Abstract Background context Although explored in humans and animal models, the pathomechanisms of discogenic low back pain (LBP) remain unknown. Purpose The aim of this study was to review the ...literature about the pathomechanisms of discogenic LBP. Methods Animal models of discogenic pain and specimens from degenerated human intervertebral discs (IVDs) have provided clues about the pathomechanisms of discogenic LBP. Painful discs are characterized by a confluence of innervation, inflammation, and mechanical hypermobility. These three possible mechanisms are discussed in this review. Results Animal models and specimens from humans have revealed sensory innervation of lumbar IVDs and sensory nerve ingrowth into the inner layer of IVDs. Cytokines such as tumor necrosis factor-α and interleukins induce this ingrowth. Nerve growth factor has also been recently identified as an inducer of ingrowth. Finally, disc degeneration induces several collagenases; their action results in hypermobility and pain. Conclusions To treat discogenic LBP, it is important to prevent sensitization of sensory nerve fibers innervating the IVD, to suppress pathogenic increases of cytokines, and to decrease disc hypermobility.
Introduction: Many patients suffer from discogenic low back pain. However, the mechanisms, diagnosistic strategy, and treatment of discogenic low back pain all remain controversial. The purpose of ...this paper was to review the pathological mechanisms of discogenic low back pain.Methods: Many authors have investigated the pathological mechanisms of discogenic low back pain using animal models and examining human patients. Central to most investigations is understanding the innervation and instabilities of diseased intervertebral discs and the role of inflammatory mediators. We discuss three pathological mechanisms of discogenic low back pain: innervation, inflammation, and mechanical hypermobility of the intervertebral disc.Results: Sensory nerve fibers include C-fibers and A delta-fibers, which relay pain signals from the innervated outer layers of the intervertebral disc under normal conditions. However, ingrowth of these sensory nerve fibers into the inner layers of intervertebral disc occurs under disease conditions. Levels of neurotrophic factors and some cytokines are significantly higher in diseased discs than in normal discs. Stablization of the segmental hypermobility, which can be induced by intervertebral disc degeneration, suppresses inflammation and prevents sensitization of sensory nerve fibers innervating the disc.Conclusions: Pathological mechanisms of discogenic low back pain include sensory nerve ingrowth into inner layers of the intervertebral disc, upregulation of neurotrophic factors and cytokines, and instability. Inhibition of these mechanisms is important in the treatment of discogenic low back pain.
Purpose
Extreme lateral interbody fusion provides minimally invasive treatment of spinal deformity, but complications including nerve and psoas muscle injury have been noted. To avoid nerve injury, ...mini-open anterior retroperitoneal lumbar interbody fusion methods using an approach between the aorta and psoas, such as oblique lumbar interbody fusion (OLIF) have been applied. OLIF with percutaneous pedicle screws without posterior decompression can indirectly decompress the spinal canal in lumbar degenerated spondylolisthesis. In the current study, we examined the radiographic and clinical efficacy of OLIF for lumbar degenerated spondylolisthesis.
Methods
We assessed 20 patients with lumbar degenerated spondylolisthesis who underwent OLIF and percutaneous pedicle screw fixation without posterior laminectomy. MR and CT images and clinical symptoms were evaluated before and 6 months after surgery. Cross sections of the spinal canal were evaluated with MRI, and disk height, cross-sectional areas of intervertebral foramina, and degree of upper vertebral slip were evaluated with CT. Clinical symptoms including low back pain, leg pain, and lower extremity numbness were evaluated using a visual analog scale and the Oswestry Disability Index before and 6 months after surgery.
Results
After surgery, significant increases in axial and sagittal spinal canal diameter (12 and 32 %), spinal canal area (19 %), disk height (61 %), and intervertebral foramen areas (21 % on the right side, 39 % on the left), and significant decrease of upper vertebral slip (−9 %) were found (
P
< 0.05). Low back pain, leg pain, and lower extremity numbness were significantly reduced compared with before surgery (
P
< 0.05).
Conclusions
Significant improvements in disk height and spinal canal area were found after surgery. Bulging of disks was reduced through correction, and stretching the yellow ligament may have decompressed the spinal canal. Lumbar anterolateral fusion without laminectomy may be useful for lumbar spondylolisthesis with back and leg symptoms.
Abstract
Cervical ossification of the posterior longitudinal ligament (OPLL) is a contributing factor to spinal cord injury or trauma-induced myelopathy in the elderly. To reduce the incidence of ...these traumas, it is essential to diagnose OPLL at an early stage and to educate patients how to prevent falls. We thus evaluated the ability of our convolutional neural network (CNN) to differentially diagnose cervical spondylosis and cervical OPLL. We enrolled 250 patients with cervical spondylosis, 250 patients with cervical OPLL, and 180 radiographically normal controls. We evaluated the ability of our CNN model to distinguish cervical spondylosis, cervical OPLL, and controls, and the diagnostic accuracy was compared to that of 5 board-certified spine surgeons. The accuracy, average recall, precision, and F1 score of the CNN for classification of lateral cervical spine radiographs were 0.86, 0.86, 0.87, and 0.87, respectively. The accuracy was higher for CNN compared to any expert spine surgeon, and was statistically equal to 4 of the 5 experts and significantly higher than that of 1 expert. We demonstrated that the performance of the CNN was equal or superior to that of spine surgeons.
Introduction
The significance of the relationship between the spine and hip joints has been frequently discussed. However, the relationship between acetabular coverage and spinal sagittal alignment ...has not been fully elucidated as previous studies did not adequately control for factors that might affect the spinopelvic alignment. The aim of this study was to elucidate the impact of acetabular coverage on spinal sagittal alignment by comparing patient groups matched on sex, age, and the presence of hip and anterior impingement pain.
Materials and methods
We prospectively enrolled 30 women undergoing periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH) and 30 women undergoing hip arthroscopic surgery (HAS) for labral tears. The lateral centre edge angle was measured on hip radiographs. In addition, the sagittal vertical axis, pelvic tilt, pelvic incidence, sacral slope (SS), and lumbar lordosis (LL) were measured on preoperative plain radiographs of the whole spine to assess the sagittal spinal alignment. Clinical and radiologic data were compared between the two groups (PAO vs. HAS).
Results
The patient groups did not differ in age and body mass index. The mean SS was significantly greater in the PAO group (41.6° ± 1.6°) than in the HAS group (35.3° ± 1.5°;
P
= 0.0039). Additionally, the mean LL was significantly greater in the PAO group (54.5° ± 2.0°) than in the HAS group (45.1° ± 1.9°;
P
= 0.0015).
Conclusions
The SS and LL were greater in patients with DDH than in patients with hip pain, but without DDH. Patients with DDH might show lumbar hyperlordosis to rotate the pelvis anteriorly, increasing the anterosuperior acetabular coverage.
Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their ...derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease.
Research suggests that vascular endothelial growth factor (VEGF) levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively correlated with KOA severity. The relationship ...between synovial VEGF levels and pain in human KOA patients is not fully understood, and the role of VEGF in the pain pathway remains unclear.
We harvested synovial membrane (SM) from 102 patients with radiographic evidence of KOA (unilateral Kellgren/Lawrence K/L grade 2-4) during total knee arthroplasty. Patients scored their pain on a 0 to 10 cm visual analog scale (VAS). VEGF levels in the SM of KOA patients with strong/severe (VAS ≥ 6) and mild/moderate pain (VAS < 6) were compared. Correlations between VAS and VEGF mRNA expression were investigated. To investigate a possible mechanism for VEGF-induced pain, the distribution of VEGF and the neuropeptide apelin was determined by immunohistochemical analyses. To investigate the role of VEGF in regulating apelin expression, SM cells were exposed to VEGF.
VEGF expression in the VAS ≥ 6 group was significantly greater than expression in the VAS < 6 group. Expression levels of VEGF were also positively correlated with VAS. VEGF-positive cells were identified in the lining of the SM. Expression of apelin mRNA and protein were significantly elevated in SM cells treated with exogenous VEGF compared to those treated with vehicle.
Synovial VEGF may be involved in pain pathways in KOA and its action may be mediated by apelin.
We investigated the relationship between trunk muscle mass and spinal pathologies by gender. This multicenter cross-sectional study included patients aged ≥ 30 years who visited a spinal outpatient ...clinic. Trunk and appendicular muscle mass were measured using bioelectrical impedance analysis. The Oswestry Disability Index (ODI), visual analog scale (VAS) score for low back pain, sagittal vertical axis (SVA), and EuroQol 5 Dimension (EQ5D) score were investigated to evaluate spinal pathology. The association between trunk muscle mass and these parameters was analyzed by gender using a non-linear regression model adjusted for patients' demographics. We investigated the association between age and trunk muscle mass. We included 781 men and 957 women. Trunk muscle mass differed significantly between men and women, although it decreased with age after age 70 in both genders. Lower trunk muscle mass was significantly associated with ODI, SVA, and EQ5D score deterioration in both genders; its association with VAS was significant only in men. Most parameters deteriorated when trunk muscle mass was < 26 kg in men and < 19 kg in women. Lower trunk muscle mass was associated with lumbar disability, spinal imbalance, and poor quality of life in both genders, with significant difference in muscle mass.
Study design
A multicenter cross-sectional study.
Objectives
To clarify the relationship of trunk muscle mass with low back pain, spinal sagittal balance, and quality of life.
Summary of background ...data
Few reports have investigated the relationship of trunk muscle mass with lumbar spine function and spinal balance, and the clinical significance of trunk muscle mass remains unclear.
Methods
Patients attending spinal outpatient clinics at 10 different medical institutions were enrolled in this study. Patient demographics, trunk muscle mass and appendicular skeletal muscle mass (ASM) measured by bioelectrical impedance analysis (BIA), body mass index (BMI), Charlson Comorbidity Index (CCI), the Oswestry Disability Index (ODI), visual analog scale (VAS) for low back pain, sagittal vertical axis (SVA), and EuroQol 5 Dimension (EQ5D) score were investigated. Multivariate nonlinear regression analysis was used to investigate the association of trunk muscle mass with the ODI, VAS score, SVA, and EQ5D score.
Results
Of 2551 eligible patients, 1738 (mean age 70.2 ± 11.0 years; 781 men and 957 women) were enrolled. Trunk muscle mass was significantly correlated with the ODI, VAS score, SVA, and EQ5D score (
P
< 0.001) when adjusted for age, sex, BMI, ASM, CCI, and history of lumbar surgery. Patient deterioration was associated with a decrease in trunk muscle mass, and the deterioration accelerated from approximately 23 kg.
Conclusions
Trunk muscle mass was significantly associated with the ODI, VAS score, SVA, and EQ5D score. Trunk muscle mass may assume an important role to elucidate and treat lumbar spinal dysfunction and spinal imbalance.
Graphical abstract
These slides can be retrieved under Electronic Supplementary Material.
Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP). Following disc injury, nerve growth factor (NGF) concentrations rise in IVDs, and anti-NGF therapy has been shown to ...attenuate LBP in humans. Increased levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in degenerative IVDs and in in vitro studies suggest that these factors promote NGF production. However, whether these factors regulate NGF in vivo remains unclear. Thus, we studied NGF regulation in a mouse model of IVD injury.
After inducing IVD injury, we examined mRNA levels of Tnfa, Tgfb, and Ngf in IVDs from control and IVD-injured mice across 7 days. To do this, we used magnetic cell separation to isolate CD11b ( +) (macrophage-rich) and CD11b (-) (IVD cell-rich) cell fractions from injured IVDs. To study the effect of TNF-α on Ngf expression, we examined Ngf expression in injured IVDs from C57BL/6 J and Tnfa-knockout (KO) mice (C57BL/6 J background). To study the effect of TGF-β on Ngf expression, C57/BL6J mice were given an intraperitoneal injection of either the TGF-β inhibitor SB431542 or DMSO solution (vehicle) one and two days before harvesting IVDs.
mRNA expression of Tnfa, Tgfb, and Ngf was significantly increased in injured IVDs. Tnfa was predominantly expressed in the CD11b ( +) fraction, and Tgfb in the CD11b (-) fraction. Ngf expression was comparable between CD11b ( +) and CD11b (-) fractions, and between wild-type and Tnfa-KO mice at post-injury day (PID) 1, 3, and 7. SB431542 suppressed TGF-β-mediated Ngf expression and NGF production in vitro. Further, administration of SB431542 significantly reduced Ngf expression in IVDs such that levels were below those observed in vehicle-treated animals at PID3 and PID7.
A TGF-β inhibitor reduced Ngf expression in a mouse model of IVD injury, suggesting that TGF-β may regulate NGF expression in vivo.
PDF
