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BACKGROUND: Previous observational studies have shown controversial results about the relationship between lipid levels and low back pain (LBP). Herein, we aimed to explore the potential causal relationship between lipid levels and LBP by using the mendelian randomization (MR) analysis. METHODS: In this two-sample MR study, data were extracted from publicly available MRC Integrative Epidemiology Unit database. Three single-nucleotide polymorphisms (SNPs) of lipid levels [high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TG)] and two SNPs of LBP risk (LBP and back pain) were retrieved and used as genetic instrumental variables. Inverse-variance weighted (IVW), weighted median, MR-Egger, robust adjusted profile score (MR-RAPS), and MR-PRESSO were used to examine the potential causal association between lipid levels and LBP. RESULTS: IVW (fixed effect) estimation indicated that increased HDL-C level was negatively related to the odds of LBP for European populations. [odds ratio (OR) = 0.923, 95% confidence interval (CI): 0.857-0.993, P = 0.0323]. Similar results were also found in IVW (random effect) (OR = 0.923, 95% CI: 0.866-0.983, P = 0.0134), MR-Egger (OR = 0.858, 95%CI: 0.757-0.973, P = 0.0177), MR-RAPS (OR = 0.932, 95%CI: 0.871-0.997, P = 0.0419), and MR-PRESSO (OR = 0.933, 95%CI: 0.880-0.989, P = 0.0198) analyses. Whereas no causal link was observed between LDL-C/TG and LBP risk (P>0.05). CONCLUSION: This two-sample MR study demonstrated a causal relationship between lipid levels and LBP risk. Further investigations are necessary to elucidate the causal association and specific underlying mechanisms by which lipid levels contribute to the development of LBP.
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Dolor de la Región Lumbar , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Triglicéridos , Humanos , Dolor de la Región Lumbar/genética , Dolor de la Región Lumbar/sangre , Dolor de la Región Lumbar/epidemiología , Triglicéridos/sangre , HDL-Colesterol/sangre , Factores de Riesgo , LDL-Colesterol/sangre , Predisposición Genética a la Enfermedad , Lípidos/sangreRESUMEN
OBJECTIVE: Familial Mediterranean fever is the most common monogenic autoinflammatory disease. This study aimed to evaluate the relationship between sacroiliitis observed in familial Mediterranean fever and hematological inflammatory markers. METHODS: In this study, 168 familial Mediterranean fever patients were examined. A total of 61 familial Mediterranean fever patients who had sacroiliac magnetic resonance imaging due to waist and hip pain were included in the study. According to the magnetic resonance imaging findings, patients were divided into two groups: with and without sacroiliitis. The relationship between hematological inflammatory markers and sacroiliitis was investigated. RESULTS: The frequency of sacroiliitis was found to be 13.6% in all familial Mediterranean fever patients and 37.8% in patients with low back pain who underwent sacroiliac magnetic resonance imaging. Neutrophil count, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and systemic immune-inflammatory index were significantly higher in the sacroiliitis group than in the other group, and this difference was found to be statistically significant (p<0.05). As a result of the receiver operating characteristic analysis, it was observed that neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and systemic immune-inflammatory index were very sensitive parameters in determining sacroiliitis in patients with familial Mediterranean fever. CONCLUSION: It was observed that the frequency of sacroiliitis was increased in familial Mediterranean fever patients. It is predicted that hematological inflammatory markers such as neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and systemic immune-inflammatory index can be used in the diagnosis of sacroiliitis.
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Biomarcadores , Fiebre Mediterránea Familiar , Imagen por Resonancia Magnética , Neutrófilos , Sacroileítis , Humanos , Fiebre Mediterránea Familiar/sangre , Fiebre Mediterránea Familiar/complicaciones , Sacroileítis/sangre , Sacroileítis/diagnóstico por imagen , Femenino , Masculino , Adulto , Biomarcadores/sangre , Adulto Joven , Adolescente , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/sangre , Curva ROC , Recuento de Leucocitos , Monocitos , Linfocitos , Persona de Mediana EdadRESUMEN
INTRODUCTION: Low back disorder (LBD) is a major cause of disability worldwide. Inflammation results in proliferation of cytokines or consequent degradation products (collectively known as inflammatory biomarkers) that activate pain pathways which can result in non-specific LBD. This systematic review and meta-analysis aim to evaluate the relationship between inflammatory biomarkers and clinical outcomes in patients with LBD. METHODS: The PRISMA guideline was followed for the systematic reivew. Three online databases were searched. Four RCTs and sixteen observational studies with 1142 LBD patients were analysed. The primary outcomes were back and leg pain scores, back-specific disability scores and expression of inflammatory biomarkers. Standardized mean difference (SMD) and their 95% confidence intervals (CI) were evaluated. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to summarize the strength of evidence. RESULTS: Four RCTs and sixteen observational studies were included in the analysis of 1142 patients with LBD. There was a statistically significant reduction in back pain score and IL-1 beta and increase in the expression of CTX-1 and IL-10 levels post treatment. There was a significant relationship between increase in the expression of MCP- and reduction in the expression of hsCRP with increase in back pain. Significant relationship was also observed between increase in the expression of MCP-1 and reduction in the expression of IL-6 with increase in leg pain. Increase in the expression of IL-8 and reduction in the expression of hsCRP was also associated with increased disability score. CONCLUSION: Inflammatory biomarkers play a significant role in the pathogenesis of LBD. CTX-1, IL-10 and IL-1 beta may be responsible for the decrease in back pain scores post treatment. There is a relationship between MCP-1, IL-6, IL-8 and hsCRP with clinical and functional assessments for LBD. Further studies will improve understanding of the pathogenesis of LBD and aid in targeted management strategies.
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Biomarcadores , Inflamación , Dolor de la Región Lumbar , Humanos , Biomarcadores/sangre , Dolor de la Región Lumbar/sangre , Inflamación/sangre , Interleucina-10/sangre , Interleucina-1beta/sangre , Quimiocina CCL2/sangre , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Interleucina-6/sangre , Citocinas/sangre , Interleucina-8/sangre , Estudios Observacionales como AsuntoRESUMEN
BACKGROUND: Patients with acute vertebral compression fractures (aVCFs) are frequently transferred to an emergency department by ambulance. The most useful imaging modality is magnetic resonance imaging (MRI); however, which patients should be prioritized for MRI evaluation may be unclear. The aim of this study was to evaluate plasma D-dimer levels as a biomarker for aVCFs. METHODS: This retrospective cohort study included patients with low back pain in the emergency department between November 2017 and October 2020. Patients with infections, patients with coagulation disorders, and patients without D-dimer level measurements were excluded. The presence of an aVCF was detected with MRI. Blood samples were collected for routine blood tests. The predictive factors for aVCFs were evaluated with univariate and multivariable logistic regression analyses. RESULTS: Overall, 191 consecutive MRI evaluations were ordered. After exclusions, 101 patients were reviewed. Based on MRI, 65 (64.4%) patients were diagnosed with aVCF. The presence of aVCF was significantly correlated with age (odds ratio [OR] = 1.052, 95% confidence interval [CI] 1.018-1.191), an old vertebral compression fracture (OR = 3.290, 95% CI 1.342-8.075), hemoglobin (OR = 0.699, 95% CI 0.535-0.912), and D-dimer levels (OR = 1.829, 95% CI 1.260-2.656). Results from a multivariable logistic regression analysis showed that D-dimer levels (OR = 1.642, 95% CI 1.188-2.228) remained a significant risk factor for the presence of aVCFs after adjustment for potential confounders. CONCLUSIONS: Plasma D-dimer levels can provide useful diagnostic information about whether an aVCF is present.
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Biomarcadores , Servicio de Urgencia en Hospital , Productos de Degradación de Fibrina-Fibrinógeno , Fracturas por Compresión , Dolor de la Región Lumbar , Imagen por Resonancia Magnética , Fracturas de la Columna Vertebral , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Femenino , Masculino , Fracturas por Compresión/sangre , Fracturas por Compresión/diagnóstico por imagen , Fracturas por Compresión/complicaciones , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Fracturas de la Columna Vertebral/sangre , Fracturas de la Columna Vertebral/diagnóstico por imagen , Dolor de la Región Lumbar/sangre , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/diagnóstico , Biomarcadores/sangre , Anciano de 80 o más Años , Estudios de Cohortes , AdultoRESUMEN
ABSTRACT: Chronic low back pain (cLBP) is a global health crisis that disproportionately burdens non-Hispanic Black (NHB) individuals, compared with those who identify as non-Hispanic White (NHW). Despite the growing personal and societal impact of cLBP, its biological underpinnings remain poorly understood. To elucidate the biological factors that underlie the racial disparities in cLBP, this study sought to determine whether inflammatory mediators associated with pain interference (PI), pain at rest (PAR), and movement-evoked pain (MEP) differ as a function of racial identity. Blood samples were collected from 156 individuals with cLBP (n = 98 NHB participants, n = 58 NHW participants). Enzyme-linked immunosorbent assay and multiplex assays were used to quantify concentrations of proinflammatory (fibrinogen, C-reactive protein [CRP], serum amyloid A, tumor necrosis factor α [TNF-α], and interleukin [IL]-1α, IL-1ß, and IL-6) and anti-inflammatory markers (IL-4 and IL-13). Spearman rho correlations were used to assess associations among markers of inflammation and PI, PAR, and MEP using the Brief Pain Inventory-Short Form. Analyses revealed that for NHW patients, CRP, serum amyloid A, and IL-6 were positively associated with cLBP outcomes and IL-4 was inversely associated with PAR and MEP. However, for NHB patients, only IL-1α was positively associated with PAR. Our findings suggest that, while there are associations between inflammation and cLBP outcomes, the biomarkers that underlie the inflammation could very well differ as a function of racialized minority group. However, more research with racially inclusive samples is needed to elucidate the mechanisms that may contribute to racial disparities in cLBP.
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Dolor Crónico , Dolor de la Región Lumbar , Población Blanca , Humanos , Masculino , Dolor de la Región Lumbar/sangre , Dolor de la Región Lumbar/etnología , Femenino , Persona de Mediana Edad , Adulto , Dolor Crónico/sangre , Dolor Crónico/etnología , Mediadores de Inflamación/sangre , Negro o Afroamericano , Biomarcadores/sangre , Dimensión del Dolor/métodos , Anciano , Inflamación/sangreRESUMEN
BACKGROUND: Low back pain (LBP) is a common musculoskeletal condition and a major cause of disability worldwide. Previous studies have found associations of biomarkers with pain and pain-related disability in LBP patients. This study aimed to explore the association between serum biomarkers and pain and disability in patients with acute or subacute axial LBP. METHODS: This study was ancillary to a parent randomized controlled trial. Enrolled participants were randomized into three intervention groups: one of two types of spinal manipulation or medical care. In the parent study, 107 adults who experienced a new episode of LBP within 3 months prior to enrollment were recruited. For this study, 90 of these 107 participants consented to have blood samples obtained, which were drawn immediately before the beginning of treatment. Seven biomarkers were chosen based on previous literature and analyzed. Clinical outcomes were pain and Oswestry Disability Index (ODI) evaluated at baseline and 4 weeks. Spearman's |r| was used to study the association of initial levels of each biomarker with pain and ODI scores at baseline and with changes in outcome scores from baseline to 4 weeks (end of treatment) within each intervention group. RESULTS: At baseline, 4 of 7 biomarkers had an association with pain that was |r| ≥ .20: neuropeptide Y (NPY) (r = 0.23, p = .028), E-Selectin (r = 0.22, p = .043), vitamin D ((r = - 0.32, p = .002), and c-reactive protein (CRP) (r = 0.37, p = .001). No baseline biomarker had an association with disability that was |r| ≥ 0.20. For the correlations of baseline biomarkers with 4-week change in outcomes, vitamin D showed a correlation with change in disability and/or pain (|r| ≥ 0.20, p > .05) in manipulation-related groups, while CRP, NPY, and E-selectin along with TNFα, Substance P and RANTES showed at least one correlation with change in pain or disability (|r| ≥ 0.20, p > .05) in at least one of the treatment groups. CONCLUSIONS: In 90 LBP patients, the analyzed biomarkers, especially vitamin D, represent a small set of potential candidates for further research aimed at individualizing patient care. Overall, the associations investigated in the current study are an initial step in identifying the direct mechanisms of LBP and predicting outcomes of manipulation-related treatments or medical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01211613, Date of Registration: September 29, 2010, https://clinicaltrials.gov/ct2/show/NCT01211613?term=schneider&cond=Low+Back+Pain&cntry=US&state=US%3APA&draw=2&rank=1.
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Dolor de la Región Lumbar , Vitamina D , Adulto , Humanos , Biomarcadores/sangre , Selectina E/sangre , Dolor de la Región Lumbar/sangre , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/terapia , Dimensión del Dolor , Resultado del Tratamiento , Vitamina D/sangreRESUMEN
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.
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Degeneración del Disco Intervertebral , Dolor de la Región Lumbar , Factores de Crecimiento Nervioso , Vibración , Animales , Masculino , Ratas , Degeneración del Disco Intervertebral/sangre , Degeneración del Disco Intervertebral/complicaciones , Degeneración del Disco Intervertebral/diagnóstico , Dolor de la Región Lumbar/sangre , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/etiología , Factores de Crecimiento Nervioso/sangre , Ratas Sprague-Dawley , Vibración/efectos adversosRESUMEN
CONTEXT: Over 9 million epidural steroid injections (ESIs) are performed annually in the United States. Although these injections effectively treat lumbar radicular pain, they may have adverse consequences, including bone loss. OBJECTIVE: To investigate acute changes in bone turnover following ESI. We focused on postmenopausal women, who may be at greatest risk for adverse skeletal consequences due to the combined effects of ESIs with aging and estrogen deficiency. METHODS: Single-center prospective observational study. Postmenopausal women undergoing lumbar ESIs and controls with no steroid exposure were included. Outcomes were serum cortisol, markers of bone formation, osteocalcin, and procollagen type-1 N-terminal propeptide (P1NP), and bone resorption by C-telopeptide (CTX) measured at baseline, 1, 4, 12, 26, and 52 weeks after ESIs. RESULTS: Among ESI-treated women, serum cortisol declined by ~50% 1 week after injection. Bone formation markers significantly decreased 1 week following ESIs: osteocalcin by 21% and P1NP by 22%. Both markers remained suppressed at 4 and 12 weeks, but returned to baseline levels by 26 weeks. There was no significant change in bone resorption measured by CTX. Among controls, there were no significant changes in cortisol or bone turnover markers. CONCLUSION: These results provide evidence of an early and substantial reduction in bone formation markers following ESIs. This effect persisted for over 12 weeks, suggesting that ESIs may have lasting skeletal consequences. Given the large population of older adults who receive ESIs, further investigation into the long-term skeletal sequelae of these injections is warranted.
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Remodelación Ósea , Resorción Ósea , Glucocorticoides , Dolor de la Región Lumbar , Osteogénesis , Posmenopausia , Anciano , Biomarcadores/sangre , Densidad Ósea , Remodelación Ósea/efectos de los fármacos , Resorción Ósea/inducido químicamente , Femenino , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Humanos , Hidrocortisona/sangre , Inyecciones Epidurales , Dolor de la Región Lumbar/sangre , Dolor de la Región Lumbar/tratamiento farmacológico , Osteocalcina/sangre , Osteogénesis/efectos de los fármacosRESUMEN
A comprehensive analysis of clinical information in patients with chronic low back pain (CLBP) was performed to clarify the clinical characteristics of geriatric LBP from the perspective of body composition, spinal alignment, and blood findings related to senescence. We enrolled 203 patients with an average age of 79.0 years (77 men and 126 women), with non-specific CLBP as a single-center prospective cohort study, the patients were compared with age- and sex-matched controls without CLBP using a propensity score-matching. We performed laboratory analysis, radiographic evaluations for global spinal parameter and lumbar degeneration, and body composition analysis using whole-body dual-energy X-ray absorptiometry. We observed a higher red blood cell distribution width (RDW) (p < 0.001), which is an index of aging, as well as a lower vitamin D level (p = 0.002), skeletal muscle mass index (p = 0.045) and a higher fat mass (p = 0.007) in patients with CLBP. Moreover, patients with geriatric CLBP had significantly lower lumbar lordosis (p = 0.024), and higher sagittal vertical axis (p = 0.006) was correlated with lower extremity and trunk muscle mass (p < 0.001), independent of lumbar degeneration. Geriatric patients with CLBP have sarcopenic fat accumulation and spinal sagittal malalignment with senescent status, such as elevated RDW and hypovitaminosis D.
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Dolor de la Región Lumbar/sangre , Dolor de la Región Lumbar/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Composición Corporal , Enfermedad Crónica , Estudios de Cohortes , Femenino , Humanos , Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Lordosis , Dolor de la Región Lumbar/etiología , Vértebras Lumbares/diagnóstico por imagen , Masculino , Músculo Esquelético , Estudios Prospectivos , RadiografíaRESUMEN
Aim: To compare the hematological parameters associated with systemic inflammation between acute and subacute/chronic nonspecific low back pain and to evaluate their diagnostic roles in relation to chronicity in low back pain. Materials & methods: This retrospective case-control study included 150 participants aged 18-65 years with acute nonspecific low back pain, 150 with subacute/chronic nonspecific low back pain, 150 as the control group. Results: Red cell distribution width was significantly higher in the subacute/chronic pain group compared with the acute pain group (p = 0.003), and had a poor diagnostic value for chronicity (cutoff: 11.95, p = 0.003). There were no significant differences in terms of other parameters (p > 0.05). Conclusion: Red cell distribution width has a poor diagnostic value for chronicity in nonspecific low back pain.
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Inflamación/sangre , Dolor de la Región Lumbar/sangre , Adolescente , Adulto , Anciano , Animales , Dolor Crónico , Femenino , Pruebas Hematológicas , Humanos , Dolor de la Región Lumbar/complicaciones , Ratones , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Evidence on the latest technologies in rehabilitation for reducing pain and altering serum stress hormones in low back pain (LBP) was lacking. OBJECTIVE: To find the clinical and hormonal effects of virtual reality training (VRT) and isokinetic training (IKT) in chronic LBP patients. METHODS: Through the simple random sampling method, 60 university football players with chronic LBP were allocated into three groups: NVRT= 20, NIKT= 20 and NCONTROL= 20. The three groups underwent different exercises for 4 weeks. Clinical (pain intensity and kinesiophobia) and hormonal (glucose, insulin, HOMA-IR, growth hormone, prolactin, ACTH and cortisol) values were measured at baseline, after 4 weeks and 6 months. RESULTS: Four weeks following training, the VRT and IKT groups showed significant changes in pain intensity and kinesiophobia in comparison to the control group (p< 0.05). Hormonal measures also showed significant improvement in the VRT group in comparison to the other two groups (p< 0.05). CONCLUSION: Training through virtual reality and isokinetic exercise is an effective approach in terms of pain and kinesiophobia. In terms of hormonal analysis, virtual reality shows slightly more improvements than isokinetic training in subjects with chronic LBP.
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Dolor Crónico , Dolor de la Región Lumbar , Realidad Virtual , Dolor Crónico/sangre , Dolor Crónico/terapia , Terapia por Ejercicio , Hormonas , Humanos , Dolor de la Región Lumbar/sangre , Dolor de la Región Lumbar/terapia , Masculino , Dimensión del DolorRESUMEN
OBJECTIVE: The contributions of intervertebral disc disease and subject-specific covariates to systemic inflammation in low back pain are unknown. We examined the effects of symptomatic disc herniation (DH) and MRI herniation severity on serum cytokine levels in clinical subjects. DESIGN: Cytokine levels from lumbar DH subjects (N = 78) were compared to control subjects (N = 57) accounting for effects of DH, age, body mass index (BMI) and gender. Effect of DH severity on cytokine levels was analyzed on subsets of subjects with acute or chronic pain. Serum cytokines were also analyzed in a subset of patients between pre- and 3 months post-surgery. RESULTS: Cytokine levels were elevated in the serum of patients with symptomatic DH, and the covariates age, BMI and gender significantly contributed to levels of some cytokines. Severity of herniation was a significant contributor to pain intensity (VAS), serum levels of HMGB1, PDGFbb, and IL-9. The relationship between DH severity and cytokine levels was confirmed in subjects with chronic, but not acute symptoms. Serum levels of macrophage migration inhibitory factor (MIF) decreased, whereas levels of CCL3, CCL11, CXCL1, and CXCL10 were significantly elevated post surgery. CONCLUSIONS: This study is the first to show that DH severity is coordinately associated with changes in serum levels of inflammatory cytokines in chronic pain subjects. HMGB1, PDGFbb and IL-9 are novel mediators of increasing DH severity, indicative of cellular damage, neuro-inflammation and angiogenesis. Resolution of inflammation was observed with decrease in MIF post surgery. However, elevated chemokine levels indicate ongoing remodeling and wound healing at 3-month time point.
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Citocinas/sangre , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Dolor de la Región Lumbar/sangre , Dolor Agudo/sangre , Dolor Agudo/fisiopatología , Adulto , Factores de Edad , Becaplermina/sangre , Índice de Masa Corporal , Quimiocina CCL11/sangre , Quimiocina CCL3/sangre , Quimiocina CXCL1/sangre , Quimiocina CXCL10/sangre , Quimiocinas/sangre , Dolor Crónico/sangre , Dolor Crónico/fisiopatología , Femenino , Proteína HMGB1/sangre , Humanos , Interleucina-9/sangre , Desplazamiento del Disco Intervertebral/sangre , Desplazamiento del Disco Intervertebral/fisiopatología , Dolor de la Región Lumbar/fisiopatología , Vértebras Lumbares , Factores Inhibidores de la Migración de Macrófagos/sangre , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Radiculopatía/sangre , Radiculopatía/fisiopatología , Índice de Severidad de la Enfermedad , Factores SexualesRESUMEN
OBJECTIVE: This study was undertaken to identify novel autoantibodies in axial spondyloarthritis (SpA) and determine their diagnostic potential in patients with early axial SpA and controls from 2 independent cohorts. METHODS: An axial SpA complementary DNA phage display library was used to screen for novel IgG antibodies in plasma from patients with early axial SpA. The presence of these antibodies against novel peptides (i.e., peptides identified in an early axial SpA cohort from Hasselt University, designated UH-axSpA) was determined by enzyme-linked immunosorbent assay in 76 patients with early axial SpA, 75 controls with nonspecific chronic low back pain, 60 patients with rheumatoid arthritis, and 94 healthy controls from the UH cohort. Antibody reactivity to these novel peptides was further validated in 174 patients with axial SpA (of whom 79 had early axial SpA) from the University Hospitals Leuven (Bio)SPAR (Spondyloarthritis [Biologics]) cohort. RESULTS: We identified antibodies to 9 novel UH-axSpA peptides, corresponding to randomly formed peptides and to a novel axial SpA autoantigen, double homeobox protein 4. Antibodies to 3 UH-axSpA peptides with the highest positive likelihood ratio (LR) for a diagnosis of axial SpA were present in significantly more patients with early axial SpA from the UH and (Bio)SPAR cohorts (14.2% [22/155]) compared to controls with chronic low back pain (5% [4/75]), resulting in 95% specificity. The positive LR for confirming axial SpA using antibodies to these 3 UH-axSpA peptides was 2.7, which is higher than the LR obtained with the currently used laboratory marker C-reactive protein. Testing for antibodies to these 3 UH-axSpA peptides in patients with chronic low back pain increased the posttest probability of a diagnosis of axial SpA from 79% to 91%. CONCLUSION: Antibodies to 3 UH-axSpA peptides could provide a novel tool in the diagnosis of a subset of axial SpA patients.
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Autoanticuerpos/sangre , Dolor de la Región Lumbar/inmunología , Espondiloartritis/inmunología , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Femenino , Humanos , Dolor de la Región Lumbar/sangre , Masculino , Persona de Mediana Edad , Espondiloartritis/sangreRESUMEN
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.
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Citocinas/sangre , Desplazamiento del Disco Intervertebral/sangre , Dolor de la Región Lumbar/sangre , Ciática/sangre , Biomarcadores/sangre , Humanos , Degeneración del Disco Intervertebral/sangre , Desplazamiento del Disco Intervertebral/inmunología , Dolor de la Región Lumbar/etiología , Ciática/inmunologíaRESUMEN
BACKGROUND: Low back pain (LBP) is one of the greatest contributors to disability in the world and there is growing interest on the role of biomarkers in LBP. To purpose of this review was to analyze available evidence on the relationship between inflammatory biomarkers, clinical presentation, and outcomes in patients with acute, subacute and chronic non-specific low back pain (NSLBP). METHODS: A search was performed in Medline, Embase, Cinahl and Amed databases. Studies which measured levels of inflammatory biomarkers in participants with NSLBP were included. Two reviewers independently screened titles and abstracts, full-texts, and extracted data from included studies. Methodological quality was assessed using the Newcastle Ottawa Quality Assessment Scale. Level of evidence was assessed using the modified GRADE approach for prognostic studies. RESULTS: Seven primary studies were included in this review. All results assessed using the modified GRADE demonstrated low to very low quality evidence given the small number of studies and small sample. Three studies examined C-reactive protein (CRP), one of which found significantly higher CRP levels in an acute NSLBP group than in controls and an association between high pain intensity and elevated CRP. Three studies examined tumor necrosis factor alpha (TNF-α), two of which found elevated TNF-α in chronic NSLBP participants compared to controls. Two studies examined interleukin 6 (IL-6), none of which found a significant difference in IL-6 levels between NSLBP groups and controls. Two studies examined interleukin 1 beta (IL-ß), none of which found a significant difference in IL-ß levels between NSLBP groups and controls. CONCLUSIONS: This review found evidence of elevated CRP in individuals with acute NSLBP and elevated TNF-Α in individuals with chronic NSLBP. There are a limited number of high-quality studies evaluating similar patient groups and similar biomarkers, which limits the conclusion of this review.
Asunto(s)
Dolor Agudo/sangre , Dolor Crónico/sangre , Mediadores de Inflamación/sangre , Dolor de la Región Lumbar/sangre , Dolor Agudo/diagnóstico , Biomarcadores/sangre , Dolor Crónico/diagnóstico , Humanos , Dolor de la Región Lumbar/diagnósticoRESUMEN
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.
Asunto(s)
Biomarcadores/sangre , Degeneración del Disco Intervertebral/complicaciones , Dolor de la Región Lumbar/etiología , Osteoartritis de la Columna Vertebral/complicaciones , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Degeneración del Disco Intervertebral/sangre , Dolor de la Región Lumbar/sangre , Masculino , Persona de Mediana Edad , Osteoartritis de la Columna Vertebral/sangreRESUMEN
OBJECTIVES: Low back pain (LBP) is a common medical problem worldwide. The aim of this study is to evaluate the association between serum concentration of 25-hydroxivitamin D3 and functional disability in patients suffering from LBP in a sample of Azeri middle-aged subjects, North West of Iran. RESULTS: In this case-control study, 63 eligible patients with LBP and 55 healthy subjects enrolled in the study. Peripheral venous blood was taken for evaluating the serum concentration of 25-hydroxivitamin D3. We recognized factors related with LBP by multiple regression analyses. The average serum 25-hydroxivitamin D3 concentration in case group was significantly lower than that of the matched controlled group (26.25 ± 15.95 vs. 34.20 ± 14.92, p-value < 0.01 respectively). Subjects with vitamin D deficiency or insufficiency were more likely to exhibit LBP than subjects with normal serum 25-hydroxivitamin D3 concentration [(OR = 2.388, 95% CI (1.114 to 5.119)]. According to the partial correlation analysis, there was a reverse correlation between serum 25-hydroxivitamin D3 concentration with functional disability measured by Modified Oswestry Questionnaire (r = - 0.307, p = 0.017) and also with pain intensity according to Visual Analogue Scale (VAS) score (r = - 0.268, p = 0.040) whilst adjusting for age, sex and body mass index (BMI).
Asunto(s)
Calcifediol/sangre , Evaluación de la Discapacidad , Dolor de la Región Lumbar/sangre , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana EdadRESUMEN
We aimed to compare serum biomarkers of inflammation, redox status and cartilage degradation between chronic low back pain (cLBP) patients with and without Modic 1 changes. We used a convenience sample of patients recruited from a single center, case-control study, conducted in a tertiary care center. From December, 2014 to May, 2016, 2,292 patients were consecutively screened, 34 met inclusion criteria and were prospectively enrolled in the present study. Cases (n = 13) were defined as patients with Modic 1 changes detected on MRI and controls (n = 21) as cLBP patients without (Modic 0). To assess serum biomarkers of inflammation, redox status and cartilage degradation, fasting serum samples were collected in a standardized manner and analyzed by immunoassays and spectrophotometry. Mean (95% CI) age was 44.1 (40.0-48.1) years and mean LBP duration was 72.5 (53.0-91.9) months. Serum biomarkers of inflammation (IL-1ß, IL-6, IL-8 and TNF-α), redox status (total thiols, advanced oxidation protein products and carbonyl groups) and cartilage degradation (Coll2-1 and Coll2-1NO2) did not differ between cLBP patients with and without Modic 1 changes. In summary, we did not find any differences in serum biomarkers between cLBP patients with and without Modic 1 changes. Interpretation is limited by convenience sampling and small sample size.
Asunto(s)
Biomarcadores/sangre , Dolor Crónico/sangre , Citocinas/sangre , Dolor de la Región Lumbar/sangre , Adulto , Estudios de Casos y Controles , Dolor Crónico/diagnóstico por imagen , Femenino , Humanos , Dolor de la Región Lumbar/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Estudios Prospectivos , Tamaño de la Muestra , Centros de Atención TerciariaRESUMEN
BACKGROUND: The pathogenesis of low back pain (LBP) remains unclear. However, recent studies suggest that the inflammatory response may be inherent in spinal pain. The purpose of this study was to discern inflammatory profiles in patients with nonspecific acute and chronic LBP in relation to those in asymptomatic individuals. MATERIALS AND METHODS: Peripheral blood samples were obtained from asymptomatic controls and patients with nonspecific acute and chronic LBP reporting a minimum pain score of 3 on a 10-point Visual Analogue Scale (VAS). The levels of in vitro production of proinflammatory (tumor necrosis factor α [TNFα], interleukin [IL] 1ß, IL-6, IL-2, interferon γ) and anti-inflammatory (IL-1 receptor antagonist, soluble receptors of TNF2, and IL-10) mediators were determined by specific immunoassays. RESULTS: The mean VAS scores were comparable between the acute and chronic LBP patient groups. Compared with asymptomatic group, the production of TNFα, IL-1ß, IL-6 and their ratios to IL-10 levels were significantly elevated in both patient groups (P=0.0001 to 0.003). In acute LBP group, the ratio of IL-2:IL-10 was also significantly increased (P=0.02). In contrast, the production of interferon γ was significantly reduced compared with the other study groups (P=0.005 to 0.01), nevertheless, it was positively correlated (P=0.006) with pain scores. In chronic LBP patients, the production of TNFα, IL-1 receptor antagonist, and soluble receptors of TNF2 was significantly increased (P=0.001 to 0.03) in comparison with the control and acute LBP groups, and TNFα and IL-1ß levels were positively correlated (P<0.001) with VAS scores. CONCLUSIONS: The inflammatory profiles of patients with acute and chronic LBP are distinct. Nonetheless, in both patient groups, an imbalance between proinflammatory and anti-inflammatory mediator levels favors the production of proinflammatory components.
Asunto(s)
Dolor Agudo/sangre , Dolor Crónico/sangre , Mediadores de Inflamación/sangre , Inflamación/sangre , Dolor de la Región Lumbar/sangre , Adulto , Femenino , Humanos , Interleucina-1beta/sangre , Interleucina-2/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
Variation of natural antibody (nAb) levels to the pain bioregulators (ß-endorphin, orphanin, serotonin, dopamine, histamine, and angiotensin) in blood serum at chronic low back pain (LBP) was studied for 21 days. We revealed gender features of immuno-profiles: more elevated nAb levels in women at 1st day and equal levels in gender groups at 21st day. In addition, nAb levels remained above normal up to day 21 in most of patients despite a threefold decrease in pain intensity, measured using a differential visual analogue scale. A significant decrease in nAb levels was found in 4-20% of patients depending on the bioregulator. These observations support the hypothesis that antibodies can be a factor in the prolongation of pain. Therefore, the analysis of the dynamics of nAbs can be recommended for patients with LBP, from which it is possible to predict the further course of the disease.