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.

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.

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.

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.

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.

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.