Key role of CCR2-expressing macrophages in a mouse model of low back pain and radiculopathy.
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ABSTRACT:
SUBMITTER: Zhang L
PROVIDER: S-EPMC7758110 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In a recently published genome-wide association study (GWAS) chronic back pain was associated with three loci; SOX5, CCDC26/GSDMC and DCC. This GWAS was based on a heterogeneous sample of back pain disorders, and it is unknown whether these loci are of clinical relevance for low back pain (LBP) with persistent radiculopathy. Thus, we examine if LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy is associated with the selected single nucleotide polymorphisms (SNPs); SOX5 rs34616559, CCDC26/GSDMC rs7833174 and DCC rs4384683. In this prospective cohort study, subjects admitted to a secondary health care institution due to an acute episode of LBP with radiculopathy, reported back pain, leg pain, and Oswestry Disability Index (ODI), were genotyped and followed up at 12 months (n = 338). Kruskal-Wallis H test showed no association between the SNPs and back pain, leg pain or ODI. In conclusion, LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy, is not associated with the selected SNPs; SOX5 rs34616559, CCDC26/GSDMC rs7833174 and DCC rs4384683. This absent or weak association suggests that the SNPs previously associated with chronic back pain are not useful as prognostic biomarkers for LBP with persistent radiculopathy.
| S-EPMC8819060 | biostudies-literature
Project description:BACKGROUND:For many years, low back pain has been both the leading cause of days lost from work and the leading indication for medical rehabilitation. The goal of the German Disease Management Guideline (NDMG) on nonspecific low back pain is to improve the treatment of patients with this condition. METHODS:The current update of the NDMG on non-specific low back pain is based on articles retrieved by a systematic search of the literature for systematic reviews. Its recommendations for diagnosis and treatment were developed by a collaborative effort of 29 scientific medical societies and organizations and approved in a formal consensus process. RESULTS:If the history and physical examination do not arouse any suspicion of a dangerous underlying cause, no further diagnostic evaluation is indicated for the time being. Passive, reactive measures should be taken only in combination with activating measures, or not at all. When drugs are used for symptomatic treatment, patients should be treated with the most suitable drug in the lowest possible dose and for as short a time as possible. CONCLUSION:A physician should be in charge of the overall care process. The patient should be kept well informed over the entire course of his or her illness and should be encouraged to adopt a healthful lifestyle, including regular physical exercise.
| S-EPMC5769319 | biostudies-other
Project description:End plates serve as the interface between rigid vertebral bodies and pliant intervertebral disks. Because the lumbar spine carries significant forces and disks don't have a dedicated blood supply, end plates must balance conflicting requirements of being strong to prevent vertebral fracture and porous to facilitate transport between disk cells and vertebral capillaries. Consequently, end plates are particularly susceptible to damage, which can increase communication between proinflammatory disk constituents and vascularized vertebral bone marrow. Damaged end plate regions can be sites of reactive bone marrow lesions that include proliferating nerves, which are susceptible to chemical sensitization and mechanical stimulation. Although several lines of evidence indicate that innervated end plate damage can be a source of chronic low back pain, its role in patients is likely underappreciated because innervated damage is poorly visualized with diagnostic imaging. This literature review summarizes end plate biophysical function and aspects of pathologic degeneration that can lead to vertebrogenic pain. Areas of future research are identified in the context of unmet clinical needs for patients with chronic low back pain.
| S-EPMC3854605 | biostudies-other
Project description:PURPOSE:Low back pain (LBP) is a common ailment in most developed countries. Because most cases of LBP are known as 'non-specific', it has been challenging to develop experimental pain models of LBP which reproduce patients' clinical pain. In addition, previous models have limited applicability in a steady-pain-state neuroimaging environment. Thus, this study aims to devise a low back pain model with a simple methodology to induce experimental LBP, which has similar pain properties to patients' clinical pain, and to apply the model in a steady-pain-state neuroimaging study. METHODS:Our low back extension (LBE) pain model was tested on 217 LBP patients outside the magnetic resonance imaging (MRI) scanner to determine the reproducibility of endogenous pain and the similarity to their own clinical pain (STUDY1), and applied in a steady-pain-state functional MRI study (47 LBP patients and 23 healthy controls) to determine its applicability (induced head motions and brain functional connectivity changes; STUDY2). RESULTS:By the LBE pain model, 68.2% of the LBP patients reported increased LBP with high similarity of sensations to their own clinical pain (STUDY1), and the head motions were statistically similar to and correlated with those in resting state (STUDY2). Furthermore, the LBE model altered brain functional connectivity by decreasing the default-mode and the sensorimotor networks, and increasing the salience network, which was significantly associated with the intensity of the induced pain. Conversely, the healthy controls showed increased somatosensory network (but not of the cognitive pain processing). CONCLUSION:Our investigations suggest that our LBE pain model, which increased LBP with high similarity to the LBP patients' own pain sensation and induced patient-specific brain responses with acceptable head motion, could be applied to neuroimaging studies investigating brain responses to different levels of endogenous LBP.
| S-EPMC7263586 | biostudies-literature
Project description: Not available
| S-EPMC8078578 | biostudies-literature
Project description:BackgroundFor decades, dementia has been characterized by accumulation of waste in the brain and low-grade inflammation. Over the years, emerging studies highlighted the involvement of the immune system in neurodegenerative disease emergence and severity. Numerous studies in animal models of amyloidosis demonstrated the beneficial role of monocyte-derived macrophages in mitigating the disease, though less is known regarding tauopathy. Boosting the immune system in animal models of both amyloidosis and tauopathy, resulted in improved cognitive performance and in a reduction of pathological manifestations. However, a full understanding of the chain of events that is involved, starting from the activation of the immune system, and leading to disease mitigation, remained elusive. Here, we hypothesized that the brain-immune communication pathway that is needed to be activated to combat tauopathy involves monocyte mobilization via the C-C chemokine receptor 2 (CCR2)/CCL2 axis, and additional immune cells, such as CD4+ T cells, including FOXP3+ regulatory CD4+ T cells.MethodsWe used DM-hTAU transgenic mice, a mouse model of tauopathy, and applied an approach that boosts the immune system, via blocking the inhibitory Programmed cell death protein-1 (PD-1)/PD-L1 pathway, a manipulation previously shown to alleviate disease symptoms and pathology. An anti-CCR2 monoclonal antibody (αCCR2), was used to block the CCR2 axis in a protocol that partially eliminates monocytes from the circulation at the time of anti-PD-L1 antibody (αPD-L1) injection, and for the critical period of their recruitment into the brain following treatment.ResultsPerformance of DM-hTAU mice in short-term and working memory tasks, revealed that the beneficial effect of αPD-L1, assessed 1 month after a single injection, was abrogated following blockade of CCR2. This was accompanied by the loss of the beneficial effect on disease pathology, assessed by measurement of cortical aggregated human tau load using Homogeneous Time Resolved Fluorescence-based immunoassay, and by evaluation of hippocampal neuronal survival. Using both multiparametric flow cytometry, and Cytometry by Time Of Flight, we further demonstrated the accumulation of FOXP3+ regulatory CD4+ T cells in the brain, 12 days following the treatment, which was absent subsequent to CCR2 blockade. In addition, measurement of hippocampal levels of the T-cell chemoattractant, C-X-C motif chemokine ligand 12 (Cxcl12), and of inflammatory cytokines, revealed that αPD-L1 treatment reduced their expression, while blocking CCR2 reversed this effect.ConclusionsThe CCR2/CCL2 axis is required to modify pathology using PD-L1 blockade in a mouse model of tauopathy. This modification involves, in addition to monocytes, the accumulation of FOXP3+ regulatory CD4+ T cells in the brain, and the T-cell chemoattractant, Cxcl12.
| S-EPMC8234631 | biostudies-literature
Project description:ObjectiveTo show that for the MRI workup of non-specific low back pain and/or lumbar radiculopathy, the acquisition of T1-weighted sequences in the sagittal plane could be waived when using an FSE T2-weighted Dixon sequence.Materials and methodsThree musculoskeletal radiologists retrospectively reviewed fifty lumbar spine MRI examinations performed for non-specific low back pain and/or lumbar radiculopathy. Two protocols were separately analyzed in the sagittal plane: a standard protocol (T1-weighted, in-phase, and water-only images of an FSE T2-weighted Dixon sequence) and a simplified protocol (fat-only, in-phase, and water-only images of an FSE T2-weighted Dixon sequence). Eight items usually assessed on T1-weighted sequences were analyzed for each of the vertebrae (n?=?250), vertebral endplates (n?=?500), vertebral corners (n?=?1000), foramina (n?=?500), lamina (n?=?500), and facet joints (n =?500). Interchangeability of these protocols was tested using the individual equivalence index. A decrease in interobserver agreement of ??5% when one reader used the simplified protocol compared with when both readers used the standard protocol was considered clinically significant. Interreader and intrareader agreement were assessed using kappa statistics. Rates of findings with each protocol were compared using odd ratios.ResultsThe standard and simplified protocols were interchangeable (range of upper bound of the 95%CI of individual equivalence index?=?0.25 to 1.38%). Intraprotocol and interprotocol interreader kappa values were similar (0.253-0.671 vs. 0.236-0.723, respectively). Rates of findings were not statistically significantly different (p???0.074), or were higher with the simplified protocol (p???0.036).ConclusionIn our target population, a single sagittal T2-weighted Dixon sequence may replace the recommended combination of T1-, T2-, and fat-suppressed T2-weighted sequences.Key points• In patients with non-specific low back pain or lumbar radiculopathy, spine MRI in the sagittal plane could be limited to a single FSE T2-weighted Dixon sequence, hereby reducing the acquisition time. • A simplified protocol of spine MRI in the sagittal plane combining FSE T2-weighted Dixon sequence provides the same information as a standard protocol including T1-, T2-, and fat-suppressed T2-weighted sequences for the workup of degenerative lumbar spine lesions. • For some findings shown on the simplified protocol, such as focal bone marrow replacement lesions or signs of infection, additional sequences including pre- and post-contrast T1-weighted sequences may be required, as is currently the case when using the standard protocol.
| S-EPMC7160219 | biostudies-literature
Project description:IntroductionSurgical rates for low back pain (LBP) have been increasing in Europe, North America and Asia. Many patients treated surgically will require postsurgical rehabilitation. Little is known about the effectiveness of postsurgical rehabilitation interventions on health outcomes or about patients' experiences with these interventions.ObjectivesTo conduct a mixed studies systematic review of quantitative and qualitative studies regarding: (1) the effectiveness and safety of postsurgical rehabilitation interventions for adults with LBP treated surgically and (2) the experiences of patients, healthcare providers, caregivers or others involved with the rehabilitation.Methods and analysisWe will search MEDLINE, Embase, PsycINFO, CINAHL, the Index to Chiropractic Literature, the Cochrane Controlled Register of Trials and the Rehabilitation & Sports Medicine Source for peer-reviewed empirical studies published from inception in any language. Studies using quantitative, qualitative and mixed methodologies will be included. We will also search reference lists of all eligible articles. Data extraction will include type of presurgical pathology, indication for surgery, surgical procedure, how the intervention was delivered and by whom, context and setting. We will conduct a quality assessment of each study and consider study quality in our evidence synthesis. We will use a sequential approach at the review level to synthesise and integrate data. First, we will synthesise the quantitative and qualitative studies independently, conducting a meta-analysis of the quantitative studies if appropriate and thematic synthesis of the qualitative studies. Then, we will integrate the quantitative and qualitative evidence by juxtaposing the findings in a matrix.Ethics and disseminationEthical approval is not required for this knowledge synthesis. Findings will be disseminated through knowledge translation activities including: (1) presentations at national and international conferences and scientific meetings; (2) presentations to local and international stakeholders; (3) publications in peer-reviewed journals and (4) posts on organisational websites.Prospero registration numberCRD42019134607.
| S-EPMC7170616 | biostudies-literature
Project description:BACKGROUND:Although poor standing posture is a known cause of low back pain, the mechanisms involved are unclear. The aim of this study was to clarify the kinetic and posture angle features of standing posture that might influence low back pain. METHODS:Sixty-seven young men were enrolled in this cross-sectional case-control study and were categorized according to whether they did or did not have low back pain. Habitual standing posture was assessed in each group, using a three-dimensional motion analysis system, force plates, and a spinal mouse. Kinetic and posture angle factors were compared between participants with and without low back pain. The relationship between specific features of standing posture and low back pain was analyzed using logistic regression. RESULTS:The intervertebral disc compressive force and the low back moment were significantly greater in the group with low back pain than in the group without low back pain. The intervertebral disc compressive force was the factor most strongly associated with low back pain during static standing. CONCLUSIONS:Logistic regression analysis identified intervertebral disc compressive force as an independent variable associated with low back pain. This finding suggests that increased intervertebral disc compressive force may promote development of low back pain in standing posture.
| S-EPMC6298701 | biostudies-literature
Project description:We performed genome-wide DNA methylation analysis of 850,000 CpG sites in women and men with chronic Low Back Pain (LBP) and pain free-controls. T cells were isolated (Discovery Cohort, n=32) and used to identify differentially methylated CpG sites, and gene ontologies and molecular pathways were identified.T cells were isolated (Discovery Cohort, n=32) and used to identify differentially methylated CpG sites, and gene ontologies and molecular pathways were identified. A polygenic DNA methylation score for LBP was generated in both women and men. Validation was performed in an independent cohort (Validation Cohort, n=63) of chronic LBP and healthy controls. Analysis with the Discovery Cohort revealed a total of 2,496 and 419 differentially methylated CpGs in women and men, respectively. The majority of these sites were hypo-methylated in women and enriched in genes with functions in the extracellular matrix, the immune system (i.e. cytokines) or in epigenetic processes. In men, we identified a unique chronic LBP DNA methylation signature characterized by significant enrichment for genes from the major histocompatibility complex. A sex-specific polygenic DNA methylation score was generated to evaluate the pain status of each individual and confirmed in The Validation Cohort using pyrosequencing.
2021-11-10 | GSE162350 | GEO