Serum periostin levels correlate with severity of intervertebral disc degeneration.

PURPOSE: Periostin, an extracellular matrix protein closely related to mechanical stress, inflammation, and ageing, has been implicated in intervertebral disc degeneration (IVDD) in basic research. However, it has not been examined in clinical cases. This study aimed to evaluate the association between IVDD severity and serum periostin concentration as well as to analyse potential associations between IVDD and clinical and demographic factors. METHODS: This retrospective cohort study included 198 patients who underwent lumbar disc herniation and lumbar canal stenosis between January 2020 and December 2022. The severity of IVDD was evaluated using the Pfirrmann grading, whereas serum periostin levels were measured using ELISA kits. Clinical demographics, including age, sex, body mass index, comorbidities, psoas muscle index, and spinal disease, were also recorded. RESULTS: This study demonstrated a significant correlation between high serum periostin levels and IVDD severity, as indicated by a high cumulative Pfirrmann score. Serum periostin levels were identified as an independent risk factor for IVDD in a multivariate regression model. Correlation analysis showed a correlation between periostin levels and Pfirrmann grade at each lumbar level (ρ = 0.458-0.550, p < 0.001) and a strong correlation with cumulative Pfirrmann score (ρ = 0.690, p < 0.001). CONCLUSION: The higher the serum periostin level, the higher the cumulative Pfirrmann score. Multivariate analysis showed that serum periostin was an independent risk factor for IVDD. Periostin levels may be a clinically suitable and useful biomarker for diagnosing IVDD, estimating disease progression and activity, providing prognostic information, and evaluating treatment options.

Expressions of IL-12 and its receptors in patients with lumbar disc herniation and their relationship with clinical efficacy.

This study aimed to explore the expressions of interleukin-12 (IL-12) and its receptors IL-23R and IL12RB2 in patients with lumbar disc herniation (LDH) before and after treatment and their relationship with clinical efficacy. A total of 172 LDH patients undergoing surgical treatment in Wuhan Third Hospital, Tongren Hospital of Wuhan University were enrolled as the study group, and 170 healthy subjects as the control group. 5 mL of fasting venous blood was taken before surgery (T0), 1 d (T1), 3 d (T2), 5 d (T3) and 7 d (T4) after treatment respectively. The concentrations of IL-12, IL-23R and IL12RB2 in the two groups were detected, and the correlation between them and the treatment duration and clinical efficacy was analyzed. The study group showed significantly higher serum IL-12, IL-23R and IL12RB2 than the control group before treatment (P < 0.001). In the study group, IL-12, IL-23R and IL-12RB2 were the lowest at T4 (P < 0.001), followed by T3 (P < 0.001). There was no significant difference in IL-23R at T1 and T0 (P > 0.050), and in IL12RB2 at T1 and T2 (P > 0.050). Spearman rank correlation showed that IL-12, IL-23R, IL12RB2 were negatively correlated with treatment duration in the study group (P < 0.001), and were positively correlated with clinical efficacy (P < 0.001). In conclusion, the concentrations of serum IL-12, IL-23R and IL12RB2 in LDH patients are significantly higher than those in normal controls. Moreover, the concentrations are closely related to the rehabilitation of patients and are expected to become therapeutic targets for LDH.

LncRNA MAGI2-AS3 is down-regulated in intervertebral disc degeneration and participates in the regulation of FasL expression in nucleus pulposus cells.

BACKGROUND: It is known that Fas ligand (FasL) is involved in the development of intervertebral disc degeneration (IDD). A recent study reported that lncRNA MAGI2-AS3 up-regulated the expression of FasL to promote breast cancer. Therefore, we investigated the roles that lncRNA MAGI2-AS3 might play in IDD. METHODS: A total of 66 IDD patients (IDD group) and 58 healthy volunteers (Control group) were recruited in this study. Quantitative real-time PCR (qRT-PCR) and western blot were used to investigate gene expression levels. Cell transfections were carried out to analyze gene interactions. The diagnostic value of lncRNA MAGI2-AS3 for IDD was assessed by ROC curve analysis. RESULTS: The expression levels of plasma lncRNA MAGI2-AS3 were lower in IDD patients compared to that in the control group. Down-regulation of lncRNA MAGI2-AS3 effectively distinguished IDD patients from the control group. The expression levels of plasma lncRNA MAGI2-AS3 were significantly increased after the treatments. Over-expression of lncRNA MAGI2-AS3 inhibited the expression of FasL, while the silencing of lncRNA MAGI2-AS3 promoted the expression of FasL in nucleus pulposus (NP) cells. CONCLUSIONS: Therefore, lncRNA MAGI2-AS3 is down-regulated in IDD and participates in the regulation of FasL expression in nucleus pulposus (NP) cells.

Intervertebral disc degeneration in mice with type II diabetes induced by leptin receptor deficiency.

BACKGROUND: The leptin receptor-deficient knockout (db/db) mouse is a well-established model for studying type II diabetes mellitus (T2DM). T2DM is an important risk factor of intervertebral disc degeneration (IVDD). Although the relationship between type I diabetes and IVDD has been reported by many studies, few studies have reported the effects of T2DM on IVDD in db/db mice model. METHODS: Mice were separated into 3 groups: wild-type (WT), db/db, and IGF-1 groups (leptin receptor-deficient mice were treated with insulin-like growth factor-1 (IGF-1). To observe the effects of T2DM and glucose-lowering treatment on IVDD, IGF-1 injection was used. The IVD phenotype was detected by H&E and safranin O fast green staining among db/db, WT and IGF-1 mice. The levels of blood glucose and weight in mice were also recorded. The changes in the mass of the trabecular bone in the fifth lumbar vertebra were documented by micro-computed tomography (micro-CT). Tunnel assays were used to detect cell apoptosis in each group. RESULTS: The weight of the mice were 27.68 ± 1.6 g in WT group, which was less than 57.56 ± 4.8 g in db/db group, and 52.17 ± 3.7 g in IGF-1 injected group (P < 0.05). The blood glucose levels were also significantly higher in the db/db mice group. T2DM caused by leptin receptor knockout showed an association with significantly decreased vertebral bone mass and increased IVDD when compared to WT mice. The db/db mice induced by leptin deletion showed a higher percentage of MMP3 expression as well as cell apoptosis in IVDD mice than WT mice (P < 0.05), while IGF-1 treatment reversed this situation (P < 0.05). CONCLUSIONS: T2DM induced by leptin receptor knockout led to IVDD by increasing the levels of MMP3 and promoting cell apoptosis. IGF-1 treatment partially rescue the phenotype of IVDD induced by leptin receptor knockout.

The expression of cytokine and its significance for the intervertebral disks of Kazakhs.

BACKGROUND: Proinflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 are expressed in herniated intervertebral disks of Kazakhs, but their significance is not yet understood. METHODS: Specimens of herniated lumbar disk were collected from 30 patients with single disk herniation during lumbar discectomy. As a control, 10 specimens were collected postmortem from the cadavers of individuals who did not die from spinal disease. The clinical symptoms in all cases were evaluated preoperation by the JOA index. The expressions of IL-6 and IL-10 in the degenerative disk cells of each specimen were detected using immunohistochemical staining. The amounts of IL-6 and IL-10 in each intervertebral disk were assessed by enzyme-linked immunosorbent assay. RESULTS: The expression levels of IL-6 and IL-10 were significantly higher in the patient group than in the control group. Statistical analysis showed differences between ethnic Kazakh and Han patients in both the expression of IL-6 and JOA scores. Immunohistochemical staining showed that in the patient group, IL-6 was found in 28 patients and IL-10 was found in 27 patients. CONCLUSION: The high expression of cytokines, such as IL-6 and IL-10, has an important relationship with disk degeneration. Of course, age is another factor in cell apoptosis of degenerative disks. More research is necessary to discover how ethnicity and heredity impact the levels of expressed cytokines.

Systemic blood plasma CCL5 and CXCL6: Potential biomarkers for human lumbar disc degeneration.

Lumbar disc degeneration severity on magnetic resonance imaging (MRI) is associated with low back pain. Pro-inflammatory chemokines CCL5 and CXCL6 are released by induced degenerative discs, and CCL5 has been associated with discogenic back pain. A case-control study was performed, based on the Hong Kong Disc Degeneration Population-Based Cohort of Southern Chinese, to investigate if systemic levels of CCL5 and CXCL6 were elevated in subjects with disc degeneration compared to non-degenerated individuals. Eighty subjects were selected, 40 with no disc degeneration (control group; DDD score 0) and 40 with moderate/severe disc degeneration (disc degeneration group; DDD score ≥5) as noted on MRI. Subjects were matched for age, sex, body mass index and workload. Blood plasma samples were obtained from each individual, and levels of CCL5 and CXCL6 were measured. Secondary phenotypes of lumbar disc displacement and cervical disc changes were also assessed. CCL5 concentrations were significantly increased in the disc degeneration (mean: 19.8 ng/mL) compared to the control group (mean: 12.8 ng/mL) (p = 0.015). The degeneration group demonstrated higher levels of CXCL6 (mean: 56.9 pg/mL) compared to the control group (mean: 43.4 pg/mL) (p = 0.010). There was a trend towards elevated CCL5 levels with disc displacement in the degeneration group (p = 0.073). Cervical disc degeneration was not associated with elevated chemokine levels (p > 0.05). This is the first study to note that elevated systemic CCL5 and CXCL6 were associated with moderate/severe lumbar disc degeneration, further corroborating tissue studies of painful discs. These chemokines may be systemic biomarkers for the diagnosis and monitoring of disc degeneration.

Inflammatory profiles in canine intervertebral disc degeneration.

BACKGROUND: Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE2), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs. RESULTS: PGE2 levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples. CONCLUSIONS: PGE2 levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the AF increased with advancing degeneration stages. Although macrophages invaded the AF as degeneration progressed, the production of inflammatory mediators seemed most pronounced in degenerated NP tissue. Future studies are needed to investigate if inhibition of PGE2 levels in degenerated IVDs provides effective analgesia and exerts a protective role in the process of IVD degeneration and the development of IVD disease.

Evaluation of serum phosphorylated neurofilament subunit NF-H as a prognostic biomarker in dogs with thoracolumbar intervertebral disc herniation.

OBJECTIVE: To investigate whether pNF-H is a prognostic biomarker of spinal cord injury (SCI) in paraplegic dogs with thoracolumbar intervertebral disc herniation (IVDH). STUDY DESIGN: Prospective, case-control clinical study ANIMALS: Dogs (n = 60) with SCI from IVDH and 6 healthy dogs. METHODS: Serum from 60 thoracolumbar IVDH dogs (Grade 4: 22 dogs; Grade 5: 38 dogs) collected 1-3 days after injury, and 6 control dogs, was analyzed using enzyme-linked immunosorbent assay (ELISA) against a phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H). Serum pNF-H levels were compared between different IVDH grades and their prognostic value was investigated. RESULTS: pNF-H levels were significantly greater in Grade 5 than Grade 4 dogs. There were significant differences in pNF-H levels between dogs that regained voluntarily ambulation and those that did not. All 8 dogs that had high pNF-H levels 1-3 days after injury did not regain the ability to walk after surgery. CONCLUSIONS: Serum pNF-H levels might be a biomarker for predicting prognosis of canine SCI.

Evidence of MRI image features and inflammatory biomarkers association with low back pain in patients with lumbar disc herniation.

BACKGROUND CONTEXT: While MRI image features and inflammatory biomarkers are frequently used for guiding treatment decisions in patients with lumbar disc herniation (LDH) and low back pain (LBP), our understanding of the connections between these features and LBP remains incomplete. There is a growing interest in the potential significance of MRI image features and inflammatory biomarkers, both for quantification and as emerging therapeutic tools for LBP. PURPOSE: To investigate the evidence supporting MRI image features and inflammatory biomarkers as predictors of LBP and to determine their relationship with pain intensity. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: All consecutive patients with LDH who underwent discectomy surgery at our institution from February 2020 to June 2023 at the author's institution were included. OUTCOME MEASURES: MRI image features in discogenic, osseous, facetogenic, and paraspinal muscles, as well as inflammatory biomarkers in serum (including CRP (C-reactive protein), ESR (erythrocyte sedimentation rate), PCT (procalcitonin), TNF (tumor necrosis factor), interleukin-1 beta (IL-1ß), and IL-6), and paraspinal muscles (including TNF, IL-1ß, IL-6, IL-10, and transforming growth factor beta 1 (TGF-ß1)). METHODS: A series of continuous patients diagnosed with LDH were categorized into acute LBP (<12 weeks), chronic LBP (≥12 weeks), and nonLBP groups. MRI image features and inflammatory biomarkers relation to pain intensity was assessed using the independent t-test, Chi-squared tests, Spearman rank correlation coefficient, and logistic regression test. RESULTS: Compared to the nonLBP group, the chronic LBP group exhibited a higher incidence of intervertebral disc (IVD) degeneration (≥ grade 3) and high-fat infiltration in paraspinal muscles, alongside a significant reduction in the cross-sectional area (CSA) and fatty degeneration of the multifidus muscle. Furthermore, there was a greater expression of IL-6 in serum and TNF in paraspinal muscles in the chronic LBP group and a greater expression of CRP and IL-6 in serum and TNF in paraspinal muscles in the acute LBP group. CSA and fatty degeneration of multifidus muscle were moderately negatively correlated with chronic LBP scores. The expression of TNF and IL-6 in serum and the expression of TNF in the multifidus muscle were moderately correlated with preoperative LBP. IVD degeneration and high-fat infiltration were identified as risk factors for chronic LBP. CONCLUSION: The results provide evidence that IVD degeneration, high-fat infiltration, and the reduction of CSA in paraspinal muscles were associated with the development of chronic LBP in patients with LDH, and these associations are linked to inflammatory regulation. This deepens our understanding of the etiology and pathophysiology of LBP, potentially leading to improved patient stratification and more targeted interventions.

Identification of Characteristic Genes in Whole Blood of Intervertebral Disc Degeneration Patients by Weighted Gene Coexpression Network Analysis (WGCNA).

Intervertebral disc degeneration (IDD) is a major cause of lower back pain. However, to date, the molecular mechanism of the IDD remains unclear. Gene expression profiles and clinical traits were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, weighted gene coexpression network analysis (WGCNA) was used to screen IDD-related genes. Moreover, least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine (SVM) algorithms were used to identify characteristic genes. Furthermore, we further investigated the immune landscape by the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm and the correlations between key characteristic genes and infiltrating immune cells. Finally, a competing endogenous RNA (ceRNA) network was established to show the regulatory mechanisms of characteristic genes. A total of 2458 genes were identified by WGCNA, and 48 of them were disordered. After overlapping the genes obtained by LASSO and SVM-RFE algorithms, genes including LINC01347, ASAP1-IT1, lnc-SEPT7L-1, B3GNT8, CHRNB3, CLEC4F, LOC102724000, SERINC2, and LOC102723649 were identified as characteristic genes of IDD. Moreover, differential analysis further identified ASAP1-IT1 and SERINC2 as key characteristic genes. Furthermore, we found that the expression of both ASAP1-IT1 and SERINC2 was related to the proportions of T cells gamma delta and Neutrophils. Finally, a ceRNA network was established to show the regulatory mechanisms of ASAP1-IT1 and SERINC2. In conclusion, the present study identified ASAP1-IT1 and SERINC2 as the key characteristic genes of IDD through integrative bioinformatic analyses, which may contribute to the diagnosis and treatment of IDD.

Increase in serum nerve growth factor but not intervertebral disc degeneration following whole-body vibration in rats.

BACKGROUND: Low back pain is a leading cause of disability and is frequently associated with whole-body vibration exposure in industrial workers and military personnel. While the pathophysiological mechanisms by which whole-body vibration causes low back pain have been studied in vivo, there is little data to inform low back pain diagnosis. Using a rat model of repetitive whole-body vibration followed by recovery, our objective was to determine the effects of vibration frequency on hind paw withdrawal threshold, circulating nerve growth factor concentration, and intervertebral disc degeneration. METHODS: Male Sprague-Dawley rats were vibrated for 30 min at an 8 Hz or 11 Hz frequency every other day for two weeks and then recovered (no vibration) for one week. Von Frey was used to determine hind paw mechanical sensitivity every two days. Serum nerve growth factor concentration was determined every four days. At the three-week endpoint, intervertebral discs were graded histologically for degeneration. FINDINGS: The nerve growth factor concentration increased threefold in the 8 Hz group and twofold in the 11 Hz group. The nerve growth factor concentration did not return to baseline by the end of the one-week recovery period for the 8 Hz group. Nerve growth factor serum concentration did not coincide with intervertebral disc degeneration, as no differences in degeneration were observed among groups. Mechanical sensitivity generally decreased over time for all groups, suggesting a habituation (desensitization) effect. INTERPRETATION: This study demonstrates the potential of nerve growth factor as a diagnostic biomarker for low back pain due to whole-body vibration.

Lower Plasma Melatonin in the Intervertebral Disk Degeneration Patients Was Associated with Increased Proinflammatory Cytokines.

BACKGROUND: Intervertebral disc degeneration (IDD) was considered to be the pathological basis of intervertebral disc herniation (IDH). However, the plasma melatonin in the IDD cases and healthy controls remained unclear. METHODS: In this case-control study, a total of 71 IDD cases and 54 healthy controls were enrolled between April 2020 and August 2020. The diagnostic effect of plasma melatonin for IDD was detected using receiver operating characteristic curve. The correlations between two continuous variables were detected with the Pearson linear analyses. RESULTS: It was found that lower melatonin concentration was detected in the IDD cases (1.906 ± 1.041 vs 3.072 ± 0.511 pg/mL, P<0.001). Through receiver operating characteristic curve analyses, it was found that plasma melatonin could be used as a diagnostic biomarker for IDD (area under curve=0.808, P<0.001). In advanced correlation analyses, it was found that plasma melatonin concentration was negatively associated with the age, symptom durations, IDD disease severity and proinflammatory factors, including IL-6 and TNF-α concentrations (P<0.05). Comparing with the higher melatonin groups, significantly increased IL-6 (0.601 ± 0.085 vs 0.507 ± 0.167 pg/mL, P=0.028) and TNF-α (3.022 ± 0.286 vs 2.353 ± 0.641, P<0.001) were detected in the patients with lower melatonin concentration. CONCLUSION: The plasma melatonin concentration was significantly decreased in the IDD cases and plasma melatonin could be used as a diagnostic biomarker for IDD. Lower plasma melatonin was associated with longer disease durations, elevated disease severity and higher inflammatory cytokines levels in IDD patients.

The Dual Effect of Abnormal Serum Uric Acid on Intervertebral Disc Degeneration.

An abnormal serum uric acid (SUA) level is associated with many diseases. To our knowledge, there is no research on the association between SUA and intervertebral disc degeneration (IDD). The purpose of this study was to determine the relationship between SUA and IDD. From June 2011 to July 2020, 691 patients undergoing surgery for lumbar disc herniation (LDH) were included in the LDH group, and 684 patients who underwent endoscopic surgery for knee trauma were included in the non-LDH group. We examined the baseline characteristics of all these patients and divided the SUA level into 10 groups according to the percentiles in males, females, and the total population. Subsequently, the relationship between the SUA level and IDD was further analyzed. There was no statistically significant difference in the baseline characteristics of the two groups (p > 0.05). Among the 10 groups, the LDH rate was higher at both lower and higher SUA levels. In multiple logistic regression analysis, after adjustment for age, sex, body mass index, smoking, and drinking, when the SUA level was <20% or >80%, compared with 60-80%, the odds ratio (OR) and 95% confidence interval (CI) of LDH of the total population were 1.821 (1.125-2.946) and 1.701 (1.186-2.438), respectively, and in the males, they were 1.922 (1.169-3.161) and 2.800 (1.766, 4.439), respectively. In females, when the SUA was <20%, there was a higher LDH rate (OR = 1.951, 95% CI 1.091-3.486). The present study suggests that there is a U-shaped relationship between SUA and IDD, being particularly prominent among male. Lower and higher SUA level may be risk factors for IDD.

Gene expression profiles of disc tissues and peripheral blood mononuclear cells from patients with degenerative discs.

The objective of this study was to analyze gene expression profiles of intervertebral disc samples and peripheral blood mononuclear cells (PBMCs) from patients with degenerative discs using Agilent's Human 1A Oligo microarray. RNA samples from disc tissue and PBMCs were obtained from patients with degenerative discs and from subjects in a control group. RNA samples were reverse-transcribed into Cy5-labeled cRNA, combined with a Cy3-labeled reference and hybridized to oligonucleotide microarrays. Microarrays were scanned by Gene-Pix 4000B and data were analyzed using GenePixPro 3.0 software. The microarray data were validated in the same RNA samples by qRT-PCR analysis of selected genes. For the disc tissue, the mRNA expressions of 522 genes changed obviously in the degeneration group, accounting for approximately 2.64% of all analyzed transcripts. These included transcription-related, ion channel and transport protein, receptor, protein synthesis and modifying, growth factor, etc. For PBMCs, the expressions of 62 genes changed obviously in the patients in the degeneration group. These changes included ion channel, transport protein, transcription-related, DNA synthesis and repair, metalloprotease, immune globulin-related, growth factor-related, extracellular matrix-related, adhesion molecule, etc. Analyzed on the association of the differential expression of genes between disc tissue and PBMCs, some genes were not compatible. The course of intervertebral disc denegation is a complicated dynamic process, however, and may mainly be local pathogenesis. These findings furnish new data for the mechanistic investigation of degenerative discs.

Relationship of lumbar disc degeneration with hemoglobin value and smoking.

BACKGROUND/OBJECTIVE: Although a number of studies report an important effect of smoking on disc degeneration and herniation, others did not identify such a relationship. The purpose of this study was to assess the relationship of lumbar disc degeneration with hemoglobin value and smoking. METHODS: The study included 200 adult patients who presented to the neurosurgery polyclinic with a complaint of back pain. Smoking habits were classified as "smoking for more than 10 years", "smoking for less than 10 years", and "not smoking". Lumbar disc degeneration was classified on modified Pfirrmann score according to lumbar MR images. Degeneration level was compared according to smoking group on Kruskal-Wallis test. The relationship between hemoglobin value and disc degeneration according to smoking group was assessed on the Spearman correlation coefficient. RESULTS: Disc degeneration values were significantly different between groups in L5-S1, L4-L5 and L3-L4 (P=0.018, P=0.012, P=0.038). Degeneration levels in L5-S1 in those who did not smoke were significantly lower than in those who smoked for both less and more than 10 years (P=0.048, P=0.022). No significant differences were found in degeneration level between those who smoked for more versus less than 10 years. For L3-L4 degeneration, there was a significant relationship with hemoglobin value in the group that did not smoke and in the group that smoked for more than 10 years (r=-0.395; P=0.009, r=0.329; P=0.018). CONCLUSION: This study found that, when risk factors such as systemic disease, heavy working conditions, obesity, trauma and family history were excluded, smoking increased lumbar disc degeneration. In addition, chronic smoking was found to increase hemoglobin values.

Time Course of Changes in Serum Oxidative Stress Markers to Predict Outcomes for Surgical Treatment of Lumbar Degenerative Disorders.

Recent reports indicate that oxidative stress is involved in the pathobiology of acute spinal cord injury or compression myelopathy. We conducted an observational study to determine levels of oxidative stress markers in serum from 80 patients who underwent spinal surgery to treat neurological symptoms related to lumbar degenerative disorders. Serum samples were collected before surgery and at 3 months, 6 months, and 1 year after surgery. Derivatives of reactive oxygen metabolites (ROM) in the serum samples were measured to gauge the level of oxidative stress. For preoperative neurological evaluation, patients were assessed for motor weakness in the lower extremities. We divided the patient samples into two groups: ROM decreasing at 1 year after surgery (G group) and ROM increasing at 1 year after surgery (W group). Then, we evaluated clinical outcomes using the visual analog scale and Oswestry disability index (ODI). Among the samples from the 80 enrolled patients, mean ROM levels before surgery increased to 388.5 ± 92.0, indicating the presence of moderate oxidative stress. The level of ROM gradually decreased after surgery and 1 year after surgery: the levels had significantly decreased to 367.6 ± 83.3 (p < 0.05). In patients who exhibited motor weakness, ROM values were significantly increased compared to those patients who had no motor weakness (p < 0.05). In analyses of clinical outcomes, ODI values for the W group 1 year after surgery were significantly higher than those for the G group (p < 0.05). Moderate oxidative stress was present in patients who had lumbar degenerative disorders and the degree of oxidative stress gradually improved within 1 year after surgery. The clinical results suggest that neurogenic oxidative stress can be mitigated by surgery for patients with lumbar degenerative disorders, and residual oxidative stress reflects poor surgical outcomes.

[Serum biomarkers in acute low back pain and sciatica]. / Szérumbiomarkerek akut lumbalis-lumbosacralis fájdalomban.

Inflammation contributes to the pathogenesis of low back pain and sciatica. Growing evidence suggests that elevated levels of some inflammatory biomarkers are associated with these conditions. Much of the research evaluating the association between pro- and anti-inflammatory cytokines, chemokines, other regulatory molecules, and low back pain and sciatica, focused on patients with chronic low back pain, while fewer studies addressed the issue of detectable biomarkers in the acute phase. Previous studies suggest that pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8 and anti-inflammatory IL-4 and IL-10 play an important role in the inflammatory response following intervertebral disc herniation. According to the approach of personalized medicine it is important to identify subsets of patients within the acute patient group regarding etiology, prognosis and treatment. In addition, if we can identify subgroups based on levels of pro-inflammatory biomarkers, where inflammation may be the leading cause of pain, we assume that this subgroup would likely be effectively treated with anti-inflammatory medication. The efficacy of TNF-α inhibitors and IL-6 inhibitors in treating low back pain and sciatica has already been tested in clinical trials, but further studies are required. Overall, identification of circulating biomarkers of acute low back pain and sciatica may assist in refining personalized diagnosis and treatment. Further research is needed to evaluate the role of inflammation in acute low back pain and sciatica, to identify what methods are appropriate for evaluation in clinical practice, and whether there are biomarkers of prognostic value in these patients. Orv Hetil. 2020; 161(13): 483-490.

Effect of subcutaneous needling on visual analogue scale, IgG and IgM in patients with lumbar disc herniation: Study protocol clinical trial (SPIRIT Compliant).

BACKGROUND: Lumbar disc herniation (LDH) is a disease commonly seen in clinical practice. In the majority of such patients presenting in clinic, the symptoms can be relieved or even abolished after non-surgical treatment. Floating needle therapy has attracted considerable attention as a promising non-surgical technique to treat LDH, as demonstrated in previous studies. The purpose of the present study was to evaluate the outcomes of patients treated using this therapy in a single blind and randomized controlled trial by recording patient report questionnaires and objective test data, and to explore the feasibility and preliminary effects of floating needle therapy for patients with LDH. METHODS: A total of 80 patients who fulfilled the inclusion criteria were randomly divided into a Fu's subcutaneous needling (FSN) group and an acupuncture group then treated in accordance with procedures appropriate for a single blind and randomized controlled trial. The FSN group received 12 FSN therapy sessions over a 3-week period, and the acupuncture group received acupuncture therapy at specified points using acupuncture needles. The principal measurements were scored using the visual analogue scale (VAS), Japanese Orthopedic Association (JOA) Score, and Oswestry disability index (ODI) before and 3 weeks after treatment. Secondary measurements included immune function IgG and IgM measurements performed at the same time and adverse reactions during treatment. RESULTS: The results of this trial will be published on the website of China Clinical Trial Registration Center (http://www.chictr.org.cn/searchprojen.aspx) and in peer-reviewed journals or academic conferences. CONCLUSIONS: This study will explore the feasibility and preliminary effects of floating needle therapy for the treatment of patients with LDH. REGISTRATION: PROSPERO (registration number ChiCTR1900024045).

Influences of circulatory factors on intervertebral disc aging phenotype.

Whether disc aging is influenced by factors beyond its local environment is an important unresolved question. Here we performed heterochronic parabiosis in mice to study the effects of circulating factors in young and old blood on age-associated intervertebral disc degeneration. Compared to young isochronic pairs (Y-Y), young mice paired with old mice (Y-O) showed significant increases in levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic tissue degeneration, but negligible changes in cellular senescence markers (p16INK4a, p21Cip1). Compared to old isochronic pairs (O-O), old mice paired with young mice (O-Y) exhibited a significant decrease in expression of cellular senescence markers (p16, p21, p53), but only marginal decreases in the levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic degeneration. Thus, exposing old mice to young blood circulation greatly suppressed disc cellular senescence, but only slightly decreased disc matrix imbalance and degeneration. Conversely, exposing young mice to old blood accelerated their disc matrix imbalance and tissue degeneration, with little effects on disc cellular senescence. Thus, non-cell autonomous effects of circulating factors on disc cellular senescence and matrix homeostasis are complex and suggest that disc matrix homeostasis is modulated by systemic factors and not solely through local disc cellular senescence.

Inflammatory, Structural, and Pain Biochemical Biomarkers May Reflect Radiographic Disc Space Narrowing: The Johnston County Osteoarthritis Project.

The purpose of this work is to determine the relationship between biomarkers of inflammation, structure, and pain with radiographic disc space narrowing (DSN) in community-based participants. A total of 74 participants (37 cases and 37 controls) enrolled in the Johnston County Osteoarthritis Project during 2006-2010 were selected. The cases had at least mild radiographic DSN and low back pain (LBP). The controls had neither radiographic evidence of DSN nor LBP. The measured analytes from human serum included N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, IL-17, IL-6, BDNF, OPG, and NPY. A standard dolorimeter measured pressure-pain threshold. The coefficients of variation were used to evaluate inter- and intra-assay reliability. Participants with similar biomarker profiles were grouped together using cluster analysis. The binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) in propensity score-matched models. Significant associations were found between radiographic DSN and OPG (RR = 3.90; 95% CI: 1.83, 8.31), IL-6 (RR = 2.54; 95% CI: 1.92, 3.36), and NPY (RR = 2.06 95% CI: 1.62, 2.63). Relative to a cluster with low levels of biomarkers, a cluster representing elevated levels of OPG, RANTES, Lumican, Keratin-19, and NPY (RR = 3.04; 95% CI: 1.22, 7.54) and a cluster representing elevated levels of NPY (RR = 2.91; 95% CI: 1.15, 7.39) were significantly associated with radiographic DSN. Clinical Significance: These findings suggest that individual and combinations of biochemical biomarkers may reflect radiographic DSN. This is just one step toward understanding the relationships between biochemical biomarkers and DSN that may lead to improved intervention delivery. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1027-1037, 2020.