Intra-articular collagenase in the spinal facet joint induces pain, DRG neuron dysregulation and increased MMP-1 absent evidence of joint destruction
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ABSTRACT:
SUBMITTER: Ita M
PROVIDER: S-EPMC7738551 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:This study aimed to demonstrate the effect of intra-articular (IA) lumbar facet joint (LFJ) pulsed radiofrequency (PRF) for the management of LFJ pain, and to compare the effect of IA LFJ PRF to IA corticosteroid injection (ICI). Pathology in the LFJ is a common source of lower back pain (LBP). It is responsible for chronic LBP in approximately 15% to 45% of patients. It has been reported that PRF stimulation can effectively reduce refractory joint pain.Sixty patients with LFJ pain were recruited and randomly assigned to 1 of 2 groups: the IA PRF group and the ICI group. There were 30 patients in each group. At pretreatment, 2 weeks, 1, 3, and 6 months after treatment, we assessed the severity of LBP using a numeric rating scale (NRS).Compared with the pretreatment NRS scores, patients in both groups showed a significant decrease in NRS scores at 2 weeks, and 1, 3, and 6 months after each treatment. Between groups, changes in the NRS scores were significantly different over time. At 2 weeks and 1 month after each procedure, the NRS score after ICI was significantly lower than that after the PRF stimulation. However, at 3 and 6 months after the procedures, the decrements of NRS scores were not significantly different between the 2 groups. Six months after treatment, about half of patients in both groups reported successful pain relief (pain relief of ?50%).In the current study, both IA PRF stimulation and ICI into the LFJ significantly relieved LFJ pain. Their effects persisted for at least 6 months after the procedure. Thus, IA PRF is a useful therapeutic option for the management of LFJ pain.
| S-EPMC5380295 | biostudies-other
Project description:Facet joint osteoarthritis (FJOA) is a common degenerative joint disorder with high prevalence in the elderly. FJOA causes lower back pain and lower extremity pain, and thus severely impacts the quality of life of affected patients. Emerging studies have focused on the histomorphological and histomorphometric changes in FJOA. However, the dynamic genetic changes in FJOA have remained to be clearly determined. In the present study, previously obtained RNA deep sequencing data were subjected to an ingenuity pathway analysis (IPA) and canonical signaling pathways of differentially expressed genes (DEGs) in FJOA were studied. The top 25 enriched canonical signaling pathways were identified and canonical signaling pathways with high absolute values of z-scores, specifically leukocyte extravasation signaling, Tec kinase signaling and osteoarthritis pathway, were investigated in detail. DEGs were further categorized by disease, biological function and toxicity (tox) function. The genetic networks between DEGs as well as hub genes in these functional networks were also investigated. It was demonstrated that C-X-C motif chemokine ligand 8, elastase, neutrophil expressed, growth factor independent 1 transcriptional repressor, Spi-1 proto-oncogene, CCAAT enhancer binding protein epsilon, GATA binding protein 1, TAL bHLH transcription factor 1, erythroid differentiation factor, minichromosome maintenance complex component 4, BTG anti-proliferation factor 2, BRCA1 DNA repair-associated, cyclin D1, chromatin assembly factor 1 subunit A, triggering receptor expressed on myeloid cells 1 and tumor protein p63 were hub genes in the top 5 IPA networks (with a score >30). The present study provides insight into the pathological processes of FJOA from a genetic perspective and may thus benefit the clinical treatment of FJOA.
| S-EPMC7086291 | biostudies-literature
Project description:BackgroundThe spring ligament fibrocartilaginous complex (SLFC), which is essential for stabilizing the medial longitudinal arch, features a little-explored fibrocartilaginous facet within its superomedial aspect, articulating with the talar head. This research aimed to provide a detailed anatomical description of this facet, designated as the spring ligament articular facet (SLAF).MethodsNine normally aligned cadaveric lower limbs were dissected, approaching the SLFC from a superior direction. Following talus disarticulation, high-resolution images of the ligament complex were captured and analyzed. ImageJ software was used to determine the areas and dimensions of the superomedial calcaneonavicular (SMCN) spring and SLAF.ResultsThe fibrocartilage facet exhibited a trapezoid shape in all specimens. The mean area for SMCN spring was 280.39 mm², and for SLAF, it was 200 mm². The proximal-to-distal length for SLAF averaged 11.78 mm at its longest and 5.34 mm at its shortest. Attachment of the SLAF to the calcaneum and the navicular showed robust fibrous structures, with average measurements of 3.75 and 1.75 mm at the medial and lateral calcaneal margins, and 2.75 and 2.98 mm at the medial and lateral navicular margins, respectively.ConclusionThis study clearly delineated the individual structural components of the SLFC articulating with the talar head and detailed its dimensions, emphasizing the need for more specific anatomical terminology that respects the intricate anatomy of the SLFC.Level of evidenceLevel III, descriptive study.
| S-EPMC11348484 | biostudies-literature
Project description:Previously we showed that MMP-1 (collagenase-1) and MMP-13 (collagenase-3) differentially regulate the expression of osteoblastic markers in a heterogenous population of primary human periodontal ligament cells. The mechanisms for these differential responses are not known, but may result from divergence in regulation of early osteogenic transcription factors. The purpose of this study was to elucidate where in the hierarchy of osteoblast-specific transcription factors and markers the differences in MMP-1- and -13-mediated regulation of osteoblastic differentiation arise. We found that the overexpression of MMP-1 resulted in significant decreases in BMP-2, Dlx5, AP, OP and BSP and increases in TGF-β1 and MSX2. In contrast, MMP-13 overexpression resulted in significant decreases in Runx2, OP and BSP, and increases in TGF-β1, MSX2 and OC. The knockdown of MMP-1 caused significant increases in all osteoblastic markers. MMP-13 knockdown produced significant increases only in TGF-β1, MSX2 and Osx, but decreases in Runx2 and OC. Suppression of both MMPs together resulted in significant increases of all osteoblastic markers except Runx2. MMP-1 had a more robust and generalized effect in regulating osteoblast transcription factors and markers than MMP-13. Finally, of the markers and transcription factors assayed, Runx2 is the most early stage transcription factor induced by suppression of MMP-1, while Osx and MSX2 are the most early stage transcription factors regulated by MMP-13. These data show that MMP-1's and -13's differential regulation of osteoblastic markers in MG63 cells likely results from their modulation of divergent signaling pathways involved in osteoblastic differentiation.
| S-EPMC3116144 | biostudies-literature
Project description:Lumbar zygapophyseal joints act as primary pain generators in at least 10-15% of patients with chronic low back pain.Diagnostic nerve blocks are the most reliable way to diagnose lumbar zygapophyseal joint pain.IASP recommends either controlled or comparative blocks for diagnosis of zygapophyseal joint pain as there is a significant incidence of false positives with single blocks.Management should be multimodal comprising education, exercises, analgesics and procedural interventions to achieve functional restoration.There is a need for further RCTs with standardised diagnostic criteria and outcome measures as well as long-term data to determine the efficacy of radiofrequency denervation.
| S-EPMC4589934 | biostudies-other
Project description:ObjectiveOsteoarthritis is a degenerative joint disease whose molecular mechanism is currently unknown. Wnt/beta-catenin signaling has been demonstrated to play a critical role in the development and function of articular chondrocytes. To determine the role of beta-catenin signaling in articular chondrocyte function, we generated Col2a1-ICAT-transgenic mice to inhibit beta-catenin signaling in chondrocytes.MethodsThe expression of the ICAT transgene was determined by immunostaining and Western blot analysis. Histologic analyses were performed to determine changes in articular cartilage structure and morphology. Cell apoptosis was determined by TUNEL staining and the immunostaining of cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) proteins. Expression of Bcl-2, Bcl-x(L), and Bax proteins and caspase 9 and caspase 3/7 activities were examined in primary sternal chondrocytes isolated from 3-day-old neonatal Col2a1-ICAT-transgenic mice and their wild-type littermates and in primary chicken and porcine articular chondrocytes.ResultsExpression of the ICAT transgene was detected in articular chondrocytes of the transgenic mice. Associated with this, age-dependent articular cartilage destruction was observed in Col2a1-ICAT-transgenic mice. A significant increase in cell apoptosis in articular chondrocytes was identified by TUNEL staining and the immunostaining of cleaved caspase 3 and PARP proteins in these transgenic mice. Consistent with this, Bcl-2 and Bcl-x(L) expression were decreased and caspase 9 and caspase 3/7 activity were increased, suggesting that increased cell apoptosis may contribute significantly to the articular cartilage destruction observed in Col2a1-ICAT-transgenic mice.ConclusionInhibition of beta-catenin signaling in articular chondrocytes causes increased cell apoptosis and articular cartilage destruction in Col2a1-ICAT- transgenic mice.
| S-EPMC2667964 | biostudies-literature
Project description:ObjectiveRebamipide has antioxidant effects and is a drug with a local rather than systemic mechanism of action. Oxidative stress and inflammation in chondrocytes are the major factors contributing to the development and progression of osteoarthritis (OA). Since OA is mainly developed in weight bearing or overused joints, the locally sustained therapy is effective for targeting inflammatory component of OA. We investigated the effects of intra-articular injection of rebamipide loaded nanoparticles (NPs) in OA rat model.DesignWe fabricated rebamipide-loaded methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-PDLLA) and poly(D, L-lactide-co-glycolide) (PLGA) NPs that allow the sustained release of rebamipide. In vitro, chondrocytes from rat were used to investigate the cytotoxicity and anti-inflammatory effect of rebamipide-loaded NPs. In vivo, monosodium iodoacetate (MIA)-induced OA rats were divided into 7 groups, consisting of healthy control rats and rats injected with MIA alone or in combination with NPs, rebamipide (1 mg)/NPs, rebamipide (10 mg)/NPs, rebamipide (10 mg) solution, or oral administration.ResultsIn vitro, rebamipide/NPs dose-dependently suppressed the mRNA levels of pro-inflammatory mediators, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, matrix metalloproteinase (MMP)-3, MMP-13, and cyclo-oxygenase-2. In vivo, the mRNA levels of pro-inflammatory components most markedly decreased in the intra-articularly injected rebamipide (10 mg)/NP group compared to other groups. Macroscopic, radiographic, and histological evaluations showed that the intra-articular injection of rebamipide/NPs inhibited cartilage degeneration more than rebamipide solution or rebamipide administration.ConclusionsUsing a chemically induced rat model of OA, intra-articular delivery of rebamipide was associated with decreased local and systemic inflammatory response decreased joint degradation and arthritic progression.
| S-EPMC9137306 | biostudies-literature
Project description:IntroductionLumbar pain of facet origin is a common problem worldwide. For those patients not responding to traditional treatment, one approach may be intra-articular infiltration of corticoid and anaesthetic. However, despite the increasing demand for this procedure, no consensus exists regarding its therapeutic value. The selection of eligible participants may be a determining factor since only those with an inflammatory process will benefit from the use of corticosteroids. This study aims to identify differences in disability, pain and quality of life scores in individuals with and without facet joint inflammation who were diagnosed using MRI.Method and analysisThis prospective cohort will include individuals older than 18 years with a clinical diagnosis of facet syndrome who underwent intra-articular infiltration. Changes in scores of pain, disability and quality of life questionnaires at 1, 3, 6 and 12 months of follow-up compared with baseline will be analysed. An MRI examination performed before infiltration will help to distinguish between exposed (with inflammation) and non-exposed (non-inflammation) groups with facet syndrome. The primary outcome will be the disability questionnaire (Roland Morris), and the secondary outcomes will be the score questionnaires for pain (Visual Analogue Scale), quality of life (EuroQol Quality of Life Questionnaire) and disability (Oswestry).Ethics and disseminationThe Internal Review Board approved this study, which started only after the approval number (5291417.0.0000.0071) was received. All recruited participants will receive a verbal explanation about the purpose of the study, and their decision to participate will be free and voluntary. All participants enrolled in the study will provide a signed informed consent form including confidentiality terms. The results obtained in this study will be presented at national and international conferences and published in peer-reviewed scientific journals to disseminate the knowledge.Trials registration numberNCT03304730; Pre-results.
| S-EPMC6624116 | biostudies-literature
Project description:BACKGROUND:This study was performed to investigate the association between lumbar disc herniation (LDH) and facet joint osteoarthritis (FJOA) using magnetic resonance imaging (MRI). METHODS:Between March 2012 and September 2018, a total of 441 segments from 394 patients with LDH were included in the study. LDH was classified according to the Michigan State University (MSU) classification, in which the degree of LDH is divided into 3 levels (expressed as 1, 2, and 3) and the location of LDH is divided into 4 zones (described as A, AB, B, and C). Bilateral FJOA was graded from 0 to 3 using the criteria introduced by Weishaupt et al., and bilateral facet orientations were measured on axial MRI slices. A mixed-effects ordinal logistic regression model was utilized to determine the potential factors that may be associated with FJOA, including sex, age, body mass index (BMI), segment, facet orientation and tropism, and the degree and location of LDH. RESULTS:In general, the prevalence of FJOA (grade???2) was 66.2% in LDH segments. For both the left and right sides, the degree of LDH was associated with the severity of FJOA (p?<?0.01). Age and BMI were also associated with the severity of left and right FJOA (p?=?0.002 and p <?0.001 for age, p <?0.001 and p?=?0.003 for BMI, respectively), while segment, facet orientation, and facet tropism were not (p?>?0.05 for all). Notably, MSU-B LDH was associated with greater odds of having more severe FJOA on the herniation side (left: p <?0.001, odds ratio (OR)?=?2.714, 95% confidence interval (CI)?=?1.583~4.650; right: p?=?0.003, OR?=?2.615, 95% CI?=?1.405~4.870). However, other locations of LDH were not associated with the severity of FJOA (p?>?0.05 for all). CONCLUSIONS:Both the degree of LDH and MSU-B LDH are associated with the severity of FJOA. The association between LDH and FJOA highlights the complexity of the etiology of FJOA.
| S-EPMC6990568 | biostudies-literature
Project description:Bladder small DRG neurons, which are putative nociceptors pivotal to urinary bladder function, express more than a dozen different ionic membrane mechanisms: ion channels, pumps and exchangers. Small-conductance Ca2+-activated K+ (SKCa) channels which were earlier thought to be gated solely by intracellular Ca2+ concentration ([Ca]i) have recently been shown to exhibit inward rectification with respect to membrane potential. The effect of SKCa inward rectification on the excitability of these neurons is unknown. Furthermore, studies on the role of KCa channels in repetitive firing and their contributions to different types of afterhyperpolarization (AHP) in these neurons are lacking. In order to study these phenomena, we first constructed and validated a biophysically detailed single compartment model of bladder small DRG neuron soma constrained by physiological data. The model includes twenty-two major known membrane mechanisms along with intracellular Ca2+ dynamics comprising Ca2+ diffusion, cytoplasmic buffering, and endoplasmic reticulum (ER) and mitochondrial mechanisms. Using modelling studies, we show that inward rectification of SKCa is an important parameter regulating neuronal repetitive firing and that its absence reduces action potential (AP) firing frequency. We also show that SKCa is more potent in reducing AP spiking than the large-conductance KCa channel (BKCa) in these neurons. Moreover, BKCa was found to contribute to the fast AHP (fAHP) and SKCa to the medium-duration (mAHP) and slow AHP (sAHP). We also report that the slow inactivating A-type K+ channel (slow KA) current in these neurons is composed of 2 components: an initial fast inactivating (time constant ? 25-100 ms) and a slow inactivating (time constant ? 200-800 ms) current. We discuss the implications of our findings, and how our detailed model can help further our understanding of the role of C-fibre afferents in the physiology of urinary bladder as well as in certain disorders.
| S-EPMC6066259 | biostudies-literature