The association between inflammatory biomarkers and low back disorder: a systematic review and meta-analysis.

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.

In subjects with chronic low back pain, does neuropathia exclusively correlated to neuronal compression? A correlation study of PainDETECT questionnaire and corresponding MRI and X-ray findings.

INTRODUCTION: Understanding the complex nature of low back pain (LBP) is crucial for effective management. The PainDETECT questionnaire is a tool that distinguishes between neuropathic (NeP), nociceptive (NoP), and ambiguous pain. This study aimed to investigate the relationship between pain classification and lumbar intervertebral degenerative parameters obtained from imaging. METHODS: A cohort study was conducted involving 279 patients, aged 18 years and above, who completed PainDETECT questionnaires and underwent lumbar MRI and/or X-ray scans. RESULTS: The study included 102 patients with NoP, 78 with ambiguous pain, and 99 with NeP. The NeP group had lower mean age (58.21 vs. 53.63, p < 0.05) and higher mean numerical rating scale score (7.9 vs. 5.9, p < 0.001) compared to the NoP group. A negative correlation was found between PainDETECT scores and pelvic incidence (τ = - 0.177, p = 0.043). The NeP group exhibited significantly higher severity of foraminal stenosis (U = 18.962, p = 0.002), spinal stenosis (U = 14.481, p = 0.005), and Pfirrmann grade (U = 14.221, p = 0.028) compared to the NoP group. A higher proportion of NeP patients had intervertebral disk bulge (96% vs. 78% vs. 78%, p = 0.002) and high-intensity zones (51% vs. 41% vs. 19%, p < 0.001) compared to those with NoP and ambiguous pain. CONCLUSION: NeP, as determined by the PainDETECT questionnaire, is associated with more severe neural compression, increased presence of discogenic disease and inflammatory disk severity, and decreased pelvic incidence. This pioneering study establishes a connection between pathological findings and pain categorization, providing clinicians with valuable guidance for formulating tailored management plans and reducing the need for unnecessary pharmacotherapy, imaging, and non-targeted surgical interventions.

Reconsidering high intensity zones: its role in intervertebral disk degeneration and low back pain.

PURPOSE: High intensity zones (HIZ) in the lumbar intervertebral disk (IVD) can be associated with degenerative changes which may ultimately manifest as low back pain (LBP). However, the relationship between the prevalence of HIZ and lumbar degenerative parameters is still unclear. The purpose of this study was to determine the prevalence of HIZ in the lumbar spine, analyze the independent relationship between HIZ and lumbar degenerative parameters measured on MRI and X-ray and determine the association between HIZ and the presence of LBP. METHODS: A retrospective review of MRI data, X-ray data, and radiology reports for 136 consecutively recruited patients, above 18-years-age and with both lumbar MRI and X-ray scans was conducted. 57 patients with HIZ were identified. Patients without HIZ (n = 79) made up the control group. RESULTS: HIZ was prevalent in 41.9% of patients and in 11.0% of all lumbar IVDs. The odds of developing HIZ were 6.4 (Exp(B) 6.4, 95%CI [3.157-12.988]) and 3.0 (Exp(B) 3.0, 95%CI [1.603, 5.674]) times higher in IVDs with disk bulge/protrusion and nucleus degeneration, respectively. Odds of HIZ was also increased in disks with larger IVD angle (Exp(B) 1.1, 95%CI [1.034, 1.169]). The odds of patients presenting to imaging with LBP was 3.0 (OR 3.0, 95%CI [1.478-6.338]) times higher in the HIZ compared to the control group. CONCLUSIONS: HIZ was prevalent in 41.9% of participants that were recruited in this study. Nucleus degeneration, disk bulge/protrusion and increased IVD angle were found to be independently associated with HIZ and since there is an increased likelihood of LBP, we posit that HIZ is likely a symptomatic and clinically meaningful diagnostic tool in the assessment of LBP.

Is neck pain a marker for something serious? Like myelopathy.

Degenerative Cervical Myelopathy (DCM) is a chronic progressive condition of the cervical spine that leads to compression of the spinal cord. It is the most common cause of spinal cord dysfunction in adults, and it occurs due to age-related changes or genetically associated pathologies. DCM is a clinical and radiological diagnosis and presents with a spectrum of symptoms ranging from neck pain and stiffness to paralysis. While neck pain is prevalent amongst patients attending specialist clinics, its predictive value for DCM is limited. This paper focuses on elucidating the relationship between DCM and chronic neck pain, and we discuss the underlying aetiology and broader neurological implications in the context of the literature. The progression of DCM can be slow and insidious with symptoms worsening gradually over time. Neck pain should not be discounted in the evaluation of DCM.

A confirmatory factor analysis of an electronic format painDETECT questionnaire for patients with low back pain.

BACKGROUND: The substantial burden of low back pain on patients and healthcare systems is exacerbated by unclear pathology and ineffective diagnostic methods, hindering effective management. The painDETECT questionnaire (PD-Q) has been used to facilitate the evaluation and categorization of low back pain. While preliminary validation and translations of the paper-based format of PD-Q into languages such as Spanish and Dutch have been accomplished, the underlying factor model inherent to the electronic format of the PD-Q remains to be established. OBJECTIVE: The objective of this study was to utilise confirmatory factor analysis (CFA) to investigate the factor structure of an electronic format PD-Q among patients with neuropathic low back pain. METHODS: This cross-sectional study was conducted at a Spinal Clinic in Sydney between November 2020 and October 2022. Eligible participants were adults over 18 with low back pain and no history of lumbar surgery or systemic co-morbidities. Participants completed the electronic format of the PD-Q, and CFA was employed to assess the validity of the suggested two-factor, nine-item structure. Recommended cut-offs for goodness-of-fit indices were used to evaluate the model fit. RESULTS: Of the 236 patients that visited the clinic during the data collection period, 142 (71, 50% female, mean age 51.26 ± 15.28 years) participated in the study. Median pain severity was 9/10 over 4 weeks. CFA indicated strong model fit, with goodness-of-fit and comparative fit indices over 0.9, and overall internal consistency was 0.77. Construct validity analysis demonstrated the PD-Q's effectiveness in distinguishing neuropathic, mixed, and nociceptive LBP, aiding neuropathic pain evaluation in low back pain patients. CONCLUSION: This study confirms the reliability and two-factor structure of the electronic PD-Q for neuropathic pain assessment in low back pain patients. To enhance comprehension of the clinical applicability of the electronic format PD-Q, future research should conduct clinimetric evaluations.

Association Between Non-spinal Comorbid Medical Conditions and Neuropathic Low Back Pain. - A Further Unravelling of Pain Complexities in the Context of Back Pain.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Understanding the complex nature of low back pain (LBP) is crucial for effective management. The PainDETECT questionnaire is a tool that distinguishes between neuropathic (NeP) and nociceptive (NoP) low back pain. Traditionally NeP and NoP have been primarily attributed to patho-anatomical abnormalities within the lumbar spine. However, increasing evidence points to multifaceted involvement, encompassing a range of physical, biomechanical, chemical, and psychosocial factors. The study aimed to determine the independent relationship between NeP as assessed by the PainDETECT questionnaire and non-spinal comorbid medical conditions. METHODS: A prospective cohort study was conducted involving 400 patients suffering from chronic LBP (>6months), aged >18 years, who complete the PainDETECT questionnaire and provided responses regarding the presence of any comorbid conditions. A binary logistic regression model was used to analyse the confounding status of comorbid medical conditions and pain severity measured by NRS to determine independent relationships between specific conditions and neuropathic pain. RESULTS: The study included 143 and 257 patients suffering from NeP and NoP, respectively. The NeP group had a 38% higher mean numerical rating scale score compared to the NoP group (8.10 ± 1.55 vs 5.86± 2.26, P < 0.001). The odds of developing NeP were 2.9 Exp(B) = 2.844, 95%C.I. [1.426-5.670], P < 0.01), 2.7 (Exp(B) = 2.726, 95%C.I. [1.183-6.283], P < 0.05) and 2.8 (Exp(B) = 2.847, 95%C.I. [1.473-5.503], P < 0.05) times higher in patients suffering from gastrointestinal conditions, rheumatoid arthritis, and depression, respectively. CONCLUSION: NeP as determined by the PainDETECT questionnaire, is associated with gastrointestinal conditions, rheumatoid arthritis, and depression. This pioneering study has shed light on the potential involvement of the gut microbiome as a common factor connecting non-spinal comorbidities and NeP. These findings underscore the importance of formulating personalized management plans tailored to individual pain and medical profiles, rather than relying on a blanket approach to pain management.

Low back pain classifications and their associations with disability, quality-of-life, and sociodemographic factors: a comprehensive examination using the PainDETECT questionnaire.

BACKGROUND: Low back pain (LBP) is a debilitating phenomenon that significantly impacts quality-of-life (QoL). The PainDETECT questionnaire (PD-Q) is a screening tool aimed at distinguishing nociceptive pain (NoP) and neuropathic pain (NeP) classifications. Associations between these classifications and patient-reported outcome measures (PROMs) and sociodemographic parameters are yet to be established. OBJECTIVE: The study aimed to determine the relationship between NeP as assessed by the PD-Q and pain, disability, QoL, and sociodemographic factors. METHODS: A retrospective analysis of an ongoing prospectively collected database was conducted involving 512 patients aged >18 years who presented to a tertiary spine clinic for LBP having completed the PainDETECT questionnaire, Oswestry Disability Index (ODI), EuroQol Five-Dimensional (EQ-5D) questionnaire, or answered questions regarding sociodemographic status. RESULTS: The NeP group had a higher mean numerical rating scale (NRS) score (7.96±1.54 vs. 5.76±2.27, p <.001) and lower age (55±15.6 vs. 59±17.8, p <.05) compared to the NoP group. When confounded for NRS, analysis of covariance demonstrated an 89.5% higher total ODI score (p <.001) and 50.5% lower EQ-5D utility score (p <.001) in the NeP compared to NoP group. Smokers and individuals with a no partner marital status were 2.373 (OR = 2.373, 95% CI = 1.319-4.266, p <.01) and 2.384 times (OR = 2.384, 95% CI = 1.390-4.092, p <.01) more likely to have NeP compared to NoP, respectively. Patients with NeP were also of lower income class compared to patients with NoP (Z = -2.45, p <.05). CONCLUSION: NeP was associated with higher levels of disability and lower QoL. Smokers, individuals with a no partner marital status, and individuals with a lower income class were more likely to suffer NeP rather than NoP. These findings have illuminated a crucial notion: in patients with elevated NRS, the detrimental impact of NeP on patient wellbeing underscores the fundamental need to represent pain on a nociceptive-neuropathic continuum, permitting more accurate differentiation of pain components.

Nociceptive pain assessed by the PainDETECT questionnaire may predict response to opioid treatment for chronic low back pain.

Introduction: The pharmacological management of chronic low back pain (LBP) is complex. The World Health Organisation recommends a laddered approach to pain medication usage. The PainDETECT questionnaire distinguishes between neuropathic pain (NeP), nociceptive pain (NoP), and ambiguous pain. By elucidating the difference in medication efficacy between these groups, clinicians can provide a tailored treatment plan to manage patient's pain. This study aimed to investigate the relationship between pharmacological treatments, pain categorizations, and medication efficacy as reported by patients. Methods: A secondary retrospective analysis of a prospectively collected database was conducted involving 318 consecutively recruited patients, aged 18 years and above, who completed PainDETECT, medication history and patient reported medication efficacy questionnaires. Medication history was categorized into four lines of treatment: first line (paracetamol ± non-prescribed anti-inflammatories), second line (prescribed anti-inflammatories), third line (anticonvulsants/neuromodulators) and fourth line (opioids). Medication efficacy was measured using a three-point Likert scale: effective (+2), somewhat effective (+1), no effect (0). Findings: The study included 120, 50, 54 and 94 patients on first line, second line, third line and fourth line treatment, respectively. The NeP group had higher mean numerical rating scale (NRS) compared to NoP group in all four lines of treatment (8.10 ± 1.59 vs. 5.47± 2.27, p < 0.001, 8.64± 1.43 vs. 5.52± 1.86, p < 0.001, 8.00± 1.07 vs. 6.37± 2.39, p < 0.01, and 8.05± 1.73 vs. 7.2± 1.29, p < 0.05). When confounding for severity of LBP as measured by NRS, the distribution of medication efficacy significantly differed amongst the NeP, ambiguous and NoP groups in patients undergoing fourth line pharmacological treatment (r2 = 8.623, p < 0.05). The NoP group exhibited significantly higher medication efficacy compared to the NeP group (U = 14.038, p < 0.05). There was no significant difference in medication efficacy across the pain classifications for first, second- and third-line treatment. Interpretation: Opioids was the only line of treatment more effective in targeting NoP, as determined by the PainDETECT questionnaire, compared to NeP. This pioneering study illustrates the complex nature of pharmacological management for chronic LBP. It underscores the importance of tailoring pharmacological treatment plans to fit individual pain profiles and expectations instead of adopting a blanket approach to pain management.

Imaging predictors of progression of lumbar spondylolysis to spondylolisthesis: a systematic review.

BACKGROUND CONTEXT: Isthmic spondylolisthesis (IS) is defined as the anterior translation of one lumbar vertebra relative to the next caudal segment as a result of a unilateral or bilateral fracture of the pars interarticularis. These fractures are interchangeably known as "pars defects" or "spondylolysis." Many risk factors have been proposed to explain the progression of a spondylolytic defect to IS, however, none are validated. PURPOSE: This systematic review provides an overview of various radiological and imaging parameters that can help predict the risk of progression of a spondylolytic defect into IS. STUDY DESIGN: Systematic review. METHODS: Medline, Embase and Cochrane online database were searched. The various correlations between imaging features with observed spondylolisthesis prevalence or severity or spondylolysis rates of spondylolisthesis were evaluated to provide a list of imaging risk factors to predict IS. Significance of the correlations in the original article was recorded to enable comparison of the collected evidence of separate image features. RESULTS: All searches combined generated a total of 431 results of which 26 articles were included into this study. Of the 22 potential risk factors identified, 5 were found to be statistically insignificant, 8 were found to be significant and 9 had mixed results. The following features were found to be significant risk factors in at least on study: disc degeneration, transverse process width, pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, lumbar index, thoracic kyphosis, facet joint angle above the level of defect, facet joint degeneration, facet tropism, multifidus size, lateral erector spinae size, mesenteric fat thickness, subcutaneous fat thickness and soft tissue calcification. CONCLUSION: Our research suggests that only disc degeneration had moderately strong evidence with consistent significant associations with development of IS in patients with spondylolysis. Transverse process width, pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, lumbar index, thoracic kyphosis, facet joint angle above the level of defect, facet joint degeneration, facet tropism, multifidus size, lateral erector spinae size, mesenteric fat thickness, subcutaneous fat thickness and soft tissue calcification had some evidence. All other radiological factors had weak evidence. The results of this study can be used to improve early clinical decision making for patients with spondylolysis.

Spinal column radiological factors associated with increased spinal cord intramedullary signal intensity - A study evaluating aging spinal cord's relation to spinal disc degeneration.

PURPOSE: Increased intramedullary signal intensity (IISI) on T2 weighted MRI scan (T2WI) can be a radiological feature of spinal cord degeneration. However, the association of IISI to degeneration of the spinal column that protects the spinal cord remains unclear. The purpose of this study was to determine the prevalence of IISI and analyze the independent relationship between IISI and cervical degenerative parameters on X-ray and magnetic resonance imaging (MRI). METHODS: A retrospective review of MRI, X-ray, and radiology data (n = 144) adult patients with both cervical MRI and X-ray scans was conducted. A total of 39 (27 %) patients with IISI was identified. The remaining 105 patients without IISI made up the control group. RESULTS: IISI was most frequent in C6-C7 cervical levels. The likelihood of having IISI was 1.947 (Exp(B) 1.947, 95 %CI [1.004-3.776]) times higher in segmental levels with facet joint degeneration. There was an increased likelihood of IISI within the spinal cord with increasing age (Exp(B) 1.034, 95 %CI [1.008-1.060]), maximum spinal cord compression (MSCC) (Exp(B) 1.038, 95 %CI [1.003-1.075]), rotational angle (Exp(B) 1.082, 95 %CI [1.020-1.148]) and posterior disc herniation width (Exp(B) 1.333, 95 %CI [1.017-1.747]) and decreasing Torg-Pavlov ratio (Exp(B) 0.010, 95 %CI [0.001-0.068]). CONCLUSION: IISI was independently associated with increased age, facet joint degeneration, MSCC, rotational angle, posterior herniation width and decreasing Torg-Pavlov angle. Radiologicaldegenerative changesassociated with IISI indicates a potential for identifying predictors of age related spinal cord morphological changes in DCM, which may allow for early intervention strategies in the future.

Establishing a comprehensive care paradigm: Insights from a specialised combined scoliosis clinic in Australia.

Orthopaedic spine surgery, particularly for adult spinal deformity, demands extensive expertise due to its complex pathologies. Surgical success hinges on precise planning, multidisciplinary collaboration, and advanced techniques to correct deformities and restore spinal alignment. This study investigates the efficacy of a Combined Monthly Scoliosis Clinic initiated in April 2022 at Spine Service, St George Private Hospital. The clinic integrates adult and paediatric spine surgeons from Sydney, aiming to provide specialized care and educational opportunities. Patient assessments include physical evaluations and tailored imaging, with treatment strategies discussed collaboratively amongst surgeons, fellows, registrars and students. Over an 18-month period, the clinic assessed 41 patients (average age 50.4 years; 61.0 % female) with diverse spinal conditions. Treatment approaches varied, encompassing spinal fusion, decompression, and conservative management tailored to individual pathologies. The Combined Monthly Scoliosis Clinic exemplifies a comprehensive model for managing complex spinal deformities. It emphasizes collaborative diagnostics, personalized treatment planning, and continuous educational enhancement for trainees and fellows. Patient outcomes underscore the clinic's effectiveness in improving quality of life through tailored interventions. This integrated approach sets a benchmark for global spine care centres, ensuring optimal patient-centric care and advancing clinical standards through ongoing feedback and adaptation.

Radiographic evaluation of lumbar intervertebral disc height index: An intra and inter-rater agreement and reliability study.

PURPOSE: To evaluate intra- and inter-rater agreement and reliability of seven reported disc height index (DHI) measurement methods on standing lateral X-ray of lumbar spine. METHODS: The adult patients who had standing lateral X-ray of lumbar spine were recruited. Seven methods were used to measure DHI of each lumbar intervertebral disc level, including a ratio of sum of anterior and posterior disc height (DH) to disc diameter (Method 1), a ratio of middle DH to mid-vertebral body height (Method 2), a ratio of middle DH to disc diameter (Method 3), a ratio of the mean of anterior, middle, and posterior DH to the sagittal diameter of the proximal vertebral body (Method 4), a ratio of DH to vertebral height which cross the centre of adjacent vertebral bodies (Method 5), a ratio of the mean of anterior, middle, and posterior DH to the mean of proximal and distal vertebral body height (Method 6), and a ratio of the sum of anterior and posterior DH to the sum of superior and inferior disc depth (Method 7). Two raters conducted the measurements (one medical student (SS) and the other an experienced spine surgeon (XC)). Bland and Altmans Limits of Agreement (LOA) with standard difference were calculated to examine intra- and inter-rater agreements between two out of seven methods for DHI. Intra-class correlations (ICC) with 95% confidence intervals were calculated to assess intra- and inter-rater reliability. RESULTS: The intra-rater reliability in DHI measurements for 288 participants were ICCs from 0.807 (0.794, 0.812) to 0.922 (0.913, 0.946) by rater 1 (SS) and from 0.827 (0.802, 0.841) to 0.918 (0.806, 0.823) by rater 2 (XC). Method 2, 3, and 5 on all segmental levels had bias (95 % CI does not include zero) or/and out of the acceptable cut-off proportion (>50 %). A total of 609 outliers in 9174 segmental levels' LOA range. Inter-rater reliability was good-to-excellent in all but method 2 (0.736 (0.712, 0.759)) and method 5 (0.634 (0.598, 0.667)). ICCs of related lines to good-to-excellent reliability methods was excellent in all but only indirect lines in method 1 and 4 (ICCs lie in the range from 0.8 to 0.9). CONCLUSION: Following a structured protocol, intra- and inter-rater reliability was good-to-excellent for most DHI measurement methods on X-ray. However, the complicated methods (more indirect lines) and IVD degeneration (nucleus pulposus degeneration and disc herniation) potentially affected the agreement on inter-rater measurements. Method 7 is the best reproducible method to measure disc height index for all intervertebral disc segmental levels with a good-to-excellent intra- and inter-rater reliability and agreement.