| 1. |
- Barreto Henriksson, Helena, et al.
(författare)
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Support of Concept that Migrating Progenitor Cells from Stem Cell Niches Contribute to Normal Regeneration of the Adult Mammal Intervertebral Disc: A Descriptive study in the New Zeeland white Rabbit.
- 2012
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Ingår i: Spine. - 0362-2436 .- 1528-1159. ; 37:9
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Study Design. Descriptive experimental study performed in rabbits of two age groups.Objective. To study and investigate presence of prechondrocytic cells and cell migration routes in the IVD region, to gain knowledge about the normal IVD regeneration pattern.Summary of Background Data. Disc degeneration is believed to play a major role in patients with chronic lumbar pain. Regeneration processes and cell migration within the intervertebral disc (IVD) have been sparsely described. Therefore it is of interest to increase knowledge of these processes in order to understand pathological conditions of the IVD.Methods. 5-bromo-2-deoxyuridine (BrdU) in vivo labelling was performed in two groups of rabbits, 3 and 9 months old at the beginning of the experiment, in total 27 rabbits. BrdU is incorporated into DNA during mitosis and then it is gradually diluted with each cell division until it finally disappears. Incorporation of BrdU was then visualized by immunohistochemistry (IHC) at different time points providing cell division pattern and presence of slow-cycling cells in the IVD region. IVD tissue was investigated by IHC for: Growth- and differentiation-factor-5 (GDF5), SOX9 (chondrogenic lineage markers), SNAIL homolog1 (SNAI1), SNAIL homolog2 (SLUG)(migration markers) and β1-INTEGRIN (cellular adhesion marker). In addition, GDF5, SOX9 and BMPRIB expression were investigated on genetic level.Results. BrdU+ cells were observed in early time points in the IVD niche, adjacent to the epiphyseal plate, at later time points mainly in outer region of the annulus fibrosus (AF) for both age groups of rabbits, indicating a gradual migration of cells. The presence of SLUG, SNAI1, GDF5, SOX9 and β1-INTEGRIN were found in same regions.Conclusion. The results suggest a cellular migration route from the IVD stem cell niche toward the AF and the inner parts of the IVD. These findings may be of importance for understanding IVD regenerative mechanisms and for future development of biological treatment strategies.
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| 2. |
- Barreto Henriksson, Helena, et al.
(författare)
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Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model.
- 2009
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Ingår i: Spine. - 1528-1159. ; 34:2, s. 141-8
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: Experimental and descriptive study of a xenotransplantation model in minipigs. OBJECTIVE: To study survival and function of human mesenchymal stem cells (hMSCs) after transplantation into injured porcine spinal discs, as a model for cell therapy. SUMMARY OF BACKGROUND DATA: Biologic treatment options of the intervertebral disc are suggested for patients with chronic low back pain caused by disc degeneration. METHODS: Three lumbar discs in each of 9 minipigs were injured by aspiration of the nucleus pulposus (NP), 2 weeks later hMSCs were injected in F12 media suspension (cell/med) or with a hydrogel carrier (Puramatrix) (cell/gel). The animals were sacrificed after 1, 3, or 6 months. Disc appearance was visualized by magnetic resonance imaging. Immunohistochemistry methods were used to detect hMSCs by antihuman nuclear antibody staining, and further performed for Collagen II, Aggrecan, and Collagen I. SOX 9, Aggrecan, Versican, Collagen IA, and Collagen IIA and Collagen IIB human mRNA expression was analyzed by real-time PCR. RESULTS: At magnetic resonance imaging all injured discs demonstrated degenerative signs. Cell/gel discs showed fewer changes compared with cell/med discs and only injured discs at later time points. hMSCs were detected in 9 of 10 of the cell/gel discs and in 8 of 9 of the cell/med discs. Immunostaining for Aggrecan and Collagen type II expression were observed in NP after 3 and 6 months in gel/cell discs and colocalized with the antihuman nuclear antibody. mRNA expression of Collagen IIA, Collagen IIB, Versican, Collagen 1A, Aggrecan, and SOX9 were detected in both cell/med and cell/gel discs at the time points 3 and 6 months by real-time PCR. CONCLUSION: hMSCs survive in the porcine disc for at least 6 months and express typical chondrocyte markers suggesting differentiation toward disc-like cells. As in autologous animal models the combination with a three-dimensional-hydrogel carrier seems to facilitate differentiation and survival of MSCs in the disc. Xenotransplantation seems to be valuable in evaluating the possibility for human cell therapy treatment for intervertebral discs.
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| 3. |
- Brisby, Helena, 1965, et al.
(författare)
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In vivo measurement of facet joint nitric oxide in patients with chronic low back pain.
- 2007
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Ingår i: Spine. - 1528-1159. ; 32:14, s. 1488-92
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Tidskriftsartikel (refereegranskat)abstract
- Prospective case-control study testing a new diagnostic method.The aim of the present study was to investigate the concentration of nitric oxide (NO) in the perifacetal region in patients with chronic low back pain and healthy controls.Facet joint arthrosis may be a pain source in chronic back pain. Increased concentrations of NO, an oxygen-free radical, have been demonstrated in temporomandibular and knee joints with osteoarthritis.Patients with at least 6 months' duration of chronic low back pain and signs of facet joint osteoarthrosis (n = 24) and healthy volunteers (n = 7) were included. A detailed questionnaire, including visual analogue scale, was completed before and 6 weeks after the measurements. NO was measured with a custom-designed electrochemical real-time NO sensor inserted under fluoroscopic guidance. All patients received corticosteroids and local anesthetics after NO measurements.NO measurements were obtained from all participants. No adverse effects were noted. The patients with chronic low back pain demonstrated higher concentrations of NO in the perifacetal region compared with healthy controls (1.66 +/- 0.28 vs. 0.46 +/- 0.14 nmol/L, P = 0.007). No association between NO concentration and pain duration or pain level was detected. Patients with a positive response to local anesthetics and corticosteroid injection (defined as a >or=20 mm reduction of visual analogue scale at the 6-week follow-up visit) had higher NO concentrations than patients without positive response.The study demonstrates that it is feasible and safe to measure NO with a real time-sensor in or around the facet joints. The findings of higher concentrations of NO in the perifacetal region in chronic low back patients compared with healthy controls indicate that the degenerative process of the joints in these patients may cause increased NO production. The observation of higher NO concentrations in the perifacetal region in patients responding to corticosteroid/local anesthetic infiltration indirectly suggest a more pronounced inflammatory process in these patients.
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| 4. |
- Brisby, Helena, 1965, et al.
(författare)
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Thalamic activation in a disc herniation model.
- 2007
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Ingår i: Spine. - 1528-1159. ; 32:25, s. 2846-52
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: A novel approach combining a rodent disc herniation model with electrophysiologic recordings of thalamic evoked responses. OBJECTIVE: To assess short-term effects of nucleus pulposus (NP) application on dorsal root ganglions (DRG) on high threshold afferent fiber evoked activation in the thalamus. SUMMARY OF BACKGROUND DATA: Epidural application of NP in combination with mechanical compression induces pain related behavior in rats associated with enhanced activity of pain-processing neurons in the dorsal horn of the spinal cord. However, possible effects on neuronal activity in the pain processing ventral posterior lateral (VPL) thalamic nucleus following NP application on DRG have not been investigated. METHODS: Responses in the contralateral VPL evoked by electrical stimulation of the sciatic nerve and of the fourth lumbar (L4) DRG were recorded in adult Sprague-Dawley rats. Records were obtained before and during application (5, 10, and 20 minutes) of NP or of adipose tissue (AT) to the L4 DRG. AT was used as control for mechanical effects of NP application. RESULTS: Application of NP resulted in an increase of evoked thalamic responses to 138% +/- 10% of control after 20 minutes (P < 0.01), whereas AT application for 20 minutes resulted in a reduction of evoked responses to 77% +/- 4% (P < 0.05). Recordings in control animals (i.e., with no application) demonstrated stable evoked neuronal thalamic activity for up to 40 minutes. CONCLUSION: The study demonstrates that NP application onto DRG increases afferent fiber evoked responses in the thalamus and in view of the opposite effects of AT application suggests that these effects may be specific for NP. The results show that NP affects sensory transmitting pathways within a few minutes, possibly due to rapid and reversible alterations in the neuronal excitability. The study thus introduces a rodent model for studying sensory afferent evoked thalamic activity related to DRG injury which may be used to evaluate analgesics and anti-inflammatory drugs used for pain relief in disc herniation and neuropathic pain patients.
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| 5. |
- Brisby, Helena, 1965, et al.
(författare)
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The effect of running exercise on intervertebral disc extracellular matrix production in a rat model
- 2010
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Ingår i: Spine. - 1528-1159. ; 35:15, s. 1429-1436
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: Using a running rat model, the effects of physical exercise on cellular function and intervertebral disc (IVD) extracellular matrix were studied. OBJECTIVE: To investigate whether 3-weeks treadmill running exercise can stimulate matrix production and cellular proliferation of the IVD. SUMMARY OF BACKGROUND DATA: Appropriate physical exercise plays an important role in the treatment of patients with low back pain-associated IVD disorder. However, it is unknown how regular exercise affects the disc at the cellular level. METHODS: Twelve Sprague-Dawley rats underwent a daily treadmill exercise regime for a total of 3 weeks. Twelve nonexercised rats served as controls. The spinal lumbar IVD were collected and paraffin embedded for histologic analysis. Cell counts were determined on hematoxylin-eosin- and Masson-Trichrome-stained paraffin sections. Protein expression of collagen-I, collagen-II, aggrecan, Sox-9, and Sox-6 was evaluated with immunohistochemical staining. mRNA expression of Sox-9 and collagen-2 were studied by in situ hybridization. Proteoglycans were visualized with Alcian blue. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. RESULTS: The cell numbers in the anulus fibrosus (AF) increased by 25% (P < 0.05) after 3 weeks of exercise. Collagen-2 and Sox-9 mRNA were strongly expressed in the nucleus pulposus (NP) samples of the running group, but weakly expressed in the controls. An increase in collagen-II, aggrecan, and Sox-9 protein expression in NP and AF regions of the disc was detected in the exercised rats compared with controls. Quantification of Alcian blue staining demonstrated increased proteoglycan in both NP (8-fold) and AF (7-fold) in the exercised group compared with controls (P < 0.05). In addition, no significant differences were observed between the experimental groups in cellular apoptosis, collagen-I, or Sox-6 expression. CONCLUSION: In this study, increased extracellular matrix production and cell proliferation with no induction of disc cell apoptosis was observed in the lumbar IVD after a 3-week running regimen in rats, suggesting that regular exercise may have an augmentative effect on cells and matrix production.
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| 6. |
- Carling, Malin S, et al.
(författare)
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Preoperative Fibrinogen Plasma Concentration Is Associated With Perioperative Bleeding and Transfusion Requirements in Scoliosis Surgery.
- 2011
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Ingår i: Spine. - 1528-1159. ; 36:7, s. 549-55
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN.: Prospective observational study. OBJECTIVE.: To investigate the potential association between fibrinogen, bleeding, and transfusion requirements after scoliosis surgery. SUMMARY OF BACKGROUND DATA.: Bleeding complications during and after orthopedic surgery are associated with increased morbidity and mortality. Early identification of patients with increased risk of excessive bleeding offers the possibility to initiate countermeasures. Fibrinogen is a key protein in the coagulation cascade, and thus a potential biomarker for bleeding risk. METHODS.: A total of 82 otherwise healthy patients (mean age: 15 ± 3 years, 85% girls) undergoing surgery for adolescent idiopathic scoliosis were included in the study. Patient variables (age, gender, operation time, and thrombosis prophylaxis), preoperative laboratory variables (hemoglobin, platelet count, activated partial thromboplastin time [aPTT], prothrombin time [PT], and fibrinogen), peroperative and postoperative bleeding volume, and transfusions were registered. Correlations between laboratory variables and bleeding volume were calculated with Pearson test. Patient variables and laboratory variables were compared with Student t test between patients with bleeding volume in the upper quartile ("bleeders") and the remaining patients, and between patients with extensive transfusion (defined as >2 U of packed red cells) and no or limited transfusions (≤2 U). RESULTS.: Mean fibrinogen concentration was 3.0 ± 0.7 g/L (range, 1.3-4.9). Mean total perioperative bleeding volume was 1552 ± 1019 mL (range, 100-5800 mL). Total bleeding volume correlated significantly with preoperative fibrinogen concentration (r = -0.31, P = 0.005) but neither with platelet count, aPTT, nor PT (P = 0.61, 0.46, and 0.57, respectively). Bleeders had significantly lower preoperative fibrinogen plasma concentration (2.6 ± 0.6 vs. 3.1 ± 0.6 g/L, P = 0.002). Of total, 16% (13/82) of the patients were transfused with >2 U of packed red cells.Patients with extensive transfusions had significantly lower preoperative fibrinogen plasma concentration (2.5 ± 0.7 vs. 3.1 ± 0.6 g/L, P = 0.002), while preoperative platelet count, aPTT, and PT did not differ. CONCLUSION.: The results indicate that preoperative fibrinogen concentration is a limiting factor for postoperative hemostasis during and after scoliosis surgery. Preoperative measurement of fibrinogen concentration provides more information about bleeding volume and transfusion requirements than standard screening tests.
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| 7. |
- Cornefjord, M., et al.
(författare)
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Cerebrospinal fluid biomarkers in experimental spinal nerve root injury
- 2004
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Ingår i: Spine. - 1528-1159. ; 29:17, s. 1862-8
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: Cerebrospinal fluid biomarkers were evaluated in a setup using established pig models to mimic clinical disc herniation. OBJECTIVES: To investigate biomarkers for nerve tissue injury, inflammation, and pain in cerebrospinal fluid after mechanical compression and/or nucleus pulposus application to spinal nerve roots. SUMMARY OF BACKGROUND DATA: The association between mechanical compression, biochemical effects of nucleus pulposus, and nerve root injury in degenerative disc disorders is incompletely investigated. METHODS: The unilateral S1 nerve root was exposed in 20 pigs. The animals were divided into four groups (n = 5 each): 1) slow-onset mechanical compression with an ameroid constrictor; 2) autologous nucleus pulposus application; 3) mechanical compression plus nucleus pulposus; and 4) sham operation. After 1 week, 6 mL of cerebrospinal fluid was collected, and four structural nerve proteins, neurofilaments, S-100, glial fibrillary acidic protein, neuron-specific enolase, the proinflammatory cytokine interleukin-8, the neurotransmitter nociceptin, and substance P endopeptidase activity were analyzed using immunoassays. RESULTS: The concentration of neurofilament was increased in the mechanical compression group (17.0 microg/L +/- 5.0) and in the mechanical compression plus nucleus pulposus group (19.8 +/- 12.1 microg/L) compared with the sham group (0.9 +/- 0.9 microg/L) and the nucleus pulposus group (0.4 +/- 0.1 microg/L) (P < 0.01 for both). The concentration of nociceptin was increased significantly in the mechanical compression group (24.0 +/- 8.6 fm/mL) and in the mechanical compression plus nucleus pulposus group (31.2 +/- 6.6 fm/mL) compared with the sham group (7.0 +/- 1.3 fm/mL) (P < 0.05 and P < 0.01, respectively). A correlation was found between concentrations of neurofilament and nociceptin (r = 0.50, P < 0.05). There were no intergroup differences regarding glial fibrillary acidic protein, neuron-specific enolase, S-100, interleukin-8, or substance P endopeptidase activity. CONCLUSIONS: The present study demonstrates increased concentrations of neurofilament and nociceptin in cerebrospinal fluid after nerve root compression. A simultaneous application of nucleus pulposus did not increase the response.
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| 8. |
- Eriksson, Stefanie, et al.
(författare)
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Texture Analysis of Magnetic Resonance Images Enables Phenotyping of Potentially Painful Annular Fissures.
- 2022
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Ingår i: Spine. - 1528-1159. ; 47:5, s. 430-437
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Tidskriftsartikel (refereegranskat)abstract
- Retrospective analysis of prospectively collected data.To investigate whether intervertebral disc (IVD) image features, extracted from magnetic resonance (MR) images, can depict the extension and width of annular fissures and associate them to pain.Annular fissures are suggested to be associated with low back pain (LBP). Magnetic resonance imaging (MRI) is a sensitive method, yet fissures are sometimes unobservable in T2-weighted MR-images, even though fissure information is present in the image. Image features can mathematically be calculated from MR-images and might reveal fissure characteristics.44 LBP patients who underwent MRI, low-pressure discography (<50psi) and computed tomography (CT) sequentially in one day, were reviewed. After semi-automated segmentation of 126 discs, image features were extracted from the T2-weighted images. The number of image features were reduced with principle component analysis (PCA). CT-discograms were graded and dichotomized regarding extension and width of fissures. IVDs were divided into fissures extending to outer annulus vs. short/no fissures. Fissure width was dichotomized into narrow (<10%) vs. broad fissures (>10%), and into moderately broad (10%-50%) vs. very broad fissures (>50%). Logistic regression was performed to investigate if image features could depict fissure extension to outer annulus and fissure width. As a sub-analysis, the association between image features used to depict fissure characteristics and discography-provoked pain-response were investigated.Fissure extension could be depicted with sensitivity/specificity = 0.97/0.77 and area under curve (AUC) = 0.97. Corresponding results for width depiction were sensitivity/specificity = 0.94/0.39 and 0.85/0.62, and AUC = 0.86 and 0.81 for narrow vs. broad and moderately broad vs. very broad fissures respectively. Pain prediction with image features used for depicting fissure characteristics showed sensitivity/specificity = 0.90/0.36, 0.88/0.4, 0.93/0.33; AUC = 0.69, 0.75 and 0.73 respectively.Standard MR-images contains fissure information associated to pain that can be depicted with image features, enabling non-invasive phenotyping of potentially painful annular fissures.Level of Evidence: 2.
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| 9. |
- Rönnberg, Katarina, 1969, et al.
(författare)
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Patients' satisfaction with provided care/information and expectations on clinical outcome after lumbar disc herniation surgery
- 2007
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Ingår i: Spine. - : Ovid Technologies (Wolters Kluwer Health). - 0362-2436 .- 1528-1159. ; 32:2, s. 256-261
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN. A prospective study of patients undergoing lumbar disc herniation surgery. OBJECTIVES. To assess patients' satisfaction with care/preoperative information, if expectations on surgical results and ability to return to work are related to baseline characteristics, and/or can predict self-reported outcome. Self-reported outcome was compared with objective outcome. SUMMARY OF BACKGROUND DATA. Patients' expectations on treatment results have been discussed as a predictive factor for postoperative outcome and satisfaction demonstrated to be directly related to patient expectations. METHODS. The study includes 148 patients, 46% women, mean age 40 (range 18-66). Before and 2 years after surgery, questionnaires about given information/care, expected/present work ability, and expectations on/obtained improvement of physical functions/symptoms (leg and back pain, sensibility, and muscle function) were filled in. The visual analog scale leg pain, Zung Depression Scale, and Oswestry Disability Index were used as baseline characteristics. At 2-year follow-up, self-reported and objective outcome was assessed. RESULTS. Satisfaction with given information/care were reported by 46% and 82%, respectively. Zung Depression Scale related to expectations on leg pain recovery (P = 0.022), work ability (P = 0.046), and satisfaction with given information (P = 0.031). Patients who expected to return (76%) and not return (24%) to work, returned in 78% and 26%, respectively (P = 0.021). A high agreement between self-reported outcome and objective outcome were found (P < 0.001). CONCLUSIONS. Patients undergoing lumbar disc herniation surgery are mostly satisfied with provided care before and after surgery, however, less satisfied with information provided. Further, patients with preoperative positive expectations on work return and realistic expectations on pain and physical recovery have a greater chance to be satisfied with the surgical results. © 2007 Lippincott Williams & Wilkins, Inc.
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| 10. |
- Torén, Leif, et al.
(författare)
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MRI During Spinal Loading Reveals Intervertebral Disc Behavior Corresponding to Discogram Findings of Annular Fissures and Pain Provocation. : Torén L, Lagerstrand K, Waldenberg C, Brisby H, Hebelka H.
- 2020
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Ingår i: Spine. - 0362-2436 .- 1528-1159. ; 45:22, s. E1500-E1506.
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Tidskriftsartikel (refereegranskat)abstract
- Study design: Retrospective analysis of prospectively collected data. Objective: The aim of this study was to investigate whether spinal loading, depicted with magnetic resonance imaging (MRI), induces regional intervertebral disc (IVD) differences associated with presence and width of annular fissure and induced pain at discography. Summary of background data: Annular fissures play a role in low back pain (LBP) but cannot be accurately characterized with conventional MRI. Recently, annular fissures were suggested to influence different load-induced IVD behavior during MRI when comparing LBP-patients and controls. Thus, the loading effect could characterize behavior related to annular fissures noninvasively with MRI. Methods: Lumbar spines of 30 LBP-patients were investigated with MRI with and without loading, discography and CT. Five IVD regions were outlined on sagittal MRI images. Difference in normalized signal intensity (SI) with and without loading was calculated for each region. Eighty-three CT-discograms were graded regarding presence and width of fissures. Discograms were classified as pain-positive if a concordant pain response was obtained at a pressure <50 psi. Results: Comparing IVDs with outer fissures with IVDs without fissures, loading induced different behavior in the two ventral regions and in the posterior region. Higher SI increase in the central region was induced in IVDs with narrower fissures compared to IVDs with wider fissures. In the group of pain-negative discograms, a SI decrease was induced in the dorsal region whereas lack of such in the pain-positive group. Conclusion: The spinal loading-effect, depicted with MRI, reveals different regional behaviors between IVDs with outer fissures compared to those without, and between IVDs with narrow and broad fissures, as well as within posterior annulus between pain-positive and pain-negative discograms. Findings are of importance for future attempts to uncover phenotypes of painful IVDs.
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