings. This multicenter, cross-sectional survey was performed to evaluate and improve the diagnostic accuracy of this questionnaire for lumbar spinal stenosis patients in Japanese primary care settings., Methods: The lumbar spinal stenosis diagnosis support tool project was conducted in 1657 hospitals to evaluate the diagnostic accuracy of the Self-administered, Self-reported History Questionnaire in Japan from 2011 to 2012. Consecutive adults (≥50 years old) from physicians, including non-orthopedic general practitioners and orthopedic general practitioners, were considered for enrollment. Consecutive adults (≥50 years old) with low back pain from hospital-based orthopedic surgeons were also considered for enrollment. The diagnostic accuracy of the Self-administered, Self-reported History Questionnaire with initial and several new cutoff points in classifying patients according to the presence of lumbar spinal stenosis was assessed in terms of sensitivity, specificity and negative predictive values., Results: Among the 33,545 patients, 10,199 (30.4 %) were diagnosed with lumbar spinal stenosis by the physicians. The Self-administered, Self-reported History Questionnaire version 1.1 with a new cutoff point was more sensitive than the Self-administered, Self-reported History Questionnaire version 1.0 with the initial cutoff point (79.8 vs. 68.3 %) and less specific (68.8 vs. 75.1 %) for lumbar spinal stenosis diagnosis. The respective negative predictive values were 88.5 and 84.3 %., Conclusions: The Self-administered, Self-reported History Questionnaire version 1.1 with the new cutoff was more sensitive and had higher negative predictive value than version 1.0 with the initial cutoff. Therefore, the improved Self-administered, Self-reported History Questionnaire version 1.1 can be used for lumbar spinal stenosis screening, and its use may improve the quality of lumbar spinal stenosis diagnostic practice in Japanese primary care settings.

Study Design: Cross-sectional study., Objectives: To test the validity and responsiveness of the lumbar spinal stenosis (LSS)-specific symptom scale (FLS-25 [Fukushima LSS Scale 25])., Summary of Background Data: The FLS-25, a self-administered questionnaire designed to comprehensively cover various symptoms of LSS, has been developed to address the need to measure symptoms specific to this disorder., Methods: One hundred sixty-seven patients with confirmed LSS who required conservative therapy were asked to complete a questionnaire including questions regarding walking capacity and the FLS-25. These patients also underwent a lumbar extension test and a walking stress test, which are stress tests designed to objectively evaluate LSS symptoms, to measure standing time, walking distance, and walking time. Relationship between the FLS-25 scores and these external standards was analyzed to evaluate the criterion validity of the FLS-25. The patients underwent the same evaluations after 8 weeks of conservative therapy. The relationship between changes from baseline to week 8 in FLS-25 scores and changes in the 3 external standards was analyzed to evaluate the responsiveness of the FLS-25., Results: The distribution of FLS-25 scores among patients was symmetric, and there were no ceiling or floor effects. FLS-25 scores increased as self-reported walking capacity decreased (P=0.006). The mean standing time in the lumbar extension test was 165 (SD=109) seconds, and FLS-25 scores increased as standing time decreased (P=0.003). In the walking stress test, mean walking distance and mean walking time were 213 (SD=154) m and 236 (SD=114) seconds. FLS-25 scores increased as walking distance (P=0.002) and walking time (P=0.054) decreased. Changes from baseline to week 8 in FLS-25 scores correlated with changes in the stress test standing time (P=0.014), walking distance (P<0.001), and walking time (P<0.001)., Conclusion: The criterion validity and responsiveness of the FLS-25 were confirmed. The use of FLS-25 in clinical and investigational settings is warranted to monitor patients and evaluate therapeutic efficacy., Level of Evidence: 3.

Background: Pregabalin is a well-accepted treatment option for patients with neuropathic pain. However, the therapeutic efficacy of pregabalin for reducing the incidence of spinal surgery to treat leg symptoms in patients with lumbar spinal stenosis remains unknown. The purpose of this study was to analyze the therapeutic efficacy of pregabalin for reducing the incidence of spinal surgery for leg symptoms in patients with lumbar spinal stenosis during the first year of treatment., Methods: Consecutive patients diagnosed with lumbar spinal stenosis at our hospital from January to June 2009 were treated with nonsteroidal anti-inflammatory drug monotherapy and formed the control group (n = 47; 22 males, 25 females). Patients diagnosed with lumbar spinal stenosis at our hospital between August 2010 and October 2011 were treated with a nonsteroidal anti-inflammatory drug and pregabalin combination therapy and formed the pregabalin group (n = 49; 27 males, 22 females). The proportions of patients who underwent spinal surgery during the first year of treatment were assessed and compared between the two groups using the Mann-Whitney U test. In addition, the periods in which patients decided to undergo spinal surgery were compared using the Kaplan-Meier method., Results: Six patients (12.2%) in the pregabalin group and 22 patients (46.8%) in the control group underwent spinal surgery during the first year of treatment (P = 0.0035). The period in which patients decided to undergo spinal surgery was significantly delayed in the pregabalin group compared with the control group in those for whom spinal surgery was necessary (P = 0.0128)., Conclusions: Nonsteroidal anti-inflammatory drug and pregabalin combination therapy may result in a lower incidence of spinal surgery during the first year of treatment or a delayed period before undergoing spinal surgery if necessary compared with nonsteroidal anti-inflammatory drug monotherapy in patients with leg symptoms caused by lumbar spinal stenosis.

Background: The gait-loading test is a well known, important test with which to assess the involved spinal level in patients with lumbar spinal stenosis. The lumbar extension-loading test also functions as a diagnostic loading test in patients with lumbar spinal stenosis; however, its efficacy remains uncertain. The purpose of this study was to compare the diagnostic value of the lumbar extension-loading test with that of the gait-loading test in patients with lumbar spinal stenosis., Methods: A total of 116 consecutive patients (62 men and 54 women) diagnosed with lumbar spinal stenosis were included in this cross-sectional study of the lumbar extension-loading test. Subjective symptoms and objective neurological findings (motor, sensory, and reflex) were examined before and after the lumbar extension-loading and gait-loading tests. The efficacy of the lumbar extension-loading test for establishment of a correct diagnosis of the involved spinal level was assessed and compared with that of the gait-loading test., Results: There were no significant differences between the lumbar extension-loading test and the gait-loading test in terms of subjective symptoms, objective neurological findings, or changes in the involved spinal level before and after each loading test., Conclusions: The lumbar extension-loading test is useful for assessment of lumbar spinal stenosis pathology and is capable of accurately determining the involved spinal level.

Background: Few studies have examined the prevalence of lumbar spinal stenosis (LSS) in the general population. The purposes of this study were to estimate the prevalence of LSS and to investigate correlated factors for LSS in Japan., Methods: A questionnaire survey was performed on 4,400 subjects selected from residents aged 40-79 years in Japan by stratified two-stage random sampling in 2010. The question items consisted of lower-limb symptoms suggestive of LSS, the diagnostic support tool for LSS (LSS-DST), demographic and lifestyle characteristics, comorbidities, the Japanese Perceived Stress Scale (JPSS), and the Mental Health Index 5 (MHI-5). Using the LSS-DST, the presence of LSS was predicted to estimate the prevalence of LSS. Logistic regression analysis was performed to examine the relationship between LSS and correlated factors., Results: Questionnaires were obtained from 2,666 subjects (60.6 %), consisting of 1,264 males (47.4 %). The mean (standard deviation) age was 60.0 (10.9) years. According to the LSS-DST, 153 subjects were regarded as having LSS. The prevalence was estimated to be 5.7 %. When standardizing this value with the age distribution of the Japanese population, it was estimated that 3,650,000 Japanese subjects aged 40-79 years might have LSS using the LSS-DST. Prevalence increased with age and was particularly high in subjects aged 70-79 years, irrespective of gender. As correlated factors, an advanced age (60 years or older), diabetes mellitus, urological disorders, and osteoarthritis/fracture as comorbidities, and depressive symptoms, were associated with LSS., Conclusions: This study elucidated the prevalence of LSS and factors associated with LSS in Japan. This is the first report describing the estimated prevalence of LSS and associated factors using a strictly sampled representative population.

Study Design: A cross-sectional multicenter observational study., Objective: To identify associations between lumbar spinal stenosis (LSS) and lifestyle-related diseases., Summary of Background Data: Impaired blood flow as a result of arteriosclerosis facilitates degenerative changes in the spine. However, associations between LSS and lifestyle-related diseases (hypertension, diabetes, and dyslipidemia) remain unclear., Methods: Participants comprised 526 patients diagnosed with LSS using the clinical diagnostic support tool and magnetic resonance imaging at 64 facilities. Data on 1218 males and 1636 females in the general population were selected from the 2006 National Health and Nutrition Survey as control data. We investigated the prevalence of lifestyle-related diseases (hypertension, diabetes, and dyslipidemia) and levels of hemoglobin A1c, total cholesterol, and high-density lipoprotein cholesterol. LSS and control groups were divided into 4 subgroups by age (nonelderly, <70 yr old; elderly, ≥ 70 yr) and sex. Statistical analyses were performed to compare patients with LSS and the control group using the χ test or Fisher exact text. Values of P < 0.05 were considered statistically significant., Results: Among nonelderly patients, proportions of patients with hypertension and diabetes mellitus were higher in patients with LSS than in controls (P < 0.01 each). The proportion of patients with hemoglobin A1c was 6.1% or greater and higher for female patients with LSS than for female controls (P < 0.05). No significant difference in the proportion of patients with dyslipidemia was apparent between the LSS and control groups., Conclusion: After adjusting for age and sex, this study revealed a close association between diabetes and hypertension in 50- to 69-year-old patients with LSS. Physicians should consider the possibility of concomitant hypertension or diabetes mellitus when examining 50- to 69-year-old patients with LSS.

Purpose: Limaprost, a prostaglandin E1 analog, has vasodilatory properties and increases blood flow of the nerve root. However, it has not been clarified whether limaprost affects pain sensation associated with radiculopathy due to lumbar spinal stenosis (LSS). The aim of this study was to compare the efficacy of oral limaprost with nonsteroidal anti-inflammatory drugs (NSAIDs) for radiculopathy., Methods: We performed a multicenter prospective randomized trial. Patients with LSS who had radicular-type neurologic intermittent claudication assessed based on a self-reported diagnostic support tool were randomized into three treatment groups. Limaprost, NSAIDs, or limaprost plus NSAIDs were administered orally for 6 weeks. Leg pain, low back pain (LBP) and the associated symptoms were assessed by a numerical rating scale (NRS) both at rest and on movement as well as the Roland-Morris Disability Questionnaire (RDQ) and Short Form (SF)-36., Results: Sixty-one patients were enrolled in the study. Each treatment finally reduced radicular pain, and the improvement was prominent in a combination treatment. There were no significant differences in radicular pain among three groups at final follow-up. LBP was not influenced by limaprost, and a significant reduction of LBP and RDQ was confirmed in a combination treatment compared with limaprost. Physical function of the SF-36 subscales after a combination treatment showed a marked alleviation compared with NSAIDs., Conclusions: These obtained findings suggest that the effects of limaprost seem to be limited to radicular pain, not for LBP. Overall, a combination treatment might be more effective in the management of radiculopathy induced by LSS than monotherapy with either agent.

Background: Intermittent claudication is a common symptom of both lumbar spinal stenosis (LSS) and peripheral arterial disease (PAD) in middle-aged and elderly people. However, the prevalence and clinical characteristics of LSS with PAD (LSSPAD) have not been investigated in a multicenter study. The aim of this study was to investigate the prevalence and clinical characteristics of LSS associated with PAD., Methods: 570 patients diagnosed with LSS using a clinical diagnostic support tool and MRI at 64 facilities were enrolled. We evaluated each patient's medical history, physical findings, ankle brachial index, Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score, and the Short Form 36 (SF-36) score. Statistical analyses were performed to compare LSSPAD patients and LSS patients without PAD using the t test, Mann-Whitney's U test, and multivariate recurrence analysis. p values of <0.05 were considered statistically significant., Results: The LSSPAD group comprised 38 patients (6.7 %); 20 (3.5 %) had pre-diagnosised PAD while 18 (3.2 %) had undetected PAD. The clinical characteristics of these patients were advanced age, diabetes, and a history of ischemic heart disease and cerebrovascular disorder. 570 patients enrolled, and 448 (78.6 %) of those patients were followed up at three months after enrollment. Pain in buttocks and legs improved less in the LSSPAD group than in the LSS group (p < 0.05). Improvements in the "general health" score in SF-36 were lower in the LSSPAD group than in the LSS group (p < 0.05)., Conclusions: Advanced age, diabetes, and a history of cerebrovascular disorder and ischemic heart disease were associated with LSSPAD. Because LSSPAD patients show less improvement in QOL than patients with LSS but without PAD do, clinicians should consider the coexistence of PAD in LSS patients.

Study Design: Descriptive experimental study., Objective: The aim of this study was to investigate the effect of exercise on cell proliferation in different areas of the intervertebral disc (IVD) and recruitment of cells possibly active in regeneration of normal rat lumbar IVDs., Summary of Background Data: Little is known about the effects of physical exercise on lumbar IVD tissue. Recently, stem cell niches in the perichondrium area of the IVD were identified and cells in these niches have been suggested to be involved in the normal regeneration of the IVD., Methods: Thirty Sprague-Dawley rats were exposed to 5-bromo-2-deoxyuridine (BrdU) diluted in the drinking water during 14 days. Fifteen rats ran on a treadmill daily for 50 min/d, 5 d/wk (exercise group), and 15 nonexercised rats served as controls. Immunohistochemical analyses (anti-BrdU antibody) were performed at 9, 14, 28, 56, and 105 days after the start of the exercise protocol. BrdU positive cells were counted in the stem cell niche area, the peripheral region of epiphyseal cartilage area, and the annulus fibrous outer and inner areas. Data were analyzed by 2-way analysis of variance (significance level; P < 0.05)., Results: The BrdU positive cell numbers in the stem cell niche and annulus fibrous outer regions were increased in discs from the exercising group on days 14 (P < 0.01) and 105 (P < 0.05) and at day 14 (P < 0.01) in the peripheral epiphyseal cartilage region compared with controls., Conclusion: Physical exercise was shown to have positive effects on cell proliferation in IVDs, with involvement of various disc regions, indicating a differential response by disc tissue to exercise depending on anatomical location and tissue characteristics.

Study Design: The effect of an EP1 receptor antagonist on pain-related behavior induced by nucleus pulposus (NP) applied to the dorsal root ganglion (DRG) in rats was investigated., Objective: We investigated pain-related behavior, the amount of prostaglandin E2 (PGE2), and neural damage to the DRG after application of NP to the DRG after administration of an EP1 receptor antagonist., Summary of Background Data: PGE2 induces mechanical allodynia and hyperalgesia, which are mediated by PGE2 receptors. EP1 is one of the PGE2 receptor subtypes. An EP1 antagonist reduces hyperalgesia, allodynia, and c-fos expression in the rat chronic nerve constriction model., Methods: Sprague-Dawley rats (n = 103) were used. Animals receiving NP were divided into three experimental groups (n = 12 in each group): saline, high-dose (5 mg/kg) EP1 receptor antagonist (RA), and low-dose (2.5 mg/kg) EP1-RA (orally once daily for 5 days). Animals in the sham group did not receive NP. Von Frey tests were used for pain-behavior testing. The amount of PGE2 in DRG and the number of activating transcription factor-3 (ATF3) immunoreactive positive cells were compared among groups., Results: The mechanical thresholds in the three groups decreased 7 days after surgery (just before treatment). The threshold in both the high- and low-dose EP1-RA groups increased at 11 days (5 days after treatment) and continued for 14 days. The thresholds in both the low- and high-dose EP1-RA groups increased significantly compared with the saline group (P < 0.05). The amount of PGE2 was significantly increased in the NP group compared with the sham and naïve animals after application of NP. ATF3 expression was increased by NP but was not increased after administration of the EP1-RA., Conclusion: An EP1 receptor antagonist improves pain-related behavior in the rat model and might be a potential agent to improve pain-related behavior in patients with lumbar disc herniation.

Study Design: The effects of exogenous 5-hydroxytryptamine (5-HT), tumor necrosis factor(TNF)-α, 5-HT + TNF in combination, and autologous nucleus pulposus (NP) at dorsal root ganglion (DRG) were examined using rat models., Objective: To examine the interaction of 5-HT with TNF for pain-related behavior in a rat lumbar disc herniation (LDH) model., Summary of Background Data: 5-HT and TNF have been shown to play roles in sciatica in lumbar disc herniation as chemical factors., Methods: Adult female Sprague-Dawley rats were divided into six groups: 5-HT group, TNF group, 5-HT + TNF (combination) group, NP group, control group, and naive group. Von Frey tests were used for pain-related behavior testing. Expressions of activating transcription factor 3 and calcitonin gene-related peptide (CGRP) were evaluated immunohistochemically. Expressions of TNF, TNF receptor 1 (TNFR1), and 5-HT2A receptors in the left L5 DRG were examined using western blotting. Plasma levels of 5-hydroxyindole acetic acid, a metabolite of 5-HT, were measured., Results: Mechanical withdrawal thresholds were significantly decreased in the 5-HT, TNF, combination, and NP groups compared with controls. Thresholds recovered after 14 days in the 5-HT and TNF groups, and after 28 days in the combination group. Exogenous 5-HT and TNF to the nerve root induced pain-related behavior and lasted for a shorter period compared with combination and NP groups. Activating transcription factor 3- and calcitonin gene-related peptide-immunoreactive DRG neurons were significantly increased only in the early phase in 5-HT, TNF, combination, and NP groups. TNF induced 5-HT2A receptor expressions in the DRG, while 5-HT induced TNF and TNF receptor 1 expressions., Conclusion: The present findings suggest that both 5-HT and TNF induce pain-related behavior and interact with each other to prolong pain-related behavior in a rat LDH model.

Study Design: An experimental rat study., Objective: To assess pain-related behavior and vascular endothelial growth factor (VEGF) expression induced by nucleus pulposus (NP) applied to nerve roots in rats., Summary of Background Data: Radiculopathy from disc herniation is caused by nerve compression and chemical inflammation. In experimental studies, a decrease in mechanical withdrawal threshold, blood flow, and nerve root dysfunction was reported when the NP was applied to nerve roots. However, neuron reproduction and changes in nerve root blood vessels have not been clearly understood., Methods: NP harvested from the tail was applied to the left L5 dorsal root ganglion (NP group; n = 77). As a control, sham-operated animals were used (n = 77). Behavioral testing with von Frey hairs was performed for 35 days. Immunoreactivity (IR) for VEGF, activating transcription factor-3, growth-associated protein-43 (GAP-43), factor VIII, and hypoxia-inducible factor-1[alpha] (HIF-1 a) were studied by immunohistochemistry. Western blot analyses of VEGF and GAP-43 were also performed., Results: The mechanical withdrawal threshold significantly decreased from 7 to 28 days in the NP group versus the sham group (P < 0.05). In the NP group, activating transcription factor-3-IR cells increased from 3 to 14 days (P < 0.05), hypoxia-inducible factor-1[alpha]-IR cells increased at 14 days (P < 0.05), and blood vessels with Factor VII-IR cells increased at 28 days (P < 0.05) compared with the sham group. The expression levels of VEGF and GAP-43 in the NP group significantly increased at 14 and 28 days (P < 0.05)., Conclusion: Neuron damage induced by NP applied to the nerve root at the early stage, and axon extension occurred from 14 days. VEGF increased at 14 and 28 days, and the numbers of blood vessels increased 28 days after surgery. The mechanical withdrawal threshold improved at 35 days. Regeneration and vascularization by VEGF might be associated with pain-related behavior.

Study Design: The association between intramuscular pressure and low back pain was investigated by measuring intramuscular pressure and blood flow, assessing histologic appearance, and performing immunohistochemical testing in rats., Objective: To develop an experimental rat model of increased intramuscular pressure (IMP) in the lumbar paraspinal muscles accompanied by reduced intramuscular blood flow (IMBF). The expression of neuropeptides in the dorsal root ganglion of the experimental model was also investigated., Summary of Background Data: Studies have reported that IMP in the lumbar paraspinal muscles is one of the causes of chronic low back pain. However, the pathology of low back pain accompanied by IMP has not been sufficiently clarified., Methods: A balloon was inflated below the vertebral fascia of rats (balloon group) and intramuscular pressure and blood flow in the lumbar paraspinal muscles were measured. Intramuscular pressure was measured using a pressure transducer, whereas IMBF was measured using a contact-type laser Doppler flowmeter. Compared with the sham operation group, intramuscular pressure was higher and IMBF was lower for the balloon group at 1 hour and 1 day after insertion. In addition, at 1 hour and 1 day after insertion, IMBF and pressure were continuously measured while rats were positioned in flexion for 1 hour., Results: Intramuscular pressure was significantly higher and IMBF was significantly lower in the balloon group at 1 day after insertion (P < 0.05). Expression of substance P, a neuropeptide, was also observed in the dorsal root ganglion of the first lumbar vertebra., Conclusion: These findings suggest that IMP and decreased IMBF in the lumbar paraspinal muscles induce inflammation and pain in the lower back.

Study Design: Cerebral activation by lumbar mechanical stimulus was investigated by functional magnetic resonance imaging in healthy subjects and patients with chronic low back pain (LBP)., Objectives: To characterize the cerebral substrates of LBP, and to explore a possible pathologic pattern of cerebral activation in chronic LBP patients., Summary of Background Data: The cerebral substrates of LBP have been poorly defined in contrast to those of cutaneous somatic pain., Methods: Eight healthy volunteers and 6 patients with idiopathic, chronic LBP were recruited. Each subject was placed in the prone position on a 3 Tesla MRI scanner, and stimulated by manual pressure with the tail of an air-filled, 20-mL syringe at 5 cm left of the fourth-fifth lumbar spinal interspace. Three blocks of 30-second painful stimulus, calibrated at either 3 or 5 on the 10-cm visual analog scale (VAS), were applied with intervening 30-second rest conditions during whole-brain echo-planar imaging. VAS of pain intensity and unpleasantness were evaluated after each session. Functional imaging was analyzed using a multisubject general linear model with Bonferroni multiple comparisons at P < 0.05., Results: Pain thresholds were smaller (P < 0.05) and VAS of unpleasantness was larger in LBP patients than in healthy subjects. Activation was observed at the prefrontal, insular, posterior cingulate cortices (PCC), supplementary motor, and premotor areas predominantly in the right hemisphere, but not at the somatosensory cortices. LBP patients showed augmented activation compared with healthy volunteers specifically at the right insula, supplementary motor, and PCC., Conclusion: Chronic LBP patients showed increased tenderness at the lower back, higher aversive reaction to pain, and augmented LBP-related cerebral activation. The LBP-related activation is characterized by the absence of sensory-discriminative component and the involvement of PCC.

Study Design: The role of 5-hydroxytryptamine (5-HT) in sciatica in lumbar disc herniation (LDH) in rats was investigated., Objective: We evaluated the effects of exogenous 5-HT applied on the nerve root on pain-related behavior, the release of endogenous 5-HT in plasma, and the expression of 5-HT2A receptors in dorsal root ganglion (DRG) in a rat LDH model., Summary of Background Data: In previous studies, 5-HT2A receptor antagonists improved sciatica in patients with LDH and attenuated pain-related behavior induced by nucleus pulposus applied to the nerve root in rats., Methods: Adult female Sprague-Dawley rats were divided into four experimental groups [control group; low-dose (10 microg) 5-HT-group; high-dose (30 microg) 5-HT-group; and autologous nucleus pulposus (NP) and saline group] and each drug was applied to the L5 nerve root. Von Frey tests were used for pain-behavior testing. To assess levels of endogenous 5-HT released in capillaries surrounding inflamed nerve roots, we measured 5-hydroxyindole acetic acid (5-HIAA), a metabolite of 5-HT. Expression of 5-HT2A receptors in the left L5 DRG was examined by immunohistochemical and immunoblotting analyses in the control and NP groups., Results: Mechanical withdrawal thresholds of the high-dose 5-HT and the NP groups were significantly decreased after surgery compared with the control group and recovered after 14 days in the high-dose 5-HT group. 5-HIAA in plasma was increased by nucleus pulposus applied on the nerve root for 7 days after surgery. The expression of 5-HT2A receptors was enhanced in a time-dependent manner by nucleus pulposus., Conclusion: Exogenous 5-HT to the nerve root induced pain-related behavior with short-lasting effects compared with the nucleus pulposus application. 5-HIAA content in plasma and expression of 5-HT2A receptors in DRG neurons increased early time points after the nucleus pulposus application. These results suggest that 5-HT plays a role in the early phase of the chemical pathogenesis of sciatica in LDH in rats.

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-HT(2A) 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-HT(2A) 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 naive 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 naive 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.

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 > or = 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 > or = 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.

Background: Lumbar facet joint tissue has inflammatory cytokines. However, no reports have shown whether inflammatory cytokines in the facet joint leads to pain. This study was designed to characterize the correlation between inflammatory cytokines released from facet joint tissue and symptoms in degenerative lumbar spinal disorders. The purpose of this study was to seek involvement of inflammatory facet joint for radiculopathy in lumbar spinal canal stenosis with clinical and anatomical studies., Methods: Lumbar facet joint cartilage and synovial tissues in 40 cases of posterior lumbar surgery were harvested to measure tumor necrotizing factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) during operation. The visual analogue scale (VAS) and Roland-Morris disability questionnaire (RDQ) were used to examine the correlation between cytokine concentration and symptoms. Coloring agent was injected into facet joints of fresh cadavers to find leakage of pigment from the facet joint into the spinal canal., Results: Inflammatory cytokines were detected in the joint tissues in the lumbar spinal canal stenosis (LSCS) and lumbar disc herniation (LDH) groups. A positive reaction rate of IL-1beta was significantly higher in the LSCS group than in the LDH group. IL-1beta-positive cases in the LSCS group showed higher VAS scores for leg pain and higher RDQ scores. Intraspinal canal tissues including lumbar nerve root were stained by injection of methylene blue into the facet joints., Conclusions: IL-1beta in facet joint cartilage in LSCS was associated with leg pain and a decline of quality of life. Inflammatory cytokines produced in degenerated facet joint may leak into the intraspinal space through the lateral part of the ventral facet joint capsule. These results suggest the involvement of inflammatory cytokines in degenerated lumbar facet joints regarding the genesis of pain production.

Background: Since 1996, we have applied endoscopic techniques to the treatment of various spinal disorders. The purpose of this study was to clarify the complications of endoscopic spinal surgery using thoracoscopy and retroperitoneoscopy., Methods: Fifty-two patients (26 male patients, 26 female patients, mean age: 49.7 years) underwent endoscopic surgery for various spinal disorders including burst fracture (20 cases), pyogenic spondylitis (10 cases), tumor (8 cases), scoliosis (4 cases), thoracic disc herniation (3 cases), and others. Thoracoscopy was performed in 20 patients, retroperitoneoscopy in 20 patients, and a combination of thoracoscopy and retroperitoneoscopy in 12 patients. Intraoperative and postoperative complications were retrospectively examined for these cases., Results: The intraoperative complications for thoracoscopic surgery were two cases of extensive bleeding (more than 2500 ml); for retroperitoneoscopic surgery, there were three cases of extensive bleeding and one case of penetration of the peritoneum; and for the combination of thoracoscopy and retroperitoneoscopy, there were two cases of extensive bleeding. The postoperative complications for thoracoscopic surgery were three cases of atelectasis and other respiratory complications; for retroperitoneoscopic surgery, the most common complication was transient neurological dysfunction (five cases); and for the combination of thoracoscopy and retroperitoneoscopy, three cases of atelectasis were observed. The overall incidence of complications in endoscopic spinal surgery was 42.3% (20/52 cases). Of the intraoperative complications, extensive bleeding was most frequent, and of postoperative complications, respiratory problems and transient neural damage were most frequent. The incidences of extensive bleeding and respiratory problems during the past 4 years were significantly fewer than during the first 4 years of surgical experience. Intraoperative bleeding and the operative time were significantly decreased after the first five cases of burst fracture., Conclusions: Complications of endoscopic spinal procedures occurred in 42.3% of our cases, but decreased with increase in surgical experience.

Three elements contribute to the neurologic symptoms of the lumbar spine or its multiplicity from an anatomical viewpoint. The first element is the problem of neural tissue. The second element is the bone or the soft tissue existing around the circumference of the neural tissue. The third element is the correlation of the above two. In other words, the neural tissue as content is too large or the adjacent tissue as container is too narrow or else an aberration in the correlation of the aforesaid is involved. Therefore, it is necessary to study those three elements to comprehend the neurologic symptoms of the lumbar spine.

Background: The North American Spine Society states that lumbar spinal stenosis (LSS) is a clinical syndrome, and there is insufficient evidence to make a recommendation for or against a correlation between clinical symptoms or function and the presence of anatomic narrowing of the spinal canal on MRI. The main purpose of this study was to assess the influence of the magnitude of dural tube compression on MRI on LSS symptoms at the cross-sectional and 1-year follow-up. Methods: This was a prospective cohort study of 459 participants who were assessed for LSS using a questionnaire and conventional MRI of the lumbar spine. After 1 year, 335 subjects (follow-up rate 73.0%) were assessed for LSS using the same questionnaire. The time course of the clinical subjective symptoms of LSS and the relationship between the said symptoms of LSS and magnitude of dural tube compression on MRI were analyzed in a cross-sectional and longitudinal fashion. Results: 1) The dural sac cross-sectional area (DCSA) decreased with age. 2) Severe dural tube compression had a strong influence on the presence of symptomatic LSS; however, 40%–70% of participants with severe dural tube compression did not show clinical symptoms of LSS. 3) At the 1-year follow-up, >50% of the LSS-positive participants in the initial year were reclassified as LSS negative, and 10% of the LSS-negative participants were reclassified as LSS positive. 4) The magnitude of the DCSA on MRI did not directly affect the presence of LSS at the 1-year follow-up. Conclusion: LSS symptoms were changeable. Anatomical dural tube compression on MRI did not predict the presence of clinical LSS symptoms at the 1-year follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Neuropathic pain, commonly related to intervertebral disk (IVD) degeneration, responds poorly to standard pain treatments. Serotonin-noradrenaline reuptake inhibitors (SNRIs) have been reported to reduce neuropathic pain; however their effect on radiculopathy induced by lumbar disk herniation remains unclear. The aim of this study was to investigate the effect of SNRI duloxetine in rat model of IVD-related neuropathic pain.Materials and Methods: Effects of SNRI duloxetine were tested in Sprague-Dawley rats (n = 135). Neuropathic pain was induced by applying autologous nucleus pulposus (NP) on the left L5 dorsal root ganglion (DRG). Duloxetine in concentrations 0.4 mg/kg (low dose) and 1.2 mg/kg (high dose) or saline were administered orally for 10 days. Von Frey test was carried out on post-operative days 2, 7, 14, 21, and 28 to test pain sensitivity. Immunohistochemistry of L5 DRG and L5 segment of spinal cord (SC) was performed on days 7 and 21 to examine expressions of tumor necrosis factor alpha (TNF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ionized calcium-binding adapter molecule 1 (Iba1). On days 14, 21, and 28, expressions of TNF in DRG as well as NGF and BDNF in SC were tested by immunoblotting. Sham-operated rats and naive rats were used as controls.Results: Duloxetine in both concentrations significantly improved pain threshold from postoperative day 21 onward, compared to the NP + saline group (p < 0.05). High-dose duloxetine significantly inhibited the expression of TNF in DRG (day 28, p < 0.05). Both duloxetine concentrations reduced the expression of NGF in SC (day 21, p < 0.05), but the expression of BDNF remained unchanged.Conclusion: SNRI duloxetine inhibited neuropathic pain in rats possibly via down-regulating TNF, NGF, and microglia activation. We conclude that duloxetine, and most likely other SNRIs, may be used for the management of lumbar neuropathic pain. [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]

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]

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]

Background: There are no diagnostic support tools composed of a simple, single-sheet, self-administered, self-reported history questionnaire (SSHQ) for patients with leg symptoms caused by either lumbar spinal stenosis (LSS) or lumbar disc herniation (LDH), at the same time, can discriminate the two diseases.Methods: We conducted retrospective and prospective derivation studies and a prospective validation study. Based on data from 137 patients with LSS and 206 with LDH, we identified key prediction factors to establish the diagnosis of LSS and LDH, which became the basis of a temporary SSHQ. Next, we performed a prospective derivation study in which 296 patients with LSS or LDH completed preoperatively this temporary SSHQ. After univariate and multivariate analyses of each question, questions on both diseases in addition to age factor were selected, providing the final version of the SSHQ. A validation study was subsequently performed with 342 consecutive patients with leg symptoms. The sensitivity, specificity and likelihood ratio of this SSHQ were calculated to determine the cut-off points for LSS and LDH.Results: A SSHQ with 15 questions was developed from retrospective and prospective derivation studies. The score of each question was weighted based on the multivariate analysis and then, it was approximated to integer value. According to assessment of the discriminatory performance of the clinical prediction rule of the SSHQ, the cut-off point for LSS was ≥13 and that for LDH was ≥11. The sensitivity, specificity, and positive and negative likelihood ratios of this SSHQ at those cut-off points were, respectively, 92.7%, 84.7%, 6.07, and 0.09 for LSS, and 91.0%, 85.2%, 6.15, and 0.11 for LDH.Conclusions: This is the first report of a diagnostic support tool for patients with LSS- or LDH-induced leg symptoms combined in a single SSHQ that could help establish diagnosis of the two diseases in the daily clinical practice. [ABSTRACT FROM AUTHOR]

Background: There is little evidence regarding long-term outcomes of locomotor dysfunction such as cardiovascular events, quality of life, and death. We are conducting a prospective cohort study to evaluate risk of cardiovascular disease, quality of life, medical costs, and mortality attributable to locomotor dysfunction. The present study determined baseline characteristics of participants in the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS). Methods: Cohort participants were recruited from residents between 40 and 80 years old who received regular health check-ups conducted by local government each year between 2008 and 2010 in Minami-Aizu Town and Tadami Town in Fukushima Prefecture, Japan. Musculoskeletal examination included assessment of physical examination of the cervical and lumbar spine, and upper and lower extremities and of physical function, such as grasping power, one-leg standing time, and time for the 3-m timed up-and-go test. Cardiovascular risk factors, including blood pressure and biological parameters, were measured at annual health check-ups. We also conducted a self-administered questionnaire survey. Results: LOHAS participants comprised 1,289 men (mean age 65.7 years) and 1,954 women (mean age 66.2 years) at the first year. The proportion of obese individuals (body mass index 25.0 kg/m) was 31.9% in men and 34.3% in women, and 41.0% of participants reported being followed up for hypertension, 7.0% for diabetes, and 43.6% for hypercholesterolemia. Prevalence of lumbar spinal stenosis was 10.7% in men and 12.9% in women, while prevalence of low back pain was 15.8% in men and 17.6% in women. Conclusion: The LOHAS is a novel population-based prospective cohort study that will provide an opportunity to estimate the risk of cardiovascular disease, quality of life, medical costs, and mortality attributable to locomotor dysfunction, and to provide the epidemiological information required to develop policies for detection of locomotor dysfunction. [ABSTRACT FROM AUTHOR]