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Background: Age-related differences in the limited range of motion of the lower extremities and their relationship with low back pain in juvenile athletes have not been well assessed. This study investigated the relationship between low back pain and limited range of motion of the hip and knee in young baseball players during the baseball season. Results: Participants comprised 1215 baseball players (216 pitchers, 999 fielders) aged 6–16 years who underwent medical checkups (self-completed questionnaire and physical examination). Of the 1215 players, 255 (21.0%) experienced seasonal low back pain requiring rest during the previous year. The prevalence of low back pain and a positive Thomas test, straight-leg-raising test, and heel-to-buttock test increased with age. Univariate analysis revealed that a positive heel-to-buttock test in both the throwing and non-throwing arm sides in the 11–12 age group and a positive Thomas test in the throwing arm side in the 13–14 age group were associated with seasonal low back pain (P = 0.0051, P = 0.021, and P = 0.048, respectively). Multivariate analysis, adjusted for factors associated with low back pain, showed significant associations between the positive heel-to-buttock test (odds ratio 1.75, 95% confidence interval 1.11–2.79; P = 0.016) and low back pain in players aged 11–14 years. Conclusions: A positive heel-to-buttock test is potentially associated with low back pain among juvenile baseball players. Particular attention should be paid to the limited range of motion of the knee joint and tightness of the quadriceps femoris muscle among baseball players with low back pain aged 11–14 years. [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]

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]

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]

Introduction: The reconstruction of bone defects of open lower leg fractures is challenging, and there is no established treatment strategy to date, especially in the acute phase. We report herein an 'acute Masquelet technique' for reconstructing bone defects of open lower limb fractures as the primary treatment in the acute phase. Patients and Methods: We retrospectively analyzed the outcomes of seven lower limbs of the seven Japanese patients (five males, two females, aged 24–76 years [mean 53 years]) who underwent the acute Masquelet technique for open fractures with bone defects. We evaluated postsurgical complications including deep infection, absorption of grafted bone, and the final result of the bone union. Results: Deep infection occurred in one of the seven limbs (14%). There was no case with absorption of grafted bone in our series. We have treated two patients who needed additional surgery for delayed bone union. Bone union was eventually obtained in all seven limbs. All of the patients became pain-free and could walk without a cane. Conclusion: The 'acute Masquelet technique' was quite useful for reconstructing bone defects of open lower limb fractures as the primary treatment in the acute phase. We believe that this is one of the options that might be successful in the treatment of open lower limb fractures. [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]

Background: There are some previous reports of gait analysis using a rodent pain model. Applying the CatWalk method, objective measurements of pain-related behavior could be evaluated, but this method has not been investigated using the nucleus pulposus (NP) applied model, which was developed as a model of lumber disc herniation. We aimed to measure mechanical withdrawal thresholds and analyze gait patterns using the CatWalk method for the evaluation of the pain-related behavior caused by NP application. Methods: Twenty-four nine-week-old female Sprague-Dawley rats were randomly divided into two experimental groups, the NP group ( n = 12), in which autologous NP from the tail was applied to the left L5 dorsal root ganglion, and the sham-operated group ( n = 12). Measurements of mechanical withdrawal thresholds were performed using von Frey filaments touching the left footpads, and gait analysis was performed using the CatWalk method. These experiments were conducted 1 day before surgery and 7, 14, 21, and 28 days after surgery. Data were statistically analyzed using the Wilcoxon rank-sum test. Results: The NP group showed significantly lower withdrawal thresholds than the sham group at days 14 and 21. Stand (duration of contact of a paw with the glass plate) was significantly higher in the NP group at days 7 and 14, whereas step cycle (duration between two consecutive initial contacts of the same paw) and duty cycle ( stand as a percentage of step cycle) were the same at day 7. Long initial dual stance (duration of ground contact for both hind paws simultaneously, but the first one in a step cycle of a target hind paw) of the right hind paw was measured at days 7 and 14. The left hind paw per right hind paw ratio of the stand index (speed at which the paw loses contact with the glass plate) and mean intensity (mean intensity of the complete paw) changed at day 7 or 14. Phase dispersion (parameter describing the temporal relationship between placement of two paws) of the hind paws decreased at day 7. Conclusions: Rats with applied NP showed a decreased withdrawal threshold and abnormal gait. The differences in gait parameters between the NP and sham groups were observed at an earlier time point than the withdrawal thresholds. Gait analysis could be an effective method for understanding pain caused by applied NP. [ABSTRACT FROM AUTHOR]

Purpose: A considerable portion of chronic low back pain (cLBP) patients lack anatomical abnormality, resist conventional therapeutic interventions, and their symptoms are often complicated with psychological and social factors. Such patients have been reported to show cerebral abnormalities both in anatomy and function by neuroimaging studies. Here we examined differences in cerebral reactivity to a simulated low back pain stimulus between cLBP patients and healthy controls by functional magnetic resonance imaging (fMRI), and their behavioral correlates from a psychophysical questionnaire. Methods: Eleven cLBP patients and 13 healthy subjects (HS) were enrolled in this study. After psychophysical evaluation on-going pain with McGill Pain Questionnaire Short Form (MPQ), they underwent whole-brain fMRI in a 3-Tesla MRI scanner while receiving three blocks of 30-s mechanical pain stimuli at the left low back with a 30-s rest in between, followed by a three-dimensional anatomical imaging. Functional images were analyzed with a multi-subject general linear model for blood oxygenation level-dependent (BOLD) signal changes associated with pain. Individual BOLD signal amplitudes at activated clusters were examined for correlation with psychophysical variables. Two in the cLBP and five data sets in the HS groups were excluded from analysis because of deficient or artifactual data or mismatch in age. Results: The HS group showed LBP-related activation at the right insular cortex, right dorsolateral prefrontal cortex (DLPFC), left anterior cingulate cortex (ACC), and left precuneus; and deactivation in a large area over the parietal and occipital cortices, including the bilateral superior parietal cortex. On the other hand, the cLBP group did not show any significant activation at those cortical areas, but showed similar deactivation at the bilateral superior parietal cortex and part of the premotor area. An HS > cLBP contrast revealed significantly less activity at the ACC and DLPFC in the cLBP group, which was negatively correlated with higher MPQ scores. Conclusions: The cLBP patients showed attenuated reactivity to pain at the ACC and DLPFC, known cortical areas mediating affective component, and top-down modulation, of pain. The present results might be associated with possible dysfunction of the descending pain inhibitory system in patients with chronic low back pain, which might possibly play a role in chronification of pain. [ABSTRACT FROM AUTHOR]

The post-operative patellar tendon length was studied to evaluate the possible tendon length change after anterior cruciate ligament (ACL) reconstruction with hamstring autografts. The Insall-Salvati index, modified Insall-Salvati index, curved modified Insall-Salvati index and Caton-Deschamps index were observed by MRI during a follow-up period of 12 weeks on 20 ACL reconstructed knees. The results showed no patellar baja or alta pre-existed on those ACL injured patients. After a follow-up period of 12 weeks, no patellar tendon length change was observed. It is suggested that the change of patella was not the primary reason that may contribute to the premature patellofemoral joint osteoarthritis after ACL reconstruction. [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]

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. [ABSTRACT FROM AUTHOR]

Purpose: Although inflammatory processes play an essential role in painful intervertebral disc (IVD) degeneration, the underlying regulatory mechanisms are not well understood. This study was designed to investigate the expression, regulation and importance of specific toll-like receptors (TLRs)-which have been shown to play an essential role e.g. in osteoarthritis-during degenerative disc disease. Methods: The expression of TLRs in human IVDs was measured in isolated cells as well as in normal or degenerated IVD tissue. The role of IL-1β or TNF-α in regulating TLRs (expression/activation) as well as in regulating activity of down-stream pathways (NF-κB) and expression of inflammation-related genes (IL-6, IL-8, HSP60, HSP70, HMGB1) was analyzed. Results: Expression of TLR1/2/3/4/5/6/9/10 was detected in isolated human IVD cells, with TLR1/2/4/6 being dependent on the degree of IVD degeneration. Stimulation with IL-1β or TNF-α moderately increased TLR1/TLR4 mRNA expression (TNF-α only), and strongly increased TLR2 mRNA expression (IL-1β/TNF-α), with the latter being confirmed on the protein level. Stimulation with IL-1β, TNF-α or Pam3CSK4 (a TLR2-ligand) stimulated IL-6 and IL-8, which was inhibited by a TLR2 neutralizing antibody for Pam3CSK4; IL-1β and TNF-α caused NF-κB activation. HSP60, HSP70 and HMGB1 did not increase IL-6 or IL-8 and were not regulated by IL-1β/TNF-α. Conclusion: We provide evidence that several TLRs are expressed in human IVD cells, with TLR2 possibly playing the most crucial role. As TLRs mediate catabolic and inflammatory processes, increased levels of TLRs may lead to aggravated disc degeneration, chronic inflammation and pain development. Especially with the identification of more endogenous TLR ligands, targeting these receptors may hold therapeutic promise. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to anatomically investigate the proximal origin of flexor-pronator muscles (FPMs) and clarify their contribution to dynamic stabilization of the elbow joint during valgus stress. Methods: 52 elbows from 26 donated formalin-fixed cadavers were examined. The pronator teres muscle (PT), flexor carpi radialis muscle (FCR), palmaris longus muscle (PL), flexor digitorum superficialis muscle (FDS), and flexor carpi ulnaris muscle (FCU) were identified, and their proximal origin and relationship to the anterior bundle of the medial ulna collateral ligament (AOL) were macroscopically and histologically investigated. Results: The PT, FCR, PL, and FDS converged and formed a common tendon at their proximal origin (the anterior common tendon: ACT). The ACT was attached to the medial epicondyle and the joint capsule, just anterior and parallel to the AOL. The histological morphology of the ACT was quite similar to that of the AOL. The ulnar head of the PT was observed in 48 of 52 elbows (92.3 %), just behind the humeral head of PT. It mainly originated from the anterior edge of the sublime tubercle, while the upper part of ulnar head transitioned directly into the thickened joint capsule just anterior to the AOL. Conclusion: The proximal attachment of the FPMs had a characteristic morphology. According to our results, the ACT and PT might assist the AOL by sharing static and dynamic traction forces applied to the medial elbow joint. [ABSTRACT FROM AUTHOR]

Purpose: Limaprost, a prostaglandin E 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. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain has an impact on psychological and social factors. It is known that stress influences physiological and behavioral changes and affects several neurotransmitter and hormonal systems. It is also known that corticosterone is increased by stress. The role of chronic stress in sciatica in lumbar disc herniation (LDH) in rats has not been investigated. The aim of this study was to investigate the effect of the restraint stress (RS) on pain-related behavior induced by application of nucleus pulposus (NP) in rats.Materials and Methods: Adult female Sprague-Dawley rats were divided into six experimental groups (naive group; naive + RS; sham group; sham + RS; autologous nucleus pulposus [NP] applied on the left L5 nerve root [NP group]; and NP + RS group). Von Frey tests were used to test pain-related behavior. Concentrations of plasma corticosterone were measured to assess changes in levels of endogenous corticosterone caused by RS. Expression of ATF-3 in the left L5 DRG was examined by immunohistochemical analyses in each group.Results: Mechanical withdrawal thresholds of the NP and NP + RS groups were significantly decreased after surgery compared with the naive group. Although the thresholds in the NP group recovered after 28 days, the thresholds in the NP + RS group were significantly decreased during the 42 days after surgery. RS increased the concentration of plasma corticosterone at 21 and 42 days after surgery. In the NP and the NP + RS groups, the expression of ATF-3 was significantly increased at 7 days after surgery. The expression of ATF-3 was sustained for 21 days by RS.Conclusion: Concentrations of plasma corticosterone were increased in three groups that underwent RS. The pain-related behavior persisted for the long term in the LDH model. The expression of ATF-3 in DRG neurons increased for 21 days by RS. These results suggest that RS plays a role in the chronicity of pain-related behavior in the LDH rats. [ABSTRACT FROM AUTHOR]

Purpose: TNFα is an inflammatory mediator related to neuropathic pain including sciatica. Much basic research suggests that anti-TNFα therapy may be useful for the treatment of sciatica. The purpose of this study was to clarify the effects of etanercept in a dorsal root ganglion (DRG) compression model.Methods: Adult male Sprague-Dawley rats (200-250 g, n = 60) were used. An L-shaped stainless rod was used to compress the left L5 DRG in the saline and etanercept groups. No rod was used in the sham group. In the etanercept group, 1 mg of etanercept was applied locally onto the DRG at the end of surgery. Saline was applied in the saline and sham groups. On day 3 and day 7 after surgery, the number of ED1-immunoreactive (IR) cells (macrophages) in the DRG was calculated by immunohistochemical methods (n = 6). In addition, double-immunofluorescence labeling for ED1 and TNFα was performed. Behavioral testing with von Frey filaments and a heat stimulator was performed (n = 12).Results: ED1-IR cells in the DRG significantly increased in the control group compared with the sham group (p < 0.05). Some ED1-IR cells were co-labeled for TNFα. In the etanercept group, decrease in mechanical threshold was significantly inhibited compared with the saline group (p < 0.05). Thermal hyperalgesia was observed in the control group, but in neither the sham nor etanercept group (p < 0.05).Conclusion: Etanercept attenuated the pain-related behavior induced by DRG compression. These findings suggest that mechanical effects on the DRG might be reduced by etanercept in addition to the effects on nucleus pulposus in lumbar disc herniation. [ABSTRACT FROM AUTHOR]

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]

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]

Inadvertently, the Fig. 7 was published incorrectly in the original publication of the article. The correct figure should be as below: [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]