Search

Introduction: Platelet-rich plasma obtained by centrifuging peripheral blood can promote osteogenesis owing to its abundant growth factors but has drawbacks, including rapid growth factor loss and inconsistent effects depending on donor factors. To overcome these issues, we were the first in the world to use freeze-dried human induced pluripotent stem cell-derived megakaryocytes and platelets (S-FD-iMPs) and found that they have osteogenesis-promoting effects. Since turbulence was found to activate platelet biogenesis and iPS cell-derived platelets can now be produced on a clinical scale by a device called VerMES, this study examined the osteogenesis-promoting effect and safety of clinical-scale FD-iMP (V-FD-iMPs) for future human clinical application. Method: We administered either S-FD-iMPs, V-FD-iMPs, or saline along with artificial bone to the lumbar spine of 8-week-old male Sprague–Dawley rats (n = 4 each) and evaluated bone formation by computed tomography (CT) and pathology. Next, we administered V-FD-iMPs or saline along with artificial bone to the lumber spines of 5-week-old male New Zealand White rabbits (n = 4 each) and evaluated the bone formation by CT and pathology. Rats (n = 10) and rabbits (n = 6) that received artificial bone and V-FD-iMPs in the lumbar spine were also observed for 6 months for adverse events, including infection, tumor formation, and death. Results: Both V-FD-iMPs and S-FD-iMPs significantly enhanced osteogenesis in the lumber spines of rats in comparison with the controls 8 weeks postoperatively, with no significant differences between them. Furthermore, V-FD-iMPs vigorously promoted osteogenesis in the lumber spines of rabbits 8 weeks postoperatively. In rats and rabbits, V-FD-iMPs showed no adverse effects, including infection, tumor formation, and death, over 6 months. Conclusion: These results suggest that V-FD-iMPs promote safe osteogenesis.

Abstract Background This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models. Methods Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated. Results The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase (Dnmt 3a), ten–eleven translocation (Tet) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups. Conclusions The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered.

Introduction: Low-back pain causes sleep disorders, which impairs the quality of life (QOL) of patients. Sleep disorders are associated with lumbar spinal stenosis (LSS); however, the postoperative effects of LSS surgery on sleep disorders are unknown. This study aimed to assess sleep disorders in patients with LSS using wearable activity trackers and determine whether surgery improves sleep quality. Methods: A total of 39 patients scheduled for LSS surgery (mean age 71.1±8.7 years; 22 men and 17 women) were studied. Sleep disorders in the participants were objectively evaluated using a wearable Motionlogger Micro system. Sleep efficiency (SEf), mean active count (MAC), and wake after sleep onset (WASO) were measured before and 6 months following surgery. Furthermore, the patient-based outcomes of pain and QOL-related scores were measured and compared with those of healthy participants. The group with improved SEf following surgery was designated as “nonpoor sleepers,” whereas the group that did not exhibit improvements was designated as “poor sleepers.” The two groups were compared based on patient factors, patient-based questionnaires, and sleep disorder measurements. Results: The SEf and WASO were significantly worse in patients with LSS compared with healthy participants (P

Abstract Platelet-rich plasma (PRP) promotes bone union through osteoinduction. We investigated whether adding demineralized bone matrix (DBM), derived naturally from biomaterial and with various growth factors, for osteoconductivity and bone marrow fluid for osteogenesis results in different bone unions. Eight-week-old male Sprague–Dawley rats were divided into four groups of five based on transplantation material: sham control (C group); DBM alone (D group); DBM + PRP (DP group); and DBM + PRP + bone marrow fluid (DPB group). After posterolateral fusion at L3-5, postoperative weekly CT imaging determined average number of bone union in facet joints (4 joints × 5 animals = 20 joints) and bone formation. Pathological evaluation and bone strength were assessed using 3-point bending two weeks postoperatively. Facet joint bone union at four weeks postoperatively was 4/20 (20%, DP group) and 8/20 (40%, DPB group) joints. Six weeks postoperatively, it was 7/20 (35%, D group), 12/20 (60%, DP group), and 16/20 (80%, DPB group). Eight weeks postoperatively, it was 13/20 (65%, D group), 17/20 (85%, DP group), and 20/20 (100%, DPB group), suggesting that DPB > DP > D > C. Bone formation and bone strength showed a similar DPB > DP > D > C group trend. Adding PRP and bone marrow fluid to DBM promotes bone union and strength.

Abstract Background Diclofenac etalhyaluronate (DF-HA) is a recently developed analgesic conjugate of diclofenac and hyaluronic acid that has analgesic and anti-inflammatory effects on acute arthritis. In this study, we investigated its analgesic effect on osteoarthritis, using a rat model of monoiodoacetate (MIA). Methods We injected MIA into the right knees of eight 6-weeks-old male Sprague–Dawley rats. Four weeks later, rats were randomly injected with DF-HA or vehicle into the right knee. Seven weeks after the MIA injection, fluorogold (FG) and sterile saline were injected into the right knees of all the rats. We assessed hyperalgesia with weekly von Frey tests for 8 weeks after MIA administration. We took the right knee computed tomography (CT) as radiographical evaluation every 2 weeks. All rats were sacrificed 8 weeks after administration of MIA for histological evaluation of the right knee and immunohistochemical evaluation of the DRG and spinal cord. We also evaluated the number of FG-labeled calcitonin gene-related peptide (CGRP)-immunoreactive(ir) neurons in the dorsal root ganglion (DRG) and ionized calcium-binding adapter molecule 1 (Iba1)-ir microglia in the spinal cord. Results Administration of DF-HA significantly improved pain sensitivity and reduced CGRP and Iba1 expression in the DRG and spinal cord, respectively. However, computed tomography and histological evaluation of the right knee showed similar levels of joint deformity, despite DF-HA administration. Conclusion DF-HA exerted analgesic effects on osteoarthritic pain, but did not affect joint deformity.

Study Design Prospective cohort study (open-label, single-arm, and non-blinded). Purpose This study aims to determine the effects of systemic administration of tocilizumab, an anti-interleukin-6 (IL-6) receptor antibody on refractory low back pain and leg symptoms. Overview of Literature IL-6 overexpression is associated with neuropathic pain pathogenesis, which is potentially followed by chronic low back pain, including leg pain and numbness. This finding suggest that inhibition of IL-6 at the site of pain or in the transmission pathway could provide novel therapeutic targets for chronic low back pain. Methods This prospective, single-arm study included 11 patients (eight men; mean age, 62.7 years) with ≥3-months’ chronic pain history due to lumbar disease. Subcutaneous TCZ injections were administered twice, at a 2-week interval. We evaluated low back pain, leg pain, and leg numbness using numeric rating scales and the Oswestry Disability Index (ODI; baseline and 6 months postinjection); serum IL-6 and tumor necrosis factor-α levels (baseline and 1 month postinjection); and clinical adverse events. Results Intractable symptoms reduced after TCZ administration. Low back pain improved for 6 months. Improvements in leg pain and numbness peaked at 4 and 1 month, respectively. Improvements in ODI were significant at 1 month and peaked at 4 months. Serum IL-6 was increased at 1 month. IL-6 responders (i.e., patients with IL-6 increases >10 pg/mL) showed particularly significant improvements in leg pain at 2 weeks, 1 month, and 2 months compared with nonresponders. We observed no apparent adverse events. Conclusions Systemic TCZ administration improved symptoms effectively for 6 months, with peak improvements at 1–4 months and no adverse events. Changing serum IL-6 levels correlated with leg pain improvements; further studies are warranted to elucidate the mechanistic connections between lumbar disorders and inflammatory cytokines.

Abstract This study aimed to perform a comparative analysis of postoperative results between lumbar degenerative spondylolisthesis (LDS) treated with oblique lateral interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) from the Chiba spine surgery registry database. Sixty-five patients who underwent single-level OLIF (O group) for LDS with ≥ 3 years’ follow-up were retrospectively reviewed. The control group comprised 78 patients who underwent single-level TLIF (T group). The analyzed variables included global alignment, radiological parameters of fused segments, asymptomatic and symptomatic ASD incidence, clinical outcomes at 3 years postoperatively using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire data, visual analogue scale scores for low back pain, lower extremity pain, and lower extremity numbness. There was no significant change in global alignment between the two groups. The rate of improvement in anterior intervertebral disc height was not significantly different between the groups at 1-month postoperatively. However, at the final evaluation, the anterior intervertebral disc height and incidence of asymptomatic ASD were significantly higher in the O group. There was no significant difference in symptomatic ASD, reoperation cases, or clinical results between groups. Thus, single-level OLIF can maintain the corrected disc height, but as it has no effect on global alignment, its benefit is limited.

Abstract This study examined the factors that inhibit the therapeutic effects of cognitive behavioral therapy (CBT) and clarify the adaptation judgment criteria of CBT. We included patients with chronic low back pain and allocated them to the adaptation (with visual analog scale [VAS] improvement) or non-adaptation group (without VAS improvement). The patients were analyzed using various psychological tests. CBT improved depressive symptoms and catastrophic thinking; however, they were not correlated with the VAS and did not directly affect low back pain improvement. The non-adaptation group showed an unexplainable/vague sense of anxiety; an excessive focus on searching for pain; a strong intimacy desire; a strong tendency of medical dependency; and fantasy or distortion of the actual experience, especially self-image. Moreover, the patients showed a low ability to objectively express or attribute meaning to pain due to poor language skills, attention-deficit hyperactivity disorder, and emotional value judgment. Individuals with the aforementioned characteristics of pre-CBT psychological tests should select a different treatment approach given the high poor-adaption possibility. Even patients with depressive or anxious symptoms are not necessarily adaptable for CBT. Therefore, pre-CBT tests for treatment suitability are necessary. Future studies should establish a protocol for psychotherapy suitable for the non-adaptation group.

Introduction: Mirogabalin should be equivalent to pregabalin, but with fewer incidences of adverse drug reactions (ADRs). To verify these benefits in actual clinical trials, our study investigated the frequency of ADRs and mirogabalin's analgesic effects during treatment of peripheral neuropathic pain. Methods: This study included 74 patients with lower limb pain. We surveyed patient reports of ADRs during the follow-up period as the primary endpoint and examined the visual analog scale (VAS) reported for lower limb pain as the secondary endpoint (before administration, and two and four weeks after administration). Results: The occurrence of ADR was 27.0%, like the frequency of ADRs in the clinical trials for other disorders. However, the discontinuation rate of administration was 10.8%, which was significantly lower than the frequency of ADR occurrences. When the analgesic effect was assessed, a significant decrease in the temporal change of VAS for lower limb pain was observed before administration, and two and four weeks after administration. Conclusions: In this study, the occurrence of ADRs reported by the patients was like the frequency of ADRs reported in the clinical trials for other disorders. When assessing the analgesic effect, the temporal change of VAS for lower limb pain was found to decrease significantly before administration, and two and four weeks after administration.

Abstract Background Lumbar spinal disease causes disabilities in performing daily activities. Operative treatments are aimed at pain relief and rapid return to routine activity. Patient-based outcome measures are used to evaluate pathologies and therapeutic effects associated with lumbar spinal disease. Nevertheless, it remains unknown as to how much such treatment improves activity levels. The purpose of the current study was to measure changes in activity levels before and after lumbar spinal surgery using a wearable activity tracker and to analyze the differences between results and patient-based outcomes. Methods Sixty patients who underwent lumbar surgery were studied. The physical activity of participants was objectively evaluated using a wearable Micro-Motion logger system (Actigraph). We measured the amount of activity before and at 1, 3, 6, and 12 months after the surgery to evaluate postoperative changes. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, Roland-Morris Disability Questionnaire and visual analog scale were used to assess patient-based outcomes of pain and activities of daily living-related scores; we analyzed the relationships between scores and actual activity levels. Results The amount of actual activity decreased significantly 1 month after the surgery compared to that during the preoperative period, which then improved after 3 months postoperatively (p

Abstract Introduction Low back pain (LBP), a leading cause of global disability, is often associated with intervertebral disc degeneration (IDD). Exercise therapy is recommended for chronic LBP management and affects many tissues and organ systems. However, the ability of exercise to repair the extracellular matrix (ECM) in degenerating discs is unclear. The aims of the study were to examine mRNA expression of ECM structural components (collagen I, II, X, aggrecan) and regulators of matrix turnover (matrix metalloproteinases (MMP)‐3, − 9, − 13, ADAMTS‐4, − 5, TIMP1‐4, CCN2) between age‐matched (a) wild‐type and secreted protein acidic and rich in cysteine (SPARC)‐null, (b) sedentary and active, and (c) male and female mice. Methods At 8 months of age, male and female SPARC‐null and wild‐type control mice received a home cage running wheel or a control, fixed wheel for 6 months. Deletion of the SPARC gene results in progressive IDD beginning at 2 to 4 months of age. Increased activity was confirmed, and qPCR was performed on excised lumbar discs. Results Male SPARC‐null mice expressed less aggrecan mRNA than wild‐type controls. After 6 months of running, collagen, MMP3, and MMP13 expression was increased in male and MMP3 was increased in female SPARC‐null mice. Sex differences were observed in wild‐type mice and in response to IDD and long‐term running. Conclusions Voluntary running results in changes in mRNA consistent with increased ECM turnover and disc regeneration. Improved disc ECM might contribute to the beneficial effects of exercise on LBP and may create an intradiscal environment hospitable to regenerative therapies. Sex‐specific differences should be considered in the development of disc‐targeting therapies.

Introduction: Limb muscle mass measurement using dual-energy X-ray absorptiometry (DXA) is considered the gold standard for the diagnosis of sarcopenia. Moreover, bioelectrical impedance analysis (BIA) is also recognized as a beneficial tool considering its high correlation with DXA. However, it remains to be elucidated whether DXA and BIA can accurately measure trunk lean mass. The aim of this study was to investigate the correlation between DXA and BIA measurements of trunk muscle mass and the cross-sectional area (CSA) of trunk muscles measured using magnetic resonance imaging (MRI) and to compare measures of trunk muscle mass obtained using DXA and BIA in patients with low back pain (LBP). Methods: In total, 65 patients participated in the study. The correlation between DXA and BIA measurements and the CSA of trunk and paraspinal muscles at the L4-5 level were calculated. In addition, the correlation between DXA and BIA measurements of trunk muscle mass and the differences between these two measurements were determined. Results: The correlation coefficient between DXA and BIA trunk muscle mass measurement and trunk muscle CSA was 0.74 and 0.56 for men and 0.69 and 0.44 for women, respectively. DXA and BIA measurement values showed a significantly moderate correlation with the CSA of the erector spinae (ES) and psoas major (PM). The multifidus (MF) CSA did not correlate with measurements of DXA and BIA in both men and women. Although DXA and BIA measurements were significantly correlated, a significant difference between these two measurements was found. BIA overestimated the trunk muscle mass significantly compared with DXA. Conclusions: Trunk muscle mass measured with DXA and BIA was correlated with the CSA of most trunk muscles. Although the measurement of DXA and BIA showed a high correlation, BIA overestimated trunk muscle mass compared with DXA. Both DXA and BIA are beneficial for measuring trunk muscle mass.

Introduction: Wearable accelerometers can be used to evaluate waking and sleeping movements. Although a correlation between accelerometer data captured at the wrist and waist has been reported, it has not been evaluated in patients with low back pain. Therefore, this study aimed to evaluate correlations between movement measured at the wrist and waist, using wearable accelerometers, in patients with low back pain. Methods: Twenty patients with chronic low back pain and 20 healthy volunteers were enrolled. Two identical accelerometers were simultaneously worn by each participant, one on the nondominant wrist and the other at the waist, for 1 week. We compared the mean number of active movements and mean total amount of movement between the wrist and the waist to evaluate daytime and sleep activities. During sleep, we also evaluated sleep efficiency and time awake after sleep onset. Results: In daytime activity, the mean number of active movements and mean total amount of movement was greater for the wrist than for the waist, and the amount of waist movements relative to wrist movements was significantly lower in patients with low back pain than in healthy volunteers (p < 0.05). Despite these differences, the mean number of active movements and mean total amount of movement at the wrist and waist were strongly correlated in both groups. During sleep, although there was no difference in either measured sleep efficiency at the wrist or waist or time awake after sleep onset, measurements were strongly correlated in both groups. Conclusions: A strong correlation between movement data at the wrist and waist during both daytime activities and sleep was identified in patients with low back pain. Therefore, a wearable accelerometer worn on the wrist can reliably measure the movement of patients with low back pain, simplifying data capture for clinical and research purposes and improving patient comfort.

Introduction: To investigate the risk of epidural hematoma after spinous process-splitting laminectomy (SPSL). Methods: A total of 137 cases (mean age, 72.4 years; 68 men) of SPSL were included. Of these, there were instances (3.7%; mean age, 70.5 years; all male) of postoperative development of new neurologic deficit due to epidural hematoma requiring reoperation. The 133 subjects (72.5 years; 64 men) with normal postoperative course were used as controls, and comparisons were made between both groups using chi-squared and Student's t-tests. Regarding our investigation of risk factors for epidural hematoma, logistic regression was conducted with presence or absence of hematoma as our primary outcome variable, and age, gender, disease duration, number of laminectomies, which levels were decompressed, blood loss, length of case, drain output, coagulopathy, and whether or not there was an intraoperative dural tear were our explanatory variables. Results: All cases of hematoma were single-level laminectomies; there was one case of T9-10 and 3 cases of L2-3. In our direct comparison of both groups (hematoma versus control), the proportion of men was significantly higher in the hematoma group (100% versus 48%, p < 0.05); levels decompressed were also significantly higher (p < 0.05) in the hematoma group, and drain outputs were significantly lower (113 mL versus 234 mL, p < 0.05). From our logistic regression analysis, the levels were significantly higher (χ2 = 15, p = 0.0001) and the drain outputs were smaller (χ2 = 4.6, p = 0.03) in the hematoma group. Conclusions: Single-level decompression higher than the L2-3 level and reduced drain output were risk factors for spinal epidural hematoma. With this method of spinous process suturing and reconstruction there is less decompression compared with more conventional methods; therefore, the effect of hematoma may be more pronounced at higher vertebral levels with reduced canal width, and drain failure may also occur with this limited space.

Introduction: Causes of pain due to spinal metastases have been insufficiently investigated. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were the focus of this study. Both are known as proinflammatory cytokines associated with the pathophysiology of pain syndromes. It is well known that cancer cells produce these cytokines, but whether osteoclasts produce them as well remains unclear. We hypothesize that osteoclasts produce these cytokines; in other words, pain from spinal metastasis is stronger than pain from the primary tumor. Methods: We made a rat spinal metastasis model of breast cancer (metastasis group) and models with a hole in the vertebrae (puncture group) and resected the vertebrae. Tartrate-resistant acid phosphatase (TRAP) staining was performed to reconfirm that osteoclasts increase in vertebrae with spinal metastasis. We then evaluated TNF-α and IL-6 expression using immunohistochemistry and real-time polymerase chain reaction (PCR). Results: The results of TRAP staining showed that osteoclasts increase in metastatic vertebrae. The osteoclasts in the puncture models were TNF-α negative but were TNF-α positive in the metastasis model. The osteoclasts in the puncture models and metastasis model were both IL-6 positive. According to the real-time PCR results, TNF-α in vertebrae increased in the metastasis model, but IL-6 did not increase in the metastasis model compared with in the puncture model. Conclusions: The number of osteoclasts is higher in the metastasis model. While TNF in the osteoclasts increased in the spinal metastasis model, IL-6 did not. This probably means that breast cancer affects TNF production in osteoclasts. This increase of TNF-α may lead to pain from spinal metastasis.

Study Design A retrospective observational study was performed. Purpose We investigated the prevalence of sarcopenia in dropped head syndrome (DHS), and the relationship between biochemical markers, including major advanced glycation end products (AGEs), pentosidine, and DHS in older women. Overview of Literature AGEs have been implicated in the pathogenesis of sarcopenia. Methods We studied 13 elderly women with idiopathic DHS (mean age, 77.2 years) and 20 healthy volunteers (mean age, 74.8 years). We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass [kg]/[height (m)]2). Cervical sagittal plane alignment, including C2–C7 sagittal vertical axis (C2–C7SVA), C2–C7 angle, and C2 slope (C2S), was measured. Biochemical markers, such as serum and urinary pentosidine, serum homocysteine, 1, 25-dihydroxyvitamin D, and 25-hydroxyvitamin D, were measured. The level of each variable was compared between DHS and controls. The relationship between biochemical markers and DHS was examined. Results Sarcopenia (SMI

Nonalcoholic fatty liver disease (NAFLD) is a pathological condition caused by excess triglyceride deposition in the liver. The SMXA-5 severe fatty liver mouse model has been established from the SM/J and A/J strains. To explore the genetic factors involved in fatty liver development in SMXA-5 mice, we had previously performed quantitative trait locus (QTL) analysis, using (SM/J×SMXA-5)F2 intercross mice, and identified Fl1sa on chromosome 12 (centromere-53.06 Mb) as a significant QTL for fatty liver. Furthermore, isoamyl acetate-hydrolyzing esterase 1 homolog (Iah1) was selected as the most likely candidate gene for Fl1sa. Iah1 gene expression in fatty liver-resistant A/J-12SM mice was significantly higher than in fatty liver-susceptible A/J mice. These data indicated that the Iah1 gene might be associated with fatty liver development. However, the function of murine Iah1 remains unknown. Therefore, in this study, we created Iah1 knockout (KO) mice with two different backgrounds [C57BL/6N (B6) and A/J-12SM (A12)] to investigate the relationship between Iah1 and liver lipid accumulation. Liver triglyceride accumulation in Iah1-KO mice of B6 or A12 background did not differ from their respective Iah1-wild type mice under a high-fat diet. These results indicated that loss of Iah1 did not contribute to fatty liver. On the other hands, adipose tissue dysfunction causes lipid accumulation in ectopic tissues (liver, skeletal muscle, and pancreas). To investigate the effect of Iah1 deficiency on white adipose tissue, we performed DNA microarray analysis of epididymal fat in Iah1-KO mice of A12 background. This result showed that Iah1 deficiency might decrease adipokines Sfrp4 and Metrnl gene expression in epididymal fat. This study demonstrated that Iah1 deficiency did not cause liver lipid accumulation and that Iah1 was not a suitable candidate gene for Fl1sa.

Introduction: Thus far, few reports have described the time series histological variations in injured paravertebral muscle tissues for long durations, considering the type of pain. The purpose of this study is to evaluate histological changes in injured paravertebral muscles and dominant nerves considering the type of pain. Methods: We used 59 eight-week-old male Sprague-Dawley rats. A 115-g weight was dropped from a height of 1 m on the right paravertebral muscle. Fluoro-Gold (FG), a sensory nerve tracer, was injected into this muscle. Hematoxylin and eosin (HE) staining and nerve growth factor (NGF) immunostaining of the muscle were performed for histological evaluation. L2 dorsal root ganglia (DRG) on both sides were resected, and immunohistochemical staining was performed for calcitonin gene-related peptide (CGRP, a pain-related neuropeptide) and for activating transcription factor 3 (ATF3, a neuron injury marker). Each examination was performed at 3 days, 1-3 weeks, and 6 weeks after injury. Results: HE staining of the paravertebral muscle indicated infiltration of inflammatory cells and the presence of granulation tissue in the injured part on the ipsilateral side at 3 days and 1 week after the injury. Fibroblasts and adipocytes were present at 2-3 weeks. At 6 weeks, the injured tissue was almost completely repaired. NGF was detected at 2-3 weeks post injury and appeared to colocalize with fibroblasts, but was not observed at 6 weeks post injury. The percentage of cells double-labeled with FG and CGRP in FG-positive cells of the primary muscle was significantly higher in the injured side at 3 days and 1-3 weeks post injury (P < 0.05). However, at 6 weeks, no significant difference was observed. No significant expression of ATF3 was observed. Conclusions: These results suggest that sensitization of the dominant nerve in the DRG, in which NGF may play an important role, can protract pain in injured muscles.

Study Design Cross-sectional observational study. Purpose To compare measurements of appendicular skeletal muscle mass (ASMM) and whole fat mass (WFM) obtained using dualenergy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) among patients with low back pain (LBP). Moreover, the study investigated the correlation between BIA-based ASMM and DXA-based bone mineral density (BMD). Overview of the Literature If reliable, BIA may be a useful alternative to DXA as a screening tool for sarcopenia and osteoporosis among patients with LBP. Methods Measurements were performed in 130 patients, including BMD of the lumbar spine and femoral neck. The correlation between DXA and BIA as well as between BIA-ASMM and BMD were evaluated. Results BIA and DXA were highly correlated in both male and female patients (r =0.73–0.90, p

Introduction: Osteoporosis can produce a persistent state of pain known as osteoporotic pain. One proposed mechanism of this pathology is increased calcitonin gene-related peptide (CGRP; a marker related to inflammatory pain) expression in the dorsal root ganglia (DRG) innervating osteoporotic vertebrae. Alternatively, a previous study revealed that axial loading caused osteoporotic pain in a rodent model of coccygeal vertebrae compression. Because this compression model is associated with trauma, additional mechanistic studies of osteoporotic pain in the absence of trauma are required. The current study aimed to evaluate the expression and relative distribution of transient receptor potential vanilloid 4 (TRPV4), a pain-related mechanoreceptor, in ovariectomized (OVX) osteoporotic rats. Methods: CGRP-immunoreactive (-ir) and TRPV4-ir DRG neurons innervating the L3 vertebrae of Sprague-Dawley rats were labeled with a neurotracer, FluoroGold. Intravertebral pH was also measured during the neurotracer procedure. TRPV4-ir/CGRP-ir FluoroGold-positive DRG neurons were quantified in sham control and OVX rats (n = 10, ea). The threshold for statistical significance was set at P < 0.05. Results: There was no statistical difference in the number of FluoroGold-positive DRG neurons between groups; however, there were significantly more CGRP-ir/TRPV4-ir FluoroGold-positive DRG neurons in the OVX group compared with the sham control group (P < 0.05) as well as the significantly increased molecular production of each peptide. Intravertebral pH was also lower in the OVX group compared with the sham control group (P < 0.05). Conclusion: Sensory neurons innervating osteoporotic vertebrae exhibited increased expression of co-localized CGRP and TRPV4 in OVX osteoporotic rats. Additionally, intravertebral pH was low in the vicinity osteoporotic vertebrae. Considering that TRPV4 is a mechanosensitive nociceptor that is activated in acidic environments, its upregulation may be associated with the pathology of osteoporotic pain derived from microinflammation involved in osteoporosis.

Study Design Retrospective observational study. Purpose We considered the relationship between spinal alignment and skeletal muscle mass on clinical outcomes following a surgery for lumbar spinal stenosis (LSS). Overview of Literature There are no reports of preoperative factors predicting residual low back pain following surgery for LSS. Methods Our target population included 34 women (mean age, 74.4 years) who underwent surgery for LSS. Prior to and 6 months after the surgery, systemic bone mineral density and lean soft tissue mass were measured using dual-energy X-ray absorptiometry. Skeletal muscle mass index (SMI) was calculated as the sum of the arm and leg lean mass in kilograms divided by height in meters squared. The spinal alignment was also measured. Clinical outcomes were evaluated using the Japanese Orthopedic Association scoring system, leg and low back pain Visual Analog Scale, and Roland–Morris Disability Questionnaire (RDQ). Additionally, we examined the bone mineral density, skeletal muscle mass, and spinal alignment before and after the surgery. We used the Spearman correlation coefficient to examine the associations among clinical outcomes, preoperative muscle mass, and spinal alignment. Results Sarcopenia (SMI 6.12), RDQ was significantly higher in subjects with sarcopenia (p =0.04). RDQ was significantly negatively correlated with SMI (r =−0.42, p

Introduction: Osteoporosis and sarcopenia are said to be similar disorders. However, few reports have described the effects of anti-osteoporosis drugs on muscle mass in clinical practice. Methods: We selected 150 postmenopausal women with osteoporosis treated by minodronate (osteoporosis medication [OM] group) and 50 postmenopausal women without osteoporosis who did not receive treatment (no osteoporosis [NO] group). The OM group was further divided into two treatment subgroups: a combination of monthly minodronate and daily activated vitamin D vs. monthly minodronate alone. We measured lumbar spine and femoral neck bone mineral density (BMD) with dual-energy X-ray absorptiometry and muscle mass of the upper limbs, lower limbs, and trunk with bioelectrical impedance analysis at baseline and after 6 months. Results: The OM and NO groups contained 130 and 37 patients, respectively (mean age: 73.9 ± 8.3 and 74.1 ± 10.0 years, respectively). In the OM group, lumbar spine BMD significantly increased after 6 months, while lower limb muscle mass significantly decreased. In the NO group, lumbar spine BMD and lower limb muscle mass did not significantly change after 6 months. In the OM group, BMD of the lumbar spine significantly increased but the lower limb muscle mass significantly decreased after 6 months relative to the NO group. In the combination therapy subgroup of the OM group muscle mass decreased significantly less than in the minodronate-alone subgroup. Conclusions: In postmenopausal women with osteoporosis, minodronate can increase BMD but cannot increase muscle mass. However, simultaneous use of activated vitamin D can suppress muscle mass decrease. The combination of activated vitamin D and minodronate may be useful for treating osteoporosis in postmenopausal women.

Introduction: Discogenic back pain remains poorly understood with respect to etiopathogenesis, despite being a considerable burden. We sought to examine the expression of vascular endothelial growth factor in injured intervertebral discs in rat caudal vertebrae. Methods: Forty-eight male Sprague Dawley rats were assigned to 2 groups according to disc puncture injury: puncture (n = 32) or non-puncture (n = 16). Disc puncture was performed percutaneously such that the incision would be in the primary plane of motion for the coccygeal discs 5-6, 6-7, and 7-8. A 26-gauge needle was used to puncture each disc 10 times. Punctured discs were examined histologically by hematoxylin and eosin staining at 1, 7, 14, and 28 days post-injury. Results: Vascular endothelial growth factor was localized immunohistochemically, and determined quantitatively using an enzyme-linked immunosorbent assay. Peak inflammation occurred on the 7th day post-injury, but tissue degeneration continued until day 28. Local expression of vascular endothelial growth factor tended to be highest in the annulus fibrosus on the 7th and 14th days after puncture injury. The level of vascular endothelial growth factor was highest 1-day post-injury, and then gradually decreased thereafter. Furthermore, vascular endothelial growth factor levels in the puncture group were significantly higher than those in the non-puncture control group (p < 0.05). Conclusions: We found increased expression of the inflammatory cytokine vascular endothelial growth factor in injured intervertebral discs, suggesting that vascular endothelial growth factor may be clinically important in discogenic back pain.

Introduction: Failed spinal fusion surgery sometimes requires salvage surgery when symptomatic, especially with postsurgical decrease in intervertebral disc height followed by foraminal stenosis. For such cases, an anterior approach to lumbar lateral interbody fusion (LLIF) provides safe, direct access to the pathological disc space and a potential improvement in the fusion rate. One LLIF approach, oblique lateral interbody fusion (OLIF), targets the oblique lateral window of the intervertebral discs to achieve successful lateral interbody fusion. The current technical note describes spinal revision surgery using the OLIF procedure. Technical Note: The subjects were patients with leg pain and/or lower back pain derived from decreased intervertebral height followed by foraminal stenosis due to failed spinal fusion surgery. These patients underwent additional OLIF surgery and posterior fusion with no additional posterior direct decompression. Their outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scores at baseline and final follow-up. Bony union was also evaluated using computed tomography images at final follow-up. Six subjects were evaluated, with two representative cases described in detail. Four patients had an adjacent segment disorder, and the other two patients had pseudarthrosis due to postoperative infection. The mean JOA score improved from 5.7 ± 5.4 to 21.2 ± 2.3, with a mean recovery rate of 65.0%. All cases showed intervertebral bony union. Conclusions: We introduced a salvage strategy for failed posterior spine fusion surgery cases using the OLIF procedure. Patients effectively achieved recovered intervertebral and foraminal height with no additional posterior direct decompression.

Abstract Background Nerve growth factor (NGF) is not only an important factor in nerve growth but also a major contributor to the production of inflammation. It has been reported that inhibiting NGF could reduce several types of pain in several animal models. Here, we aimed to clarify the efficacy of NGF antibody in a knee osteoarthritis (OA) pain model in mice. Method Six-week-old male C57BR/J mice were used (n = 30). Ten mice comprised the control group, which received saline injection into the right knee joints; the other 20 mice comprised the experimental group, which received monoiodoacetate (MIA) injection into the right knee joints. Three weeks after surgery, the 20 experimental mice were randomly placed into treatment groups which received either sterile saline (non-treat group: 10 mg/kg, i.p.) or an anti-NGF antibody (anti-NGF group: 10 mg/kg, i.p.). Simultaneously, all mice received fluorogold (FG) retrograde neurotracer injection into their right joints. In a behavioral study, we evaluated gait using the CatWalk quantitative gait analysis system before surgery, 3 weeks after surgery (before treatment), 4 weeks after surgery (one week after surgery), and 5 weeks after surgery (2 weeks after surgery). In immunohistochemical analysis, the right dorsal root ganglia (DRGs) from the L4–L6 levels were resected 5 weeks after surgery (2 weeks after surgery). They were immunostained for calcitonin gene-related peptide (CGRP), and the number of FG-labeled or CGRP-immunoreactive (IR) DRG neurons was counted. Results On gait analysis using the CatWalk system, duty cycle, swing speed, and print area were decreased in non-treat group compared with those in control group and improved in the anti-NGF group compared with those in non-treat group. CGRP expression in DRGs was up-regulated in non-treat group compared with that in control group and suppressed in the anti-NGF group compared with that in non-treat group (both p

Study DesignAn experimental animal study.PurposeTo evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin gene-related peptide (CGRP) in the dorsal ganglia in a rat model.Overview of LiteratureIncreased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury.MethodsThrough abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti-VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 µg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 µL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1–L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP.ResultsCompared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p

Introduction: Osteoporosis is a pathological state with an unbalanced bone metabolism mainly caused by accelerated osteoporotic osteoclast activity due to a postmenopausal estrogen deficiency, and it causes some kinds of pain, which can be divided into two types: traumatic pain due to a fragility fracture from impaired rigidity, and pain derived from an osteoporotic pathology without evidence of fracture. We aimed to review the concepts of osteoporosis-related pain and its management. Methods: We reviewed clinical and basic articles on osteoporosis-related pain, especially with a focus on the mechanism of pain derived from an osteoporotic pathology (i.e., osteoporotic pain) and its pharmacological treatment. Results: Osteoporosis-related pain tends to be robust and acute if it is due to fracture or collapse, whereas pathology-related osteoporotic pain is vague and dull. Non-traumatic osteoporotic pain can originate from an undetectable microfracture or structural change such as muscle fatigue in kyphotic patients. Furthermore, basic studies have shown that the osteoporotic state itself is related to pain or hyperalgesia with increased pain-related neuropeptide expression or acid-sensing channels in the local tissue and nervous system. Traditional treatment for osteoporotic pain potentially prevents possible fracture-induced pain by increasing bone mineral density and affecting related mediators such as osteoclasts and osteoblasts. The most common agent for osteoporotic pain management is a bisphosphonate. Other non-osteoporotic analgesic agents such as celecoxib have also been reported to have a suppressive effect on osteoporotic pain. Conclusions: Osteoporotic pain has traumatic and non-traumatic factors. Anti-osteoporotic treatments are effective for osteoporotic pain, as they improve bone structure and the condition of the pain-related sensory nervous system. Physicians should always consider these matters when choosing a treatment strategy that would best benefit patients with osteoporotic pain.

Study DesignObservational study.PurposeTo assess the correlation among inflammatory cytokine expression levels, degree of intervertebral disk (IVD) degeneration, and predominant clinical symptoms observed in degenerative disk disease (DDD).Overview of LiteratureLow back pain (LBP) is associated with inflammatory cytokine expression levels, including those of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and nerve growth factor (NGF). However, the association between cytokine expression levels and the physiological mechanisms of disk degeneration and clinical pain remain controversial.MethodsUsing the enzyme-linked immunosorbent assay, TNF-α, IL-6, and NGF expression levels were analyzed in 58 IVD samples that were harvested from patients with lumbar DDD. Patient samples were grouped according to the degree of IVD degeneration using the Pfirrmann grading system and magnetic resonance imaging, and the correlations between the disease groups and each cytokine expression level were assessed. In addition, on the basis of their predominant preoperative symptoms, the patients were assigned to either an LBP or leg pain group to determine the correlation among these disease manifestations and individual cytokine expression levels.ResultsA gradual increase in TNF-α (R=0.391) and IL-6 (R=0.388) expression levels correlated with the degree of IVD degeneration, whereas NGF (R=0.164) expression levels exhibited a minimal decrease with disease progression. Regarding the predominant clinical manifestation, only the LBP group exhibited a significant increase in TNF-α expression levels (p=0.002).ConclusionsThese results suggested that TNF-α and IL-6 play an important role in the pathophysiology of IVD degeneration at any stage, whereas NGF plays an important role during the early disease stages. Moreover, because TNF-α expression levels were significantly high in the LBP group, we propose that they are involved in LBP onset or progression.

Study DesignRetrospective case series.PurposeThe purpose of this study was to determine whether discontinuing teriparatide treatment and replacing it with bisphosphonate treatment maintains the volume of the fusion mass after posterolateral fusion (PLF) in women with postmenopausal osteoporosis.Overview of LiteratureClinical data support the efficacy of parathyroid hormone (PTH) for lumbar PLF. However, the use of PTH is limited to 2 years.MethodsWe treated 19 women diagnosed with osteoporosis and degenerative spondylolisthesis with teriparatide (20 µg daily subcutaneously). All patients underwent one-level instrumented PLF. Teriparatide was used during 2 months prior to surgery and more than 8 months after surgery. After discontinuing teriparatide treatment, all patients used bisphosphonate (17.5 mg risedronate weekly, oral administration). Area of the fusion mass across the transverse processes at one segment was determined on an anteroposterior radiograph at 1, 2, and 3 years after surgery.ResultsWe followed 19 patients for 3 years. The average duration of teriparatide treatment was 11.5 months. The bone union rate was 95%. The average area of the bone fusion mass was not significantly different between the right and left sides at 1, 2, or 3 years after surgery (p>0.05).ConclusionsThis study showed that replacing teriparatide treatment with bisphosphonate maintained the bone fusion mass volume after PLF in women with postmenopausal osteoporosis.

Study DesignRetrospective, observational, single-center study.PurposeTo investigate the long-term outcomes of in situ fusion procedures for treating dysplastic spondylolisthesis.Overview of LiteratureIn situ fusion performed in patients with dysplastic spondylolisthesis avoids the development of nerve complications.MethodsIn total, 12 of 28 patients who underwent in situ fusion for treating dysplastic spondylolisthesis at Chiba University Hospital from 1974 to 2004 were followed up in August 2013. Surgical complications were evaluated. Low back pain and leg pain were assessed using a visual analog scale (VAS). Vertebral alignment, including the lumbosacral angle and lumbar lordosis angle measurement on radiographic images (profile view in the neutral standing position), was evaluated during preoperative, postoperative, and final examinations.ResultsThe mean follow-up duration, patient age at the final examination, and patient age at operation were 20.0±7.2, 42.3±13.3, and 22.3±11.4 years, respectively. No complications were reported. Mean VAS scores for low back pain and leg pain were significantly lower at the final examination than at the preoperative examination (p

Much progress has been made in neuroimaging with Magnetic Resonance neurography and Diffusion Tensor Imaging (DTI) owing to higher magnetic fields and improvements in pulse sequence technology. Reports on lumbar nerve DTI have also increased considerably. Many studies have shown that the use of DTI in lumbar nerve lesions, such as lumbar foraminal stenosis and lumbar disc herniation, makes it possible to capture images of interruptions of tractography at stenotic sties, enabling the diagnosis of stenosis. DTI can also reveal significant decreases in fractional anisotropy (FA) with significant increases in apparent diffusion coefficient (ADC) values in compression lesions. FA values have higher accuracy than ADC values. Furthermore, strong correlations exist between FA values and indications of neurological severity, including the Japanese Orthopedic Association (JOA) score, the Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RDQ) in patients with lumbar disc herniation-induced radiculopathy. Most lumbar DTI has become 3T; 3T MRI has made it possible to take high-resolution DTI measurements in a short period of time. However, increased motion artifacts in the magnetic susceptibility effect lead to signal irregularities and image distortion. In the future, high-resolution DTI with reduced field-of-view may become useful in clinical applications, since visualization of nerve lesions and quantification of DTI parameters could allow more accurate diagnoses of lumbar nerve dysfunctions. Future translational studies will be necessary to successfully bring MR neuroimaging of lumbar nerve into clinical use.

Study DesignRetrospective case series.PurposeThe purpose of this study was to examine changes in the ligamentum flavum thickness and remodeling of the spinal canal after anterior fusion during a 10-year follow-up.Overview of LiteratureExtreme lateral interbody fusion provides minimally invasive treatment of the lumbar spine; this anterior fusion without direct posterior decompression, so-called indirect decompression, can achieve pain relief. Anterior fusion may restore disc height, stretch the flexure of the ligamentum flavum, and increase the spinal canal diameter. However, changes in the ligamentum flavum thickness and remodeling of the spinal canal after anterior fusion during a long follow-up have not yet been reported.MethodsWe evaluated 10 patients with L4 spondylolisthesis who underwent stand-alone anterior interbody fusion using the iliac crest bone. Magnetic resonance imaging was performed 10 years after surgery. The cross-sectional area (CSA) of the dural sac and the ligamentum flavum at L1–2 to L5–S1 was calculated using a Picture Archiving and Communication System.ResultsSpinal fusion with correction loss (average, 4.75 mm anterior slip) was achieved in all patients 10 years postsurgery. The average CSAs of the dural sac and the ligamentum flavum at L1–2 to L5–S1 were 150 mm2 and 78 mm2, respectively. The average CSA of the ligamentum flavum at L4–5 (30 mm2) (fusion level) was significantly less than that at L1–2 to L3–4 or L5–S1. Although patients had an average anterior slip of 4.75 mm, the average CSA of the dural sac at L4–5 was significantly larger than at the other levels.ConclusionsSpinal stability induced a lumbar ligamentum flavum change and a sustained remodeling of the spinal canal, which may explain the long-term pain relief after indirect decompression fusion surgery.

Study DesignAnimal model study.PurposeThe purpose of this study was to evaluate the histological variation in the injured muscle and production of calcitonin gene-related peptide in rats over time.Overview of LiteratureVertebral surgery has been reported to cause atrophy of the back muscles, which may result in pain. However, few reports have described the time series histological variation in the injured muscle and changes in the dominant nerve.MethodsWe used 30 male, 8-week-old Sprague-Dawley rats. The right and left sides of the paravertebral muscle were considered as the injured and uninjured sides, respectively. A 115 g weight was dropped from a height of 1 m on the right paravertebral muscle. Hematoxylin and eosin (H&E) staining of the muscle was performed 1–3 weeks after injury for histological evaluation. Fluoro-Gold (FG) was injected into the paravertebral muscle. The L2 dorsal root ganglia on both sides were resected 1, 2, and 3 weeks after injury, and immunohistochemical staining for calcitonin gene-related peptide was performed.ResultsH&E staining of the paravertebral muscle showed infiltration of inflammatory cells and the presence of granulation tissue in the injured part on the ipsilateral side 1 week after injury. Muscle atrophy occurred 3 weeks after injury, but was repaired via spontaneous replacement of muscle cells/fibers. In contrast, compared with the uninjured side, the percentage of cells double-labeled with FG and calcitonin gene-related peptide in FG-positive cells in the dorsal root ganglia of the injured side was significantly increased at each time point throughout the study period.ConclusionsThese results suggest that sensitization of the dominant nerve in the dorsal root ganglia, which may be caused by cicatrix formation, can protract injured muscle pain. This information may be helpful in elucidating the underlying mechanism of persistent pain after back muscle injury.

Purpose: We examined duloxetine's effectiveness in the treatment of neuropathic pain in patients who were intolerant to continuous pregabalin administration. Materials and Methods: The present study is a retrospective study of patients diagnosed with neuropathic pain with neuropathic leg pain as the chief complaint. We analyzed 20 cases in which pregabalin was changed to duloxetine because of adverse effects (16 cases) or treatment failure (4 cases). The incidence of adverse events after duloxetine administration was used as the primary endpoint, with the secondary endpoint being the leg pain level based on a numerical rating scale (NRS). Results: The incidence of adverse events after starting duloxetine was 40%. Average leg pain scores measured on the NRS were 8.4±1.4, 6.4±1.4, and 4.1±2.0 at the time of the patients' first visit, pregabalin discontinuation, and after switching to duloxetine, respectively. A significant difference in NRS scores was found between the first visit and pregabalin discontinuation and also between pregabalin discontinuation and after the switch to duloxetine (p0.05). Conclusion: When patients with neuropathic pain are unable to tolerate pregabalin because of adverse effects, changing the medication to duloxetine may be an option.

Study DesignRetrospective case series.PurposeTo examine the efficacy of TachoSil for vessel injury in 6 patients who underwent anterior lumbar fusion surgery (ALF).Overview of LiteratureALF for the lumbar spine has a high rate of success, although intraoperative concerns and iatrogenic complications are known, and injury of a major vessel is sometimes a complication. The efficacy of TachoSil, a fibrin-based hemostat, has been reported for several types of surgery; however, use of TachoSil for ALF surgery has not been described. Here, we report on the efficacy of TachoSil in 6 patients, who underwent ALF after vascular surgeons having difficulty in repairing vessels.MethodsTwo man and 4 women with average age of 50.8±10.9 (mean±standard deviation) were diagnosed with a vertebral tumor (2 patients), L4 degenerative spondylolisthesis (2 patients), and L5 spondylolytic spondylolisthesis (2 patients) and underwent ALF. The blood vessels injured included the common iliac vein in 2 patients and a branch of a segmental artery from the aorta in 4 patients. We consulted a vascular surgeon to suture or repair the vessels during surgery, and although the vascular surgeon attempted to address the injuries, suturing or repair was not possible in these cases. For this reason, we used TachoSil to repair the injury in the vessels walls or to stop the bleeding.Results Time to pressure hemostasis using TachoSil was 34±12 minutes, and total blood loss was 1,488±1,711 mL. Nevertheless, all vessel injuries were controlled by the use of TachoSil.ConclusionsWe recommend the use of TachoSil for vessel injuries that vascular surgeons cannot suture or repair during ALF surgery.

Study DesignRetrospective study.PurposeTo determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain.Overview of LiteratureInadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging.MethodsPatients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed.ResultsNo adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p

Study DesignExperimental animal study.PurposeWe aimed to determine the optimal dose of a single direct injection of the tumor necrosis factor (TNF)-α inhibitor, etanercept, by using the rat model of degenerative intervertebral disc from injury.Overview of LiteratureThe pain-related peptide expression was suppressed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner.MethodsThe neurotracer FluoroGold (FG) was applied to the surfaces of L4/5 discs to label their innervating dorsal root ganglion (DRG) neurons (n=50). Ten rats were included in the nonpunctured disc sham surgery control group, whereas the other 40 were included in the experimental group in which intervertebral discs were punctured with a 23-gauge needle. Saline or etanercept (10 µg, 100 µg, or 1,000 µg) was injected into the punctured discs (n=10 for each treatment). After 14 days of surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP). The proportion of FG-labeled CGRP-immunoreactive DRG neurons was evaluated in all the groups.ResultsThere were no significant differences between the puncture+saline group and the puncture+10-µg etanercept group (p >0.05). However, a significant decrease in the percentage of FG and CGRP double-positive cells in FG-positive cells was observed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner (p

Study DesignRetrospective case series.PurposeTo determine whether symptoms predict surgical outcomes for patients with discogenic low back pain (DLBP).Overview of LiteratureSpecific diagnosis of DLBP remains difficult. Worsening of pain on flexion is a reported symptom of DLBP. This study sought to determine whether symptoms predict surgical outcomes for patients with DLBP.MethodsWe investigated 127 patients with low back pain (LBP) and no dominant radicular pain. Magnetic resonance imaging was used to select patients with disc degeneration at only one level. If pain was provoked during discography, we performed fusion surgery (87 patients). Visual analogue scale score and responses to a questionnaire regarding symptoms including worsening of pain on flexion or extension were assessed. Symptom sites before surgery were categorized into LBP alone, or LBP plus referred inguinal or leg pain. We followed 77 patients (average 3.0 years) and compared symptoms before surgery with surgical outcome.ResultsSixty-three patients with a good outcome showed postsurgical pain relief (≥60% pain relief) and 14 patients with a poor outcome did not (

Study DesignRetrospective case series.PurposeTo classify back muscle degeneration using magnetic resonance imaging (MRI) and investigate its relationship with back pain after surgery.Overview of LiteratureBack muscle injury and degeneration often occurs after posterior lumbar surgery, and the degeneration may be a cause of back pain. However, the relationship between back muscle degeneration and back pain remains controversial.MethodsA total of 84 patients (average age, 65.1 years; 38 men, 46 women) with lumbar spinal stenosis underwent posterior decompression surgery alone. MRI (1.5 tesla) was evaluated before and more than a year after surgery in all patients. Muscle on MRI was classified into three categories: low intensity in T1-weighted imaging, high intensity in T2-weighted imaging (type 1), high intensity in both T1- and T2-weighted images (type 2), and low intensity in both T1- and T2-weighted imaging (type 3). The prevalence of the types and their relationship with back pain (determined on a visual analog scale) were evaluated.ResultsMRI revealed muscle degeneration in all patients after surgery (type 1, 6%; type 2, 82%; and type 3, 12%). Type 2 was significantly more frequent compared with types 1 and 3 (p0.05).ConclusionsVarious pathologies of back muscle degeneration after posterior lumbar surgery were revealed. Type 2 (fatty) change was most frequent, and other patients had type 3 (scar) or type 1 (inflammation or water-like) changes. According to the Modic classification of bone marrow changes, Modic type 1 change is associated with inflammation and back pain. However, no particular type of back muscle degeneration was correlated with back pain after surgery.

Study DesignRetrospective observational study.PurposeTo examine fractional anisotropy (FA) values and apparent diffusion coefficient (ADC) values of damaged nerves to discriminate between lumbar intraspinal stenosis (IS) and foraminal stenosis (FS) using diffusion tensor imaging (DTI)Overview of LiteratureIt is important in the selection of surgical procedure to discriminate between lumbar IS and FS, but such discrimination is difficult.MethodsThere were 9 cases of IS, 7 cases of FS, and 5 healthy controls. The regions of interest were established in the lumbar intraspinal zone (Iz), nerve root (N), and extraforaminal zone (Ez). The FA and ADC values were measured on the affected and unaffected sides of the nerves. The FA ratio and the ADC ratio were calculated as the affected side/unaffected side ×100 (%).ResultsIn the Ez, the FA value was significantly lower in FS than in IS (p

Diagnosis of lumbar foraminal stenosis remains difficult. Here, we report on a case in which bilateral lumbar foraminal stenosis was difficult to diagnose, and in which diffusion tensor imaging (DTI) was useful. The patient was a 52-year-old woman with low back pain and pain in both legs that was dominant on the right. Right lumbosacral nerve compression due to a massive uterine myoma was apparent, but the leg pain continued after a myomectomy was performed. No abnormalities were observed during nerve conduction studies. Computed tomography and magnetic resonance imaging indicated bilateral L5 lumbar foraminal stenosis. DTI imaging was done. The extraforaminal values were decreased and tractography was interrupted in the foraminal region. Bilateral L5 vertebral foraminal stenosis was treated by transforaminal lumbar interbody fusion and the pain in both legs disappeared. The case indicates the value of DTI for diagnosing vertebral foraminal stenosis.

Abstract. Introduction:. The prevalence of osteoporosis is increasing with the aging population and is associated with increased risk of fracture and chronic pain. Osteoporosis is currently treated with bisphosphonate therapy to attenuate bone loss. We previously reported that improvement in bone mineral density is not sufficient to reduce osteoporosis-related pain in an ovariectomy (OVX)-induced mouse model of osteoporosis, highlighting the need for new treatments. Targeting of nerve growth factor (NGF) with sequestering antibodies is a promising new direction for the treatment of musculoskeletal pain including back pain and arthritis. Its efficacy is currently unknown for osteoporotic pain. Objective:. To investigate the efficacy of anti-NGF antibody therapy on osteoporotic pain in an OVX-induced mouse model. Methods:. Ovariectomy- and sham-operated mice were injected with an anti-NGF antibody (10 mg/kg, intraperitoneally, administered 2×, 14 days apart), and the effect on behavioural indices of osteoporosis-related pain and on sensory neuron plasticity was evaluated. Results:. Treatment with anti-NGF antibodies attenuated OVX-induced hypersensitivity to mechanical, cold, and heat stimuli on the plantar surface of the hind paw. The OVX-induced impairment in grip force strength, used here as a measure of axial discomfort, was partially reversed by anti-NGF therapy. No changes were observed in the rotarod or open-field tests for overall motor function and activity. Finally, anti-NGF treatment attenuated the increase in calcitonin gene-related peptide–immunoreactive dorsal root ganglia neurons observed in OVX mice. Conclusion:. Taken together, these data suggest that anti-NGF antibodies may be useful in the treatment of prefracture hypersensitivity that is reported in 10% of patients with osteoporosis.

Study DesignRetrospective case series.PurposeTo examine the most effective duration of teriparatide use for spinal fusion in women with postmenopausal osteoporosis.Overview of LiteratureWe reported that daily subcutaneous injection of teriparatide (parathyroid hormone) significantly improved bone union after instrumented lumbar posterolateral fusion (PLF) in women with postmenopausal osteoporosis when compared with oral administration of bisphosphonate. However, the most effective duration of teriparatide use for spinal fusion has not been explored.MethodsForty-five women with osteoporosis diagnosed with degenerative spondylolisthesis from one of the three treatment groups were evaluated based on: short-duration treatment (average, 5.5 months; n=15; daily subcutaneous injection of 20 µg teriparatide), long-duration treatment (average, 13.0 months; n=15; daily subcutaneous injection of 20 µg teriparatide), and bisphosphonate treatment (average, 13.0 months; n=15; weekly oral administration of 17.5 mg risedronate). All patients underwent PLF with a local bone graft. Fusion rate and duration of bone union were evaluated 1.5 years after surgery.ResultsBone union rate and average duration for bone union were 92% and 7.5 months in the long-duration treatment group, 80% and 8.5 months in the short-duration treatment group, and 70% and 10.0 months in the bisphosphonate treatment group, respectively. Results of bone union rate and average duration for bone union in the teriparatide treatment groups were significantly superior to those in the bisphosphonate treatment group (p

Study DesignProspective case series.PurposeTo examine the clinical efficacy of mini-open anterior retroperitoneal lumbar interbody fusion: oblique lateral interbody fusion (OLIF) for degenerated lumbar spinal kyphoscoliosis.Overview of LiteratureThe existing surgical procedures for the treatment of spinal kyphotic deformity, including Smith-Petersen osteotomy, pedicle subtraction osteotomy, and vertebral column resection procedures, are invasive in nature. Extreme lateral interbody fusion to provide less invasive treatment of the deformity has been reported, but complications including spinal nerve and psoas muscle injury have been noted. In the current study, we examined the clinical efficacy and complications of OLIF for degenerated lumbar spinal kyphoscoliosis.MethodsTwelve patients with degenerated lumbar spinal kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with open pedicle screws or percutaneous pedicle screws, without real-time monitoring by electromyography. Visual analog scale score and Oswestry disability index were evaluated before and 12 months after surgery, and fusion rate at OLIF cage, correction of the deformity, total blood loss, and surgical complications were also evaluated.ResultsPain scores significantly improved after surgery (p

Study DesignCase series.PurposeTo determine the utility of "PainVision" apparatus for the assessment of low back pain.Overview of LiteratureA newly developed device, the PainVision PS-2100 (Nipro, Osaka, Japan), has been used to assess the perception of pain in a quantitative manner. In the current study, we aimed to evaluate the efficacy of PainVision for the assessment of low back pain.MethodsWe assessed 89 patients with low back pain. The numeric rating scale (NRS) score, McGill Pain Questionnaire (MPQ) score and the degree of pain calculated by PainVision were measured twice at 4-week intervals in each patient. An electrode was patched on the forearm surface of the patients and the degree of pain was automatically calculated (degree of pain=100×[current producing pain comparable with low back pain-current at perception threshold/current at perception threshold]). Correlations between NRS and MPQ scores and the degree of pain were determined using Spearman's rank correlation test.ResultsThere was a strong correlation between the NRS and MPQ scores at each time point (rs=0.60, p

Although the pathological changes in osteoporotic bones are well established, the characterization of the osteoporotic pain and its appropriate treatment are not fully elucidated. We investigated the behavioral signs of cutaneous and deep musculoskeletal pain and physical function; time-dependent changes in bone mineral density (BMD) and the emergence of the behavioral phenotype; and the effects of pharmacological interventions having different mechanisms of action (chronic intraperitoneal administration of pamidronate [0.25 mg/kg, 5x/week for 5 weeks] versus acute treatment with intraperitoneal morphine [10 mg/kg] and pregabalin [100 mg/kg]) in a mouse model of ovariectomized or sham-operated mice 6 months following surgery. We observed reduced BMD associated with weight gain, referred cutaneous hypersensitivity, and deep musculoskeletal pain that persisted for 6 months. Chronic bisphosphonate treatment, 6 months after ovariectomy, reversed bone loss and hypersensitivity to cold, but other behavioral indices of osteoporotic pain were unchanged. While the efficacy of acute morphine on cutaneous pain was weak, pregabalin was highly effective; deep musculoskeletal pain was intractable. In conclusion, the reversal of bone loss alone is insufficient to manage pain in chronic osteoporosis. Additional treatments, both pharmacological and nonpharmacological, should be implemented to improve quality of life for osteoporosis patients.

Spinal metastasis of differentiated thyroid cancer can have a favorable prognosis if radical surgery is performed. We encountered a case of spinal metastasis involving three anterior vertebral bodies at the posterior element fusion level and successfully achieved adequate stability by radical surgery involving only the anterior elements. A 67-year-old woman who had numbness and muscle weakness in the lower limbs caused by metastatic spinal tumor at the posterior element fusion level of L1–L3 vertebrae was treated with radical surgery of only the anterior element to gain stability. Similar situations may occur in cases involving other malignant tumor metastases or spinal primary tumors. If such a case occurs, this method could be useful in preventing metastasis to the posterior element.

Study DesignExperimental animal study.PurposeTo evaluate pain-related behavior and changes in glial activity in the spinal dorsal horn after combined sciatic nerve compression and nucleus pulposus (NP) application in rats.Overview of LiteratureMechanical compression and inflammation caused by prostaglandins and cytokines at disc herniation sites induce pain. Structural changes and pain-associated cytokines in the dorsal root ganglia and spinal dorsal horn contribute to prolonged pain. Glial cells in the spinal dorsal horn may also function in pain transmission.MethodsThe sciatic nerve was compressed with NP for 2 seconds using forceps in the NP+nerve compression group; the sham-operated group received neither compression nor NP; and the control group received no operation. Mechanical hyperalgesia was measured for 3 weeks using von Frey filaments. Glial activity in the spinal dorsal horn was examined 7 days and 14 days postsurgery using anti-glial fibrillary acidic protein and anti-Ionized calcium binding adaptor molecule-1 antibodies to detect astrocytes and microglia, respectively.Results Mechanical hyperalgesia was detected throughout the 14-day observation in the NP+nerve compression group, but not in control or sham-operated groups (p

Study DesignExperimental animal study.PurposeTo evaluate pain-related behavior and changes in nuclear factor-kappa B (NF-kB), receptor activator of NF-kB (RANK), and ligand (RANKL) in dorsal root ganglia (DRG) after combined sciatic nerve compression and nucleus pulposus (NP) application in rats.Overview of LiteratureThe pathological mechanisms underlying pain from lumbar-disc herniation have not been fully elucidated. RANKL are transcriptional regulators of inflammatory cytokines. Our aim was to evaluate pain-related behavior and RANKL expression in DRG after sciatic-nerve compression and application of NP in rats.MethodsMechanical hyperalgesia and RANKL expression were assessed in three groups of rats: NP+sciatic nerve compression (2 seconds), sham-operated, and controls (n=20 each). Mechanical hyperalgesia was measured every other day for 3 weeks using von Frey filaments. RANKL expression in L5 DRGs was examined at five and ten days after surgery using immunohistochemistry.ResultsMechanical hyperalgesia was observed over the 12-day observation period in the NP+nerve compression group, but not in the control and sham-operated animal groups (p