Search Results (92)

In the body, mast cells are found in the circulation and located in tissues. These immune cells arise in the bone marrow and are often associated with conditions such as allergies and asthma. However, these cells also play roles in other inflammatory reactions, dysregulated wound healing and chronic conditions. Regarding their presence in tissues of the intervertebral disc (IVD), mast cells have been located in the normal nucleus pulposus, and reports indicate mast cell numbers are elevated in IVD degenerative conditions. As the integrity of the IVD is reported to decline with ageing as well as in sciatica and clinically defined degenerative conditions, targeting mast cell function may be a viable conservative treatment option for the ageing IVD in health and disease. This review discusses the possible involvement of mast cells in IVD health and disease, and the rationale for the use of mast cell stabilizers such as ketotifen as potential treatment options for conditions affecting IVD integrity. Such mast cell targeting treatments may be considered alone or in combination with other molecules such as specific proteinase inhibitors impacting proteinases known to be present in the affected tissues, such as MMP-3 and HTRA1. Thus, a multicomponent approach in such treatments may provide effectiveness in inhibiting progressive loss of IVD integrity and function in chronic degenerative conditions or adverse outcomes due to non-resorption of extruded nucleus pulposus in sciatica. Full article

Lumbar intervertebral disc herniation is a common cause of low back and radicular leg pain, traditionally managed with a combination of conservative therapies and, when indicated, surgical discectomy. An intriguing phenomenon observed in many patients is the spontaneous resorption of herniated disc material over time, often correlating with significant symptom improvement. This article is presented as a narrative review synthesizing experimental, imaging, and clinical literature relevant to spontaneous disc resorption and its implications for clinical decision-making. This paper provides a comprehensive overview of spontaneous disc herniation resorption, exploring the underlying pathophysiological mechanisms and the factors that predict which herniations are likely to regress without surgery. Key mechanisms include inflammatory-mediated degradation of disc fragments, neovascularization with macrophage infiltration and phagocytosis of extruded nucleus pulposus tissue, and biological processes such as enzymatic matrix breakdown and cellular apoptosis that collectively lead to shrinkage of the herniated mass. Patient and disc characteristics that favour spontaneous resorption are identified, such as younger age, extruded or sequestered fragment type, larger initial herniation size, and robust inflammatory response on imaging, whereas certain chronic degenerative changes may reduce this likelihood. We also review current clinical guidelines and expert recommendations on when surgical intervention is warranted versus when conservative management and observation are appropriate. Understanding the probability of natural disc fragment resolution is critical in guiding treatment decisions. In the absence of severe neurological deficits or intractable pain, a period of non-operative management can often be pursued safely, given that the majority of patients experience substantial relief within a few months as discs regress. Conversely, timely surgery is advised for those with neurological compromise or refractory symptoms. By synthesizing the latest evidence on spontaneous disc herniation resorption and its predictors, this review aims to assist neurosurgeons and spine specialists in optimizing patient selection for conservative care and identifying the proper timing for surgical intervention to achieve the best clinical outcomes. Given the narrative design, conclusions are based on synthesis of heterogeneous evidence rather than formal comparative analysis. Full article

Background: Intervertebral disc degeneration is a prevalent condition and a major risk factor for disc herniation. Mechanical overload, aging, injury, and disease contribute to the annulus fibrosus’ structural failure, which allows nucleus pulposus material to escape and reduces the capacity to absorb shock. This study builds on previous investigations by evaluating additional thermoplastic polyurethane (TPU) filaments as potential materials for additively manufactured intervertebral disc replacements. Materials and Methods: Disc-shaped specimens (Ø50 × 10 mm) were fabricated using fused deposition modeling (FDM). A gyroid infill structure was employed with unit cell sizes ranging from 4 to 10 mm³ and wall thicknesses between 0.5 and 1.0 mm. The outer wall thickness varied from 0.4 to 0.8 mm. Four TPU filaments (Extrudr FlexSemiSoft, GEEE-TECH TPU, SUNLU TPU, and OVERTURE TPU) were tested, resulting in 36 parameter combinations per filament. Printed discs were examined via stereomicroscopy. Tensile testing was conducted according to DIN EN ISO 527-1 using Type 5A specimens. Mechanical performance under physiological loading was assessed through uniaxial compression tests, in which samples were compressed to 50% of their height while force–deformation curves were recorded. Target forces were defined as 4000–7500 N to maintain comparability with prior studies. Results: Across all filaments, a maximum of three parameter combinations per material achieved forces within the target range. Microscopy confirmed the dimensional accuracy of wall thicknesses with minimal deviation. Tensile strength values for GEEE-TECH, SUNLU, and FlexSemiSoft were comparable (10–11 MPa), while OVERTURE showed significantly lower strength (approximately 9 MPa). Tensile modulus values followed a similar trend: 25–30 MPa for three filaments and 17.5 MPa for OVERTURE. Conclusions: All four TPU filaments could be used to fabricate discs that met the mechanical requirements for compression. These results confirm that both the tested TPU materials and gyroid structures are suitable for potential intervertebral disc replacement applications. Full article

Intervertebral disc (IVD) herniation is a complex and multifactorial condition with a challenging diagnosis and limited therapeutic options, highlighting the need for reliable biomarkers to improve clinical decision-making. The aim of this study was to identify circulating prognostic biomarkers of IVD herniation regression. The plasma proteomic profile and the expression of circulating non-coding RNAs were analysed in a rat model of IVD herniation and were correlated with herniation size. Four candidate proteins (TNC, COPS3, JUP, and GNAI2) were significantly correlated with herniation size, with TNC further validated by ELISA. Additionally, miR-143-3p, miR-10b-5p, miR-27a-3p, miR-140-5p, miR-155-5p, miR-146a-5p, and miR-21-5p were positively correlated with herniation size. Moreover, TNC, COPS3, JUP, and GNAI2 were found to be potential targets of miR-155-5p. This study provides the first combined proteomic and miRNA account of preclinical plasma biomarkers of IVD herniation size, where TNC-miR-155-5p emerge as promising elements of a regulatory module with IVD herniation prognostic potential. Full article

Oxygen–ozone (O₂–O₃) therapy is widely used for treating lumbar disc herniation. However, controversy remains regarding the safest and most effective route of administration. While intradiscal injection is purported to show clinical efficacy, it has also been associated with serious complications. In contrast, the intramuscular route can exhibit a more favourable safety profile and comparable pain outcomes, suggesting its potential as a safer alternative in selected patient populations. This mixed-method study combined computed tomography (CT) imaging, biophysical diffusion modelling, and a meta-analysis of clinical trials to evaluate whether intramuscular O₂–O₃ therapy can achieve disc penetration and therapeutic efficacy comparable to intradiscal nucleolysis, while minimizing procedural risk. Literature searches across PubMed, Scopus, and Cochrane databases identified seven eligible studies (four randomized controlled trials and three cohort studies), encompassing a total of 120 patients. Statistical analyses included Hedges’ g, odds ratios, and number needed to harm (NNH). CT imaging demonstrated gas migration into the intervertebral disc within minutes after intramuscular injection, confirming the plausibility of diffusion through annular micro-fissures. The meta-analysis revealed substantial pain reduction with intramuscular therapy (Hedges’ g = −1.55) and very high efficacy with intradiscal treatment (g = 2.87), though the latter was associated with significantly greater heterogeneity and higher complication rates. The relative risk of severe adverse events was 6.57 times higher for intradiscal procedures (NNH ≈ 1180). O₂–O₃ therapy offers a biologically plausible, safer, and effective alternative to intradiscal injection, supporting its adoption as a first-line, minimally invasive strategy for managing lumbar disc herniation. Full article

Accurate labeling of intervertebral discs (IVDs) in MRI scans is crucial for diagnosing spinal-related diseases such as osteoporosis, vertebral fractures, and IVD herniation. However, automatic IVD labeling remains challenging. The main issues include visual similarity to surrounding bone, anatomical variation across individuals, and inconsistencies between MRI scans. Traditional post-detection disc labeling methods often struggle when localization algorithms miss discs or generate false positives. To address these challenges, we propose MSA-Net, a novel multi-scale attention network designed for semantic IVD labeling, emphasizing the use of prior geometric data. MSA-Net efficiently extracts multi-scale features and models intricate spatial dependencies throughout the spinal structure. We also integrate contrastive learning to enforce feature consistency. This helps the network distinguish IVDs from surrounding tissues. Extensive experiments on multi-center spine datasets demonstrate that MSA-Net consistently outperforms previous methods across MRI T1w and T2w modalities. These improvements demonstrate MSA-Net’s ability to handle variability in disc geometry, tissue contrast, and missed detections that challenge prior methods. Full article

Background and Objectives: Preoperative cefazolin is the standard of care for intervertebral disc surgery as it reduces the incidence of iatrogenic spondylodiscitis. The aim of this study was to determine the impact of intervertebral disc degeneration and endplate changes on the penetration of prophylactic cefazolin into the intervertebral disc during spinal surgery. Materials and Methods: Adult patients undergoing single-level microdiscectomy for lumbar disc herniation received prophylaxis with 2 g of cefazolin. Venous blood and intervertebral disc samples were collected and analyzed using high-performance liquid chromatography to determine cefazolin concentrations. The severity of intervertebral disc and endplate changes was assessed on magnetic resonance images using the Pfirrmann and Modic grading systems. Results: Cefazolin concentrations were significantly higher in cases with Modic type II changes compared to type 0/I (14.6 ± 9.2 µg g⁻¹ vs. 10.2 ± 4.5 µg g⁻¹ and 9.2 ± 4.1 µg g⁻¹; p = 0.01). 35.4% of patients with Modic type II changes had concentrations > 16 µg g⁻¹, compared to 10% and 25% for patients with Modic type 0/I (p = 0.008). For Pfirrmann grading, 34.6% of grade V discs reached >16 µg g⁻¹ versus 16.7% and 20.3% for grades III and IV (p = 0.26). Patient age, weight, and timing showed no significant correlations with intradisc concentrations. Conclusions: Ninety-four percent of disc samples exceeded the minimum inhibitory concentration for Staphylococcus aureus (>4 µg/g), but considerable variability in cefazolin levels was observed, with higher concentrations in discs showing Modic type II changes. Full article

This study aimed to evaluate the effects of acupuncture–moxibustion (AM) combined with Locomotor Training (LT) on functional recovery after surgery for Cervical Intervertebral Disc Herniation (IVDH) in dogs. Seventy-nine dogs undergoing ventral slot decompression (VSD) between 2022 and 2025 were enrolled and assigned to either the AM plus LT group (ALRG group) or the LT-only group (LRG group) based on postoperative rehabilitation protocols. To control for bias, post hoc analysis used propensity score matching (PSM) stratified by Rusbridge Grade. Primary outcomes included time to standing and walking recovery, along with Olby scores at five postoperative time points. Secondary endpoints included postoperative analgesic usage rate and duration, as well as long-term prognosis at 6–8 months postoperatively. After PSM, each group comprised 20 dogs. Compared with the LRG group, the ALRG group demonstrated shorter time to standing and walking recovery, better Olby score improvement, and significantly reduced opioid usage duration. Long-term follow-up revealed a higher complete success rate in the ALRG group. All trends were more pronounced in severe cases classified as Rusbridge grades 3 and 4. This study demonstrates the clinical feasibility of combining AM with LT rehabilitation for postoperative recovery in dogs with cervical IVDH. It provided new evidence for optimizing postoperative rehabilitation protocols and supports future large-scale prospective studies. Full article

This study evaluated serum neurofilament light chain (NfL) as a biomarker for spinal cord diseases in dogs, including 46 healthy dogs and 76 with conditions, such as intervertebral disc herniation (IVDH), syringomyelia (SM), fibrocartilaginous embolism (FCE), and acute non-compressive nucleus pulposus extrusion (ANNPE). There was a significant difference in serum NfL levels between healthy dogs (12.55 pg/mL) and those with spinal cord diseases (91.10 pg/mL; p < 0.0001). The NfL level in dogs with SM (50.7 pg/mL) was significantly lower than that in dogs with IVDH (99.3 pg/mL; p = 0.012) and those with other diseases, including FCE and ANNPE (241.0 pg/mL; p = 0.002). The area under the curve for differentiating between dogs with spinal cord diseases and healthy dogs was 0.91, with an optimal NfL cutoff value of 30.31 pg/mL (sensitivity of 80.68%; specificity of 91.30%). For dogs with IVDH treated solely with medication, the serum NfL levels in the Poor and Static group (180.0 pg/mL) were significantly higher than those in the Partial and Good group (81.30 pg/mL) (p = 0.03). Serum NfL is a promising biomarker for neuroaxonal injury, aiding in differentiating SM from other spinal cord diseases and evaluating treatment response. Full article

Degenerative disc disease (DDD) is a major cause of chronic low back pain (LBP), yet the molecular mechanisms driving disc degeneration and pain remain poorly understood. This study analyzed intervertebral disc (IVD) tissue from 36 young patients (median age = 36.00 [31.00, 42.50] years) with herniated discs and LBP, alongside healthy controls, to investigate changes in the extracellular matrix (ECM) and neurochemical alterations. Disc degeneration was assessed using MRI (Pfirrmann grading) and histology (Sive’s criteria). Histochemical and immunohistochemical methods were used to evaluate aggrecan content, calcification, and the expression of nerve growth factor (NGF), substance P (SP), and S-100 protein. MRI findings included Pfirrmann grades V (30.55%), IV (61.11%), III (5.56%), and II (2.78%). Severe histological degeneration (10–12 points) was observed in three patients. Aggrecan depletion correlated with longer pain duration (r = 0.449, p = 0.031). NGF expression was significantly elevated in degenerated discs (p = 0.0287) and strongly correlated with SP (r = 0.785, p = 5.268 × 10⁻⁹). Free nerve endings were identified in 5 cases. ECM calcification, present in 36.1% of patients, was significantly associated with radiculopathy (r = 0.664, p = 0.005). The observed co-localization of NGF and SP suggests a synergistic role in pain development. These results indicate that in young individuals, aggrecan loss, neurochemical imbalance, and ECM calcification are key contributors to DDD and chronic LBP. Full article

Background/Objectives: Lateral lumbar interbody fusion (LLIF) has gained popularity as an effective technique for indirect decompression through ligamentotaxis. Despite the perceived importance of using appropriately sized cages for achieving optimal decompression, comprehensive reports on cage size and its impact on indirect decompression are limited. This study aimed to assess the ligamentotaxis effect by measuring the “backward bulging” length in pre- and postoperative MRIs and examining its correlation with cage size and subsidence. Methods: T2 images of 270 patients with lumbar herniated disc and/or lumbar spondylolisthesis (June 2022 to March 2025) were analyzed for 530 intervertebral spaces. Data on gender, age, length of hospital stay, preoperative and postoperative lumbar JOA scores, and the level of the disease were collected. Measurements included backward bulging length, intervertebral height, and cage subsidence. Statistical analysis was performed using StatMate. Surgical procedures involved oblique lateral interbody fusion (OLIF) to minimize impact on the iliopsoas and lumbar plexus. Trial cages starting from 8 mm were sequentially inserted, with confirmation through lateral fluoroscopy. Posterior fixation was performed using percutaneous pedicle screws. Results: Analysis of 530 intervertebral spaces revealed that 70% could accommodate a cage 3 mm or larger than the preoperative intervertebral height. Significant backward bulging shortening (3 mm or more) occurred in 339 spaces, predominantly with larger cages. Only 8.8% of cases (14/159) with a large backward bulging shortening had an intervertebral height extension of 3 mm or less. On the other hand, a large reduction in backward bulging was observed in 91.3% of cases (339/371) with an intervertebral height extension of 3 mm or more. Postoperative cage subsidence was observed in 9.2% (49/530) of all intervertebral spaces and 8.6% (32/371) in spaces where a cage larger than 3 mm was used. There was no statistically significant difference between these two groups. Conclusions: To achieve a sufficient ligamentotaxis effect, it is necessary to select a cage size that allows for an intervertebral height increase of at least 3 mm compared to the preoperative measurement. Full article

Background/Objectives: Lumbar disc herniation (LDH) is the most common condition associated with low back pain, and it adversely impacts individuals’ health. The interplay between energy metabolism and apoptosis is critical, as the loss of viable cells in the intervertebral disc (IVD) can lead to a cascade of degenerative changes. Efferocytosis is a key biological process that maintains homeostasis by removing apoptotic cells, resolving inflammation, and promoting tissue repair. Therefore, enhancing mitochondrial energy metabolism and efferocytosis function in IVD cells holds great promise as a potential therapeutic approach for LDH. Methods: In this study, energy metabolism and efferocytosis-related differentially expressed genes (EMERDEGs) were identified from the transcriptomic datasets of LDH. Machine learning approaches were used to identify key genes. Functional enrichment analyses were performed to elucidate the biological roles of these genes. The functions of the hub genes were validated by RT-qPCR. The CIBERSORT algorithm was used to compare immune infiltration between LDH and Control groups. Additionally, we used single-cell RNA sequencing dataset to analyze cell-specific expression of the hub genes. Results: By using bioinformatics methods, we identified six EMERDEGs hub genes (IL6R, TNF, MAPK13, ELANE, PLAUR, ABCA1) and verified them using RT-qPCR. Functional enrichment analysis revealed that these genes were primarily associated with inflammatory response, chemokine production, and cellular energy metabolism. Further, we identified candidate drugs as potential treatments for LDH. Additionally, in immune infiltration analysis, the abundance of activated dendritic cells, neutrophils, and gamma delta T cells varied significantly between the LDH group and Control group. The scRNA-seq analysis showed that these hub genes were mainly expressed in chondrocyte-like cells. Conclusions: The identified EMERDEG hub genes and pathways offer novel insights into the molecular mechanisms underlying LDH and suggest potential therapeutic targets. Full article

Background/Objectives: Canine intervertebral disc herniation (IVDH) is an important musculoskeletal pathology. Unlike in humans, IVDH mechanisms in dogs are underinvestigated from a system-level integrative omics point of view. The aim of this study was to identify key serum molecular players in canine IVDH. Methods: An integrative multi-omics approach combining high-resolution LC-MS-based untargeted metabolomics and tandem mass tag (TMT)-based proteomics was applied. Additionally, serum zinc concentration was determined by spectrophotometry. Results: Nineteen serum metabolites were differentially abundant in IVDH dogs. Metabolite analysis highlighted dysregulation in lipoic acid and branched-chain amino acid (BCAA) metabolism, with elevated levels of valine, leucine, and isoleucine in IVDH. These findings suggest disrupted energy, nitrogen, and neurotransmitter metabolism, potentially contributing to the IVDH pathophysiology. Additionally, lower serum uridine, possibly influenced by BCAA accumulation, was observed, indicating altered neuroinflammatory responses. ELISA validation confirmed elevated serum levels of zinc-α2-glycoprotein (ZAG), alpha-1-microglobulin/bikunin precursor (AMBP), and vitronectin (VTN) in IVDH, supporting immune modulation and neuroprotective mechanisms. Serum prekallikrein (KLKB1) and Protein C inhibitor (SERPINA5), involved in fibrin cloth formation, were found to be lowered in IVDH patients. Pathway enrichment revealed disturbances in aromatic amino acid biosynthesis, with elevated phenylalanine, tyrosine, and tryptophan influencing neurotransmission and inflammation. In addition, elevated serum Zn concentration emphasized its antioxidant importance in immune response, wound healing, and neuropathic pain signaling. Conclusions: Integration with our prior CSF multi-omics data reinforced the relevance of identified molecules in IVDH-associated neurodegeneration, inflammation, and repair processes. This study offers insight into potential diagnostic biomarkers and therapeutic targets for canine IVDH through serum-based molecular profiling. Full article

This study evaluated attenuation values of lumbar epaxial musculature in dogs with acute spinal pathology using computed tomography (CT) and compared them with values in dogs without spinal disease. Sixty client-owned dogs were included: thirty dogs with thoracolumbar spinal lesions (intervertebral disc herniation) and thirty control dogs without spinal abnormalities. Mean Hounsfield unit (HU) values of epaxial muscles (multifidus–longissimus–iliocostalis group) were measured bilaterally at three lumbar levels for each dog—one level cranial to the lesion, the lesion level, and one level caudal to the lesion; for controls, the corresponding segments were T13, L1, L2, and L3. Dogs with spinal pathology showed a significant local decrease in muscle HU at the lesion site (average ~48 HU) compared to the segment cranial to the lesion (~50–51 HU, p < 0.01). In contrast, control dogs had relatively uniform muscle HU (~52–54 HU) across T13–L3 with no significant differences between these levels. Side to side differences were minimal in both groups. A logistic regression using the HU drop between segments correctly classified ~70% of cases, indicating moderate diagnostic value. Age and breed influenced overall muscle HU; older dogs had lower values (r = –0.39, p = 0.03 in controls), and French Bulldogs showed lower HU than other breeds. In conclusion, dogs with acute thoracolumbar disc herniation exhibit a focal reduction in paraspinal muscle HU at the lesion level. This acute change is subtle but detectable with CT and may serve as an additional indicator of lesion presence or chronicity, although its clinical utility requires further investigation in larger studies. Full article

Spinal degenerative changes can predispose back pain and neurological deficits in dogs. In humans and veterinary patients, the endplate junction has been proposed as an alternative site of failure in addition to damage of the annulus fibrosus, leading to intervertebral disc herniation. Some alterations lead to contour abnormalities with or without regional mineralizations and can be classified as Endplate Junction Failure (EPJF), osteochondrosis (with or without fragmentation), or spondylarthritis. The objective of this retrospective study was to describe the prevalence of endplate junction alterations (EPJA) on CT in dogs at the cervicothoracic junction and classify alterations based on recent presumed EPJF grading. Computed tomographic scans of 315 dogs that included the cervicothoracic (C6–T2) spine for a variety of reasons obtained between January 2020 and December 2022 were assessed for the presence of alterations, location and type. Other spinal abnormalities were also described. A total of 945 intervertebral disc spaces were evaluated, and EPJA were found in 11 intervertebral disc spaces (1.16%). C6–C7 and C7–T1 intervertebral disc spaces were equally affected (five cases each), with only one case affecting T1–T2. In conclusion, cervicothoracic endplate alterations were anecdotically observed on CT in a population of dogs. Full article