Annulus Fibrosus Injury Induces Acute Neuroinflammation and Chronic Glial Response in Dorsal Root Ganglion and Spinal Cord-An In Vivo Rat Discogenic Pain Model.

Chronic painful intervertebral disc (IVD) degeneration (i.e., discogenic pain) is a major source of global disability needing improved knowledge on multiple-tissue interactions and how they progress in order improve treatment strategies. This study used an in vivo rat annulus fibrosus (AF) injury-driven discogenic pain model to investigate the acute and chronic changes in IVD degeneration and spinal inflammation, as well as sensitization, inflammation, and remodeling in dorsal root ganglion (DRG) and spinal cord (SC) dorsal horn. AF injury induced moderate IVD degeneration with acute and broad spinal inflammation that progressed to DRG to SC changes within days and weeks, respectively. Specifically, AF injury elevated macrophages in the spine (CD68) and DRGs (Iba1) that peaked at 3 days post-injury, and increased microglia (Iba1) in SC that peaked at 2 weeks post-injury. AF injury also triggered glial responses with elevated GFAP in DRGs and SC at least 8 weeks post-injury. Spinal CD68 and SC neuropeptide Substance P both remained elevated at 8 weeks, suggesting that slow and incomplete IVD healing provides a chronic source of inflammation with continued SC sensitization. We conclude that AF injury-driven IVD degeneration induces acute spinal, DRG, and SC inflammatory crosstalk with sustained glial responses in both DRGs and SC, leading to chronic SC sensitization and neural plasticity. The known association of these markers with neuropathic pain suggests that therapeutic strategies for discogenic pain need to target both spinal and nervous systems, with early strategies managing acute inflammatory processes, and late strategies targeting chronic IVD inflammation, SC sensitization, and remodeling.

Tnfa , Il6 , Cxcl1 , and Adam8 Genes Are the Early Markers After Mouse Tail Intervertebral Disc Injury.

OBJECTIVES: The early molecular events after intervertebral disc injury remain unclear. In this study, we aimed to compare inflammatory markers from 1 day to 4 wks after injury to have a comprehensive understanding of the intervertebral disc response to injury. DESIGN: Mouse tail intervertebral disc injury was induced by a needle puncture. Inflammatory marker gene expression and morphological changes were recorded at 1 day, 1 wk, and 4 wks after injury. RESULTS: Tnfa , Il6 , and Cxcl1 gene expression peaked at day 1 post-needle puncture of the mouse intervertebral disc, Adam8 gene expression peaked at 1-wk time point, while Tipe2 gene expression was upregulated at week 4 postinjury. F4/80 positive cells, likely to be macrophages, are present as early as day 1 in the injured intervertebral discs and consistently present at week 4 postinjury. Loss of Safranin O staining and increased histological scores of the injured intervertebral discs are consistent with progressive degeneration after injury. CONCLUSIONS: Inflammatory cytokines including Tnfa precede Tipe2 , suggesting that Tipe2 is likely induced by Tnfa . Upregulation of Adam8 and Cxcl1 gene expression persisted at week 4, suggesting that they play a role in the transition to chronic phase of intervertebral disc degeneration.

Correction loss following short-segment posterior fixation for traumatic thoracolumbar burst fractures related to endplate and intervertebral disc destruction.

BACKGROUND: There has been widespread use of short-segment posterior fixation (SSPF) for traumatic thoracolumbar burst fractures. The relationship between the destruction of the vertebral endplate and adjacent disc and postoperative correction loss has been studied in only a few studies. This study investigated the risk factors for correction loss following SSPF. METHODS: Forty-eight patients (mean age 35.0 years) who underwent SSPF for thoracolumbar burst fractures were enrolled. The mean follow-up period was 25.7 months (12-98 months). The neurological status and postoperative back pain were assessed by the medical records. Segmental kyphotic angle (SKA) and anterior vertebral body height ratio (AVBHR) were measured radiographically to assess indirect vertebral body reduction and local kyphosis. Preoperative Sander's traumatic intervertebral disc lesion (TIDL) classification and AO classification were used to evaluate the severity of disc and vertebral endplate injury. The corrective loss was considered present if ΔSKA was ≥10°. A multivariate logistic regression analysis was performed to identify the risk factors associated with postoperative loss of correction. RESULTS: The fracture distribution was as follows: 10 at T12, 17 at L1, 10 at L2, 9 at L3, and 2 at L4. Vertebral fractures were classified in the following way: A3 in 13 patients, A4 in 11, B1 in 11, and B2 in 13. In 47 patients (98%), a union of the fractured vertebrae was achieved. SKA and AVBHR improved significantly after surgery from 11.6° to 3.5° and from 67.2 to 90.0%, respectively. However, the correction loss at follow-up was 10.4° and 9.7%, respectively. Twenty patients (42%) had severe TIDL (grade 3). Postoperative ΔSKA and ΔAVBHR were significantly higher in patients with TIDL grade 3 than with TIDL grade 0-2. The presence of cranial TIDL grade 3 and older age were significant risk factors for ΔSKA ≥10° on multivariate logistic regression analysis. All patients could walk at follow-up. TIDL grade 3 and ΔSKA ≥10° were associated with severe postoperative back pain. CONCLUSIONS: Risk factors for loss of correction after SSPF for thoracolumbar burst fractures were severe disc and endplate destruction at the time of injury and older age.

Effect of endplate reduction on endplate healing morphology and intervertebral disc degeneration in patients with thoracolumbar vertebral fracture.

OBJECTIVE: To determine the effect of endplate reduction on the final healing morphology and degenerative changes in intervertebral discs. METHODS: Forty-eight patients with single-level thoracolumbar fractures with endplate injury were included. All patients underwent posterior reduction and pedicle screw fixation, and postoperative imaging was used to determine whether endplate reduction was successful. The healing morphology of the endplate was divided into three types: increased endplate curvature, irregular healing and traumatic Schmorl node. MRI was performed at baseline and at the last follow-up evaluation to observe changes in disc degeneration (disc height and nucleus pulposus signal) and Modic changes. RESULTS: The reduction rate in the central area was significantly lower than that in the peripheral area (P = 0.017). In patients with successful reduction, 90.9% (20/22) of the endplates healed with increased curvature. In patients with an unsuccessful endplate reduction, 63.4% (26/41) of the endplates healed irregularly, and 34.1% (14/41) of the endplates formed traumatic Schmorl nodes. Endplate reduction was closely related to the final healing morphology of the endplate (P < 0.001), which had a significant protective effect on the degeneration of the intervertebral disc. At the last follow-up evaluation, there was no statistically significant correlation between different endplate healing morphologies and new Modic changes. CONCLUSIONS: The reduction rate in the central area is significantly lower than that in the peripheral area. Although all of the intervertebral discs corresponding to fractured endplates had degenerated to different degrees, successful endplate fracture reduction can obviously delay the degeneration of intervertebral discs.

Origin of M2 Mϕ and its macrophage polarization by TGF-ß in a mice intervertebral injury model.

INTRODUCTION: Studies have identified the presence of M1 and M2 macrophages (Mϕ) in injured intervertebral discs (IVDs). However, the origin and polarization-regulatory factor of M2 Mϕ are not fully understood. TGF-ß is a regulatory factor for M2 polarization in several tissues. Here, we investigated the source of M2 Mϕ and the role of TGF-ß on M2 polarization using a mice disc-puncture injury model. METHODS: To investigate the origin of M2 macrophages, 30 GFP chimeric mice were created by bone marrow transplantation. IVDs were obtained from both groups on pre-puncture (control) and post-puncture days 1, 3, 7, and 14 and CD86 (M1 marker)- and CD206 (M2 marker)-positive cells evaluated by flow cytometry (n = 5 at each time point). To investigate the role of TGF-ß on M2 polarization, TGF-ß inhibitor (SB431542) was also injected on post-puncture days (PPD) 5 and 6 and CD206 expression was evaluated on day 7 by flow cytometry (n = 5) and real time PCR (n = 10). RESULTS: The proportion of CD86+ Mϕ within the GFP+ population was significantly increased at PPD 1, 3, 7, and 14 compared to control. CD206-positive cells in GFP-populations were significantly increased on PPD 7 and 14. In addition, the percentage of CD206-positive cells was significantly higher in GFP-populations than in GFP+ populations. TGF-ß inhibitor reduced CD206-positive cells and Cd206 expression at 7 days after puncture. CONCLUSION: Our findings suggest that M2 Mϕ following IVD injury may originate from resident Mϕ. TGF-ß is a key factor for M2 polarization of macrophages following IVD injury.

Fate of the intervertebral disc and analysis of its risk factors following high-energy traumatic thoracic and lumbar fractures: MRI results of minimum five years after injury.

OBJECTIVE: Disc degenerative disease is regarded as the primary cause of low back pain. The purpose of this study was to clarify the fate of Intervertebral disc (IVD) following the traumatic event through long-term follow-up and to identify the risk factors for irrevocable degeneration. METHODS: 78 non-operative patients who had traumatic fracture of the thoracic or lumbar at minimum 5 years before were enrolled. Disc degeneration was assessed by modified Pfirrmann grading system. The Acceleration of disc degeneration (ADD) was defined as the difference of grade between IVD adjacent to fractured vertebra and their neighbors with increasing grade from 0 to 7. A novel classification of Endplate injury (EPI) with increasing severity from type I to III was proposed based on the injured morphology. The long-term fate of IVD adjacent to fractured vertebra and risk factors for ADD were analyzed. RESULTS: The mean time of last follow-up was 15.4 ± 10.8 years (range 5-49 years) after injury. 138 (68.66%) IVDs were graded 0 of ADD, 44 (21.89%) were 1-3 and 19 (9.45%) were 4-7. Multivariate binary logistic regression analyses showed that injured posterior ligamentous complex (PLC) and EPI type III were independent risk factors for ADD. CONCLUSIONS: Injured PLC and EPI type III were independent risk factors for ADD in patients with traumatic thoracic or lumbar fracture. For such patients without risk factors for ADD, the non-intervertebral fusion should be given a priority if surgery is necessary.

Retrospective study on the incidence of cats and dogs' spinal injuries by computed tomographic scan. Part I: Cervical and Cervicothoracic / Estudo retrospectivo sobre incidência de injúrias em coluna vertebral de cães e gatos por meio de exame tomográfico. Parte I: Cervical e Cervicotorácica

Injuries involving the spine are frequent in dogs and knowledge of them is important to define the patient's treatment and prognosis. The objective of this retrospective study was to describe the epidemiological profile of animals and lesions in the cervical (C1-5) and cervicothoracic (C6-T2) spine diagnosed through tomographic examination. Compilation of computed tomography (CT) reports for the referred regions was carried out in a diagnostic center between 01/04/2017 and 30/04/2020, with or without contrast, from the clinical routine, in order to relate the most common lesions and their locations, as well as the species, breeds and ages most affected. A total of 1164 CT scans were performed in the period, 57.56% (n=670/1164) for the spine, with 89.7% (n=601/670) reports accessed, where both regions referred to here totaled 26.95% of the studies (n=162/601). Male mixed-breed dogs (MBD) showed the most lesions. For the cervical spine, the most identified lesion was disk extrusion and the site was C3-C4, while the mean age for lesions was 8.09±3.55 years. As for cervicothoracic, disk mineralization was more frequent and the mean age for lesions was 6.96±2.93 years. It was concluded that the spine is the main target of CT scans, that lesions related to the intervertebral disk were the main ones identified, and older MBD animals are the main ones affected.

As lesões envolvendo coluna vertebral são frequentes em animais de companhia, podendo ocorrer à nível vertebral, medula espinal, disco intervertebral, meninges ou raízes nervosas, e o conhecimento das mesmas é importante para definir o tratamento e prognóstico do animal. O objetivo desse estudo retrospectivo foi descrever o perfil epidemiológico dos animais e das lesões em coluna vertebral cervical (C1-5) e cervicotorácica (C6-T2) diagnosticadas por meio de exame tomográfico. Realizou-se a compilação de laudos de tomografias computadorizadas para as referidas regiões realizadas em centro diagnóstico comercial, entre 01/04/2017 a 30/04/2020, contrastadas e não-contrastadas, provenientes da rotina clínica, a fim de relacionar as lesões, raças e locais mais comuns. Foram realizados 1164 exames tomográficos no período avaliado, sendo 57,56% (n=670/1164) para a coluna, com 89,7% dos laudos acessados (n=601/670), sendo que as regiões cervical e cervicotorácica somaram 26,95% dos estudos (n=162/601). Em ambas regiões, os cães sem raça definida (SRD) machos foram os que mais demonstraram lesões. Para a coluna cervical, a lesão mais identificada foi extrusão de disco e o local mais afetado foi C3-C4, enquanto a média de idade para lesões foi 8,09±3,55 anos. Já para cervicotorácica, a mineralização de disco foi mais frequente e média de idade para ocorrência de lesões foi de 6,96±2,93 anos. Concluiu-se que a coluna vertebral foi o principal alvo de tomografias, as lesões relacionadas ao disco intervertebral foram as mais identificadas, sendo animais SRD com idade avançada os mais acometidos.

Retrospective study on the incidence of cats and dogs' spinal injuries by computed tomographic scan. Part II: Thoracolumbar and lumbosacral / Estudo retrospectivo sobre incidência de injúrias em coluna vertebral de cães e gatos por meio de exame tomográfico. Parte II: Toracolombar e Lombossacral

For vertebromedullary injuries, epidemiological knowledge is essential to guide the choice of the most effective diagnostic method. The objective of this retrospective study was to describe the epidemiological profile of animals and thoracolumbar and lumbosacral spine lesions diagnosed by computed tomography scan. A compilation of CT scan reports for the aforementioned regions performed in a comercial diagnostic center from 04/01/2017 to 04/30/2020, contrasted and non-contrasted, from routine, was performed in order to list the most common lesions and their locations, as well as the species, breeds and ages most affected. There were 1164 CT scans performed in the period evaluated, all of them in dogs, 57,56% (n=670) for the spine, with 89,7% reports accessed (n=601), where the regions mentioned here added up to 73,05% studies (n=439). In both regions, male French Bulldog dogs had the most injuries. For the thoracolumbar region, disk mineralization, followed by extrusion, were the most frequent injuries, while the site was T12-13 and the mean age 6,5±3,63 years old. In the lumbosacral, disk protrusion was most frequent, the most affected site was L7-S1 and age 6,65±3,79 years. It was concluded that the spine is the main target of CT scans, and that lesions related to the intervertebral disk were the main ones identified, with chondrodystrophic animals being more predisposed to injury.

Para lesões vertebromedulares é indispensável o conhecimento epidemiológico para direcionar a escolha do método diagnóstico mais eficaz. O objetivo desse estudo retrospectivo foi descrever o perfil epidemiológico dos animais e das lesões em coluna vertebral toracolombar e lombossacral diagnosticadas através de exame tomográfico. Realizou-se a compilação de laudos de tomografias computadorizadas para as referidas regiões realizadas em centro diagnóstico comercial, entre 01/04/2017 a 30/04/2020, contrastadas e não-contrastadas, provenientes da rotina, a fim de relacionar as lesões e seus locais de ocorrência, bem como a espécie, raças e idades mais comuns. Foram realizados 1164 exames tomográficos no período avaliado, sendo 57,56% (n=670) para a coluna, com 89,7% laudos acessados (n=601), nos quais as regiões toracolombar e lombossacral somaram 73,05% dos estudos (n=439). Em ambas as regiões, os cães Bulldog Francês machos foram os que mais apresentaram lesões. Para a região toracolombar, a mineralização de disco, seguida pela extrusão, foram as lesões mais frequentes, enquanto o local foi T12-13 e a média de idade 6,5±3,63 anos. Na lombossacral, a protusão de disco foi mais frequente, o local mais afetado foi L7-S1 e idade de 6,65±3,79 anos. Concluiu-se que a coluna vertebral é o principal alvo de tomografias, e que as lesões relacionadas ao disco intervertebral foram as principais identificadas, sendo os animais condrodistróficos mais predispostos a lesões.

Classification of unilateral cervical locked facet with or without lateral mass-facet fractures and a retrospective observational study of 55 cases.

This study describes a morphology-based unilateral cervical facet interlocking classification in an attempt to clarify the injury mechanism, instability, neurological deficits, radiological features, and determine optimum management strategies for these injuries. A total of 55 patients with unilateral cervical locked facet (UCLF) involving C3 to C7 were identified between January 1, 2012 and December 1, 2019. The injuries were classified into three types, and they were further divided into six subtypes using three-dimensional computed tomography. The injury mechanism, clinical features, neurological deficits, and imaging characteristics were analyzed, and the appropriate treatment strategies for UCLF were discussed. UCLFs were divided into the following six subtypes: UCLF without lateral mass-facet fracture (type I) in nine cases, with superior articular process fracture (type II A) in 22, with inferior articular process fracture (type II B) in seven, both superior and inferior articular process fractures (type II C) in four, with lateral mass splitting fracture (type III A) in three, and with lateral mass comminution fractures (type III B) in ten. A total of 22 (40.0%) of the 55 patients presented with radiculopathy, and 23 patients (41.8%) had spinal cord injuries. The subtype analyses showed high rates of radiculopathy in types II A (68.2%) and II C (75.0%), as well as significant spinal cord injury in types I (77.8%) and III (61.5%). Destruction of the facet capsule was observed in all patients, but the injury of disc, ligamentous complex, and vertebra had a significant difference among the types or subtypes. The instability parameters of the axial rotation angle, segmental kyphosis, and sagittal displacement showed significant differences in various types of UCLF. Closed reduction by preoperative and intraoperative general anesthesia traction was achieved in 27 patients (49.1%), and successful rate of closed reduction in type I (22.2%) was significantly lower than that in type II (51.5%) and type III (61.5%). A total of 35 of 55 patients underwent a single anterior fixation and fusion, 10 patients were treated with posterior pedicle and (or) lateral mass fixation, and combined surgery was performed in ten patients. Ten patients (18.2%) with a poor outcome were observed after first surgery. Among them, 3 patients treated with a single anterior surgery had persistent or aggravated radiculopathy and posterior approach surgery with ipsilateral facet resection, foramen enlargement, and pedicle and (or) lateral mass screw fixation was performed immediately, 5 patients treated with a short-segment posterior surgery showed mild late kyphosis deformity, and 2 patients with vertebral malalignment were encountered after anterior single-level fusion during the follow-up. This retrospective study indicated that UCLF is a rotationally unstable cervical spine injury. The classification proposed in this study will contribute to understanding the injury mechanism, radiological characteristics, and neurological deficits in various types of UCLF, which will help the surgeons to evaluate the preoperative closed reduction and guide the selection of surgical approach and fusion segment.

An Injectable Hyaluronic Acid Hydrogel Promotes Intervertebral Disc Repair in a Rabbit Model.

STUDY DESIGN: An in vivo model to study the effect of an injectable hyaluronic acid (HA) hydrogel following puncture-induced lumbar disc injury in rabbits. OBJECTIVES: The aim of this study was to determine the efficacy of an injectable HA hydrogel to maintain disc height and tissue hydration, promote structural repair, and attenuate inflammation and innervation in the lumbar discs. SUMMARY OF BACKGROUND DATA: Previously, we have demonstrated that HA hydrogel alleviated inflammation, innervation, and pain to promote disc repair. Nevertheless, the effect of an injectable HA hydrogel in the lumbar disc in a weight-bearing animal model was not performed. METHODS: We have adopted a surgically puncture-induced disc injury at lumbar levels in a rabbit model. The discs were grouped into sham, puncture with water injection, and puncture with HA hydrogel injection. Postoperatively, we measured changes in disc height using x-ray. We used magnetic resonance imaging to assess disc degeneration on tissue hydration after euthanasia. Post-mortem, we determined histological changes, innervation (PGP9.5) and inflammation (interleukin [IL]-6, IL-1ß, and tumor necrosis factor [TNF]-α) in the discs. RESULTS: We have demonstrated a significant reduction of disc height and T2/T1ρ mapping with histological evidence of degenerative discs, increase of innervation and inflammation in puncture-induced disc injury over time. In the HA hydrogel group, disc height was increased at weeks four and eight. A slight increase of T2 mapping, but significantly in T1ρ mapping, was observed in the HA hydrogel group at week 8. We observed homogenous NP distribution and organised AF lamellae at week eight and a slight reduced innervation score in the treatment group. HA hydrogel significantly downregulated IL-6 expression at day 1. This, however, was only slightly reduced for IL-1ß and TNF-α. CONCLUSION: An injectable HA hydrogel had the protective effects in suppressing the loss of disc height, promoting tissue hydration for structural repair, and attenuating inflammation and innervation to prevent further disc degeneration.Level of Evidence: N/A.

The Application of Mesenchymal Stromal Cells and Their Homing Capabilities to Regenerate the Intervertebral Disc.

Chronic low back pain (LBP) remains a challenging condition to treat, and especially to cure. If conservative treatment approaches fail, the current "gold standard" for intervertebral disc degeneration (IDD)-provoked back pain is spinal fusion. However, due to its invasive and destructive nature, the focus of orthopedic research related to the intervertebral disc (IVD) has shifted more towards cell-based therapeutic approaches. They aim to reduce or even reverse the degenerative cascade by mimicking the human body's physiological healing system. The implementation of progenitor and/or stem cells and, in particular, the delivery of mesenchymal stromal cells (MSCs) has revealed significant potential to cure the degenerated/injured IVD. Over the past decade, many research groups have invested efforts to find ways to utilize these cells as efficiently and sustainably as possible. This narrative literature review presents a summary of achievements made with the application of MSCs for the regeneration of the IVD in recent years, including their preclinical and clinical applications. Moreover, this review presents state-of-the-art strategies on how the homing capabilities of MSCs can be utilized to repair damaged or degenerated IVDs, as well as their current limitations and future perspectives.

The Role of Panx3 in Age-Associated and Injury-Induced Intervertebral Disc Degeneration.

Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for Panx3 expression in the intervertebral disc (IVD), its function in this cartilaginous joint structure remained unknown. Using Panx3 knockout mice, this study investigated the role of Panx3 in age-associated IVD degeneration and degeneration induced by annulus fibrosus (AF) needle puncture. Loss of Panx3 did not significantly impact the progression of age-associated histopathological IVD degeneration; however, loss of Panx3 was associated with decreased gene expression of Acan, Col1a1, Mmp13 and Runx2 and altered localization of COLX in the IVD at 19 months-of-age. Following IVD injury in the caudal spine, histological analysis of wild-type mice revealed clusters of hypertrophic cells in the AF associated with increased pericellular proteoglycan accumulation, disruptions in lamellar organization and increased lamellar thickness. In Panx3 knockout mice, hypertrophic AF cells were rarely detected and AF structure was largely preserved post-injury. Interestingly, uninjured IVDs adjacent to the site of injury more frequently showed evidence of early nucleus pulposus degeneration in Panx3 knockout mice but remained healthy in wild-type mice. These findings suggest a role for Panx3 in mediating the adaptive cellular responses to altered mechanical stress in the IVD, which may buffer aberrant loads transferred to adjacent motion segments.

Risk of intervertebral disc joint puncture during lumbar puncture.

OBJECTIVE: Penetration of intervertebral disc joint during lumbar puncture might be unnoticed during procedure. However, accelerated degeneration of the disc joint is a long-term consequence of inadvertent penetration. In this paper, we aimed to demonstrate and evaluate the risk of disc puncture during standard lumbar puncture. PATIENTS AND METHODS: 50 human cadavers were used in this study. Disc puncture risk was assessed by using worst case scenario model. Lumbar puncture was performed in a standard fashion using midline route at L3-4, L4-5 and L5-S1 levels. The needle was advanced until it hit resistance from the bone. Lateral X-ray was used to visualize the needle position. Needle ended up in two possible locations - posterior vertebral body wall and intervertebral disc space. RESULTS: The probability of puncturing the joint was 20 % for L3-4, 38 % for L4-5, 16 % for L5-S1. Total probability of disc penetration was 25 %. Statistical analysis revealed significantly increased risk for performing LP at L4-5 level in comparison with L5-S1 (p = 0.023). CONCLUSION: Lumbar puncture carries significant risk of intervertebral disc penetration. This complication is not realized during the procedure and lead to accelerated joint degeneration.

Percutaneous intervertebral bridging cementoplasty for adjacent multilevel osteoporotic thoracolumbar fractures with vertebral endplate-disc complex injury: technical note.

This paper describes a minimally invasive technique of percutaneous intervertebral bridging cementoplasty (PIBC) to augment the fractured vertebrae and immobilize the intervertebral space with endplate-disc complex injury simultaneously. Thirty-two patients with adjacent multilevel osteoporotic thoracolumbar fractures (AMOTLFs) and vertebral endplate-disc complex injury (EDCI) treated by PIBC were retrospectively reviewed. The PIBC technique was a combination of puncture, balloon expansion and bridging cementoplasty. The clinical and radiological assessments were reviewed. The operation time was 82.8 ± 32.5 min, and blood loss was 76.9 ± 31.7 mL. A cement bridge was connected between the two fractured vertebrae across the injured intervertebral space. VAS at three time points including pre-operation, post-operation 1 day and final follow-up was 6.9 ± 0.9, 2.9 ± 0.8 and 1.7 ± 0.8, respectively; ODI at three time points was (71.1 ± 7.8)%, (18.4 ± 5.7)%, and (10.3 ± 5.7)%, respectively; Cobb angle at three time points was 46.0° ± 10.4°, 25.9° ± 8.5°, and 27.5° ± 7.1°, respectively. Compared with pre-operation, VAS, ODI and Cobb angle were significantly improved at post-operation 1 day and final follow-up (P < 0.05). Clinical asymptomatic cement leakage was observed in thirteen patients. No vessel or neurological injury was observed. PIBC may be an alternative way of treatment for AMOTLFs with EDCI. The technique is a minimally invasive surgery to augment the fractured vertebrae and immobilize the injured intervertebral space simultaneously.

Rapid increase in intradiscal pressure in porcine cervical spine units negatively impacts annulus fibrosus strength.

Vertebral endplate fracture is generally accepted to occur as a result of excessive, typically rapid, pressure developed within the intervertebral disc. Clinical evidence of disc disorders later in life following endplate fracture suggests that the disc is also impacted by the fracture event. There is an abundance of evidence to indicate that loss of disc pressure at the time of fracture alters annulus fibrosus loading which could impact disc health long-term. However, little is known regarding the isolated impact of the rapid disc pressurization during the fracture event. This study sought to determine if rapid disc pressurization impacts mechanical properties of the annulus. Intervertebral discs of porcine cervical functional spine units (FSU) were pressurized via rapid injection of hydraulic fluid (standard motor oil). FSUs were subsequently grouped according to whether the pressurization resulted in endplate fracture ('fracture'; n = 9) or not ('non-fracture'; n = 13). Annular tensile properties and lamellar adhesion strength were quantified for both fractured and non-fractured samples. A third group was also examined in which FSUs did not undergo the pressurization protocol ('control'; n = 10). Annular tensile properties were not found to be statistically different between the three conditions (p > 0.05). Lamellar adhesion strength, in contrast, was found to be, on average, 53% lower in specimens which were pressurized compared to control, non-pressurized samples (p = 0.03). Further, no statistical differences in adhesion strength was found between fractured and non-fractured pressurized samples (p = 0.990) indicating that rapid pressurization , and not the presence of an endplate fracture, impacted the mechanical properties of the annulus. Decreased lamellar adhesion strength increases the potential of delamination, which can lead to disc disorders.

Contribution of injured posterior ligamentous complex and intervertebral disc on post-traumatic instability at the cervical spine.

Posterior ligamentous complex (PLC) and intervertebral disc (IVD) injuries are common cervical spine flexion-distraction injuries, but the residual stability following their disruption is misknown. The objective of this study was to evaluate the effect of PLC and IVD disruption on post-traumatic cervical spine stability under low flexion moment (2 Nm) using a finite element (FE) model of C2-T1. The PLC was removed first and a progressive disc rupture (one third, two thirds and complete rupture) was modeled to simulate IVD disruption at C2-C3, C4-C5 and C6-C7. At each step, a non-traumatic flexion moment was applied and the change in stability was evaluated. PLC removal had little impact at C2-C3 but increased local range of motion (ROM) at the injured level by 77.2% and 190.7% at C4-C5 and C6-C7, respectively. Complete IVD rupture had the largest impact on C2-C3, increasing C2-C3 ROM by 181% and creating a large antero-posterior displacement of the C2-C3 segment. The FE analysis showed PLC and disc injuries create spinal instability. However, the PLC played a bigger role in the stability of the middle and lower cervical spine while the IVD was more important at the upper cervical spine. Stabilization appears important when managing patients with soft tissue injuries.

Treatment of Intervertebral Disc Degeneration in Wistar Rats with Mesenchymal Stem Cells.

We studied the effect of erythropoietin on functional properties of mesenchymal stem cells under conditions of oxidative stress and their therapeutic potential in the treatment of intervertebral disc degeneration in Wistar rats. It was shown that erythropoietin stimulates proliferation under conditions of oxidative stress. Injection of bone marrow mesenchymal stem cells into the damaged intervertebral disc was followed by an increase in the height of the intervertebral disc and activation of repair processes in the nucleus pulposus. The combination of mesenchymal stem cells with erythropoietin provides the best effect of cell therapy in case of intervertebral disc damage.

Influence of Genetic Background and Sex on Gene Expression in the Mouse (Mus musculus) Tail in a Model of Intervertebral Disc Injury.

To facilitate rational experimental design and fulfill the NIH requirement of including sex as a biologic variable, we examined the influences of genetic background and sex on responses to intervertebral disc (IVD) injury in the mouse tail. The goal of this study was to compare gene expression and histologic changes in response to a tail IVD injury (needle puncture) in male and female mice on the DBA and C57BL/6 (B6) backgrounds. We hypothesized that extracellular matrix gene expression in response to IVD injury differs between mice of different genetic backgrounds and sex. Consistent changes were detected in gene expression and histologic features after IVD injury in mice on both genetic backgrounds and sexes. In particular, expression of col1a1 and adam8 was higher in the injured IVD of DBA mice than B6 mice. Conversely, col2a1 expression was higher in B6 mice than DBA mice. Sex-associated differences were significant only in B6 mice, in which col2a1 expression was greater in male mice than in female. Histologic differences in response to injury were not apparent between DBA and B6 mice or between males and females. In conclusion, mouse tail IVD showed sex- and strain-related changes in gene expression and histology after needle puncture. The magnitude of change in gene expression differed with regard to genetic background and, to a lesser degree, sex.

Long-term histological analysis of innervation and macrophage infiltration in a mouse model of intervertebral disc injury-induced low back pain.

Low back pain (LBP) is a leading cause of global disability. Multiple anatomical, cellular, and molecular factors are implicated in LBP, including the degeneration of lumbar intervertebral discs (IVDs). We previously described a mouse model that displays behavioral symptoms of chronic LBP. Here, we investigated the development of pathological innervation and macrophage infiltration into injured IVDs following a puncture injury in mice over 12 months. 2-month old CD1 female mice underwent a single puncture of the ventral L4/5 IVD using a 30G needle, and were sacrificed 4 days and 0.5-, 3-, 6- and 12-months post-injury. Severity of disc degeneration was assessed using colorimetric staining. IVD innervation was measured by PGP9.5-immunoreactivity (-ir) and calcitonin gene-related peptide-ir (CGRP-ir). Macrophage accumulation into IVDs was detected by F4/80-ir. Mechanical IVD injury resulted in severe degeneration and increased PGP9.5-ir nerve fiber density starting at 4 days that persisted for up to 12 months and dorsal herniations began to occur at 3 months. CGRP-ir was also upregulated in injured IVDs, with the largest increase at 12 months after injury. Infiltration of F4/80-ir macrophages was observed in injured IVDs by day 4 both dorsally and ventrally, with the latter diminishing in the later stage. Persistent LBP is a complex disease with multiple underlying pathologies. By highlighting pathological changes in IVD innervation and inflammation, our study suggests that strategies targeting these mechanisms might be useful therapeutically.