Significance of Oxidative Stress in the Diagnosis and Subtype Classification of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a common illness of aging, and its pathophysiological process is mainly manifested by cell aging and apoptosis, an imbalance in the production and catabolism of extracellular matrix, and an inflammatory response. Oxidative stress (OS) is an imbalance that decreases the body's intrinsic antioxidant defense system and/or raises the formation of reactive oxygen species and performs multiple biological functions in the body. However, our current knowledge of the effect of OS on the progression and treatment of IVDD is still extremely limited. In this study, we obtained 35 DEGs by differential expression analysis of 437 OS-related genes (OSRGs) between IVDD patients and healthy individuals from GSE124272 and GSE150408. Then, we identified six hub OSRGs (ATP7A, MELK, NCF1, NOX1, RHOB, and SP1) from 35 DEGs, and the high accuracy of these hub genes was confirmed by constructing ROC curves. In addition, to forecast the risk of IVDD patients, we developed a nomogram. We obtained two OSRG clusters (clusters A and B) by consensus clustering based on the six hub genes. Then, 3147 DEGs were obtained by differential expression analysis in the two clusters, and all samples were further divided into two gene clusters (A and B). We investigated differences in immune cell infiltration levels between different clusters and found that most immune cells had higher infiltration levels in OSRG cluster B or gene cluster B. In conclusion, OS is important in the formation and progression of IVDD, and we believe that our work will help guide future research on OS in IVDD.

The role of the greater trochanter pain syndrome in lumbar degenerative disc disease surgery.

PURPOSE: Greater trochanter pain syndrome (GTPS) is highly discussed during spine surgeons, accompanies lumbar pain and complicates differential diagnosis. The aim is to raise awareness among physicians and demonstrate the lumbar spine degenerative diseases (LSDD) association with GTPS. METHODS: A retro-prospective analysis enrolled 172 patients with LSDD with GTPS signs. Group I - retrospective (n = 112), group II - prospective (n = 60). Patients of group II with the confirmed diagnosis clinically and by the ultrasound recieved a GCS injection (Betamethasone 2 mg\ml + 5 mg\ml - 1.0). Also the VAS, X-ray and SPSS Statistics package were used. RESULTS: 112 patients in group I, 89 (79.5%) had increased pain in the hip early postOp to 7.8 points by VAS. All patients required trigger point injections of GCS and 68 (77%) received a repeat injection. 76 from 112 patients were tracked for long-term results, and recurrence of GTPS was detected in five people who treated conservatively for three months without dynamics. They were identified GTPS by ultrasound. During the injection, 39 from 43 (90%) patients noted pain reduction to 2.1 by VAS, but symptoms of radiculopathy or spinal stenosis persisted. Two patients (5%) did not note any changes. Two patients (5%) noted complete pain regression and refused the surgery. CONCLUSION: Timely detection of GTPS among spinal surgeons influences tactics and, in some cases, allows one to avoid unnecessary surgical interventions. In turn, ignoring the symptoms of GTPS in the preoperative period can lead to pain intensification in the greater trochanter after surgery for degenerative diseases of the spine.

Oblique Lateral Interbody Fusion with Anterolateral Screw Fixation Is as Effective as with Posterior Percutaneous Pedicle Screw Fixation in Treating Single-Segment Mild Degenerative Lumbar Diseases.

BACKGROUND Oblique lateral interbody fusion (OLIF) is a new and minimally invasive surgery. This study aimed to compare the clinical efficacy and safety of oblique lateral interbody fusion with anterolateral screw fixation and with posterior percutaneous screw fixation in treating single-segment mild degenerative lumbar diseases. MATERIAL AND METHODS A retrospective analysis was performed on 51 patients with single-segment mild degenerative lumbar diseases who received OLIF from April 2017 to January 2020 in Hong Hui Hospital, Xi'an Jiao Tong University; 24 and 27 patients received OLIF with anterolateral screw fixation (OLIF+AF) and OLIF with posterior percutaneous screw fixation (OLIF+PF), respectively. Anesthesia time, operation time, intraoperative blood loss, intraoperative fluoroscopy number, hospital stay, postoperative complications, Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) score, anterior and posterior disc heights, foraminal height, and fusion rate of the 2 groups were compared to assess clinical and radiological outcomes. RESULTS Anesthesia time, operation time, intraoperative blood loss, number of intraoperative fluoroscopy, and VAS score in the OLIF+AF group were significantly better than those in the OLIF+PF group (P<0.05). There were no significant differences in ODI score, anterior and posterior disc heights, foraminal height, fusion rate, and incidence of complications between the 2 groups (P<0.05). CONCLUSIONS OLIF+AF in treating single-segment mild degenerative lumbar diseases produces a satisfactory clinical effect. Moreover, OLIF+AF does not invade the paraspinal muscle group, thereby reducing trauma, postoperative residual low back pain, operation time, bleeding, and frequency of fluoroscopy. Thus, OLIF+AF is a feasible treatment method for single-segment mild degenerative lumbar diseases.

Is intervertebral disc degeneration associated with reduction in serum ferritin?

OBJECTIVE: Ferritin autophagy is characterized by intracellular ferroptosis and selective ferritin degradation. However, the role of ferritin in the development of intervertebral disc degeneration (IDD) has not been elucidated. The study aimed to investigate the role of serum iron metabolism markers, especially serum ferritin (SF), in IDD. METHODS: 217 patients who came to the spine surgery department of our hospital for low back pain were recruited, and blood samples were collected for routine examination after admission. The cumulative grade was also calculated by summing up the Pfirrmann grade of all lumbar discs. RESULTS: Correlation analysis showed that cumulative grade was correlated with SF (r = - 0.185, p = 0.006), not with serum iron (SI), transferrin saturation (TS), unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC) (all p > 0.05). In addition, SF levels in the low severity IDD were significantly higher than high severity IDD in cumulative grade (p = 0.003) and single disc grade. No statistically significant difference was found in the other four indicators. A statistically significant difference was observed between the high (cumulative grade > 17) and low score (cumulative grade ≤ 17) groups in terms of age. According to the ROC curve, the cut-off value of SF levels was 170.5. Patients with SF < 170.5 ng/mL had severe disc degeneration. The sensitivity and specificity were 0.635 and 0.602, respectively. CONCLUSION: This study preliminarily showed that SF was negatively correlated with the degree of IDD and can be used to predict IDD severity.

[A validated new classification for intervertebral disk degeneration]. / Novaya validizirovannaya klassifikatsiya klassov degeneratsii mezhpozvonkovykh diskov.

OBJECTIVE: To develop a new validated classification of intervertebral disc degeneration. MATERIAL AND METHODS: A retrospective observational single-center study included medical records of patients with and without degenerative disease of lumbar intervertebral discs. The interval values of apparent diffusion coefficient (ADC) of intervertebral discs were grouped into degeneration classes. RESULTS: The study included medical records of 100 patients. A quantitative analysis of data showed that mean ADC has a significant correlation with severity of lumbosacral disc degeneration according to classification by Pfirrmann et al. Lumbar intervertebral discs with degeneration grade 3-4 were less homogeneous compared to grade 2-3. Among discs with degeneration grade 4, mean ADC was significantly higher in case of hernia (p=0.01). Conversely, mean ADC was significantly higher in the absence of hernia for discs grade 3 (p=0.04). Combination of all data is presented as original classification of lumbosacral disc degeneration based on mean ADC. CONCLUSION: The developed classification can be recommended for radiologists, neurologists and neurosurgeons.

Roles of miR-182 in Intervertebral Disc Degeneration and its Potential Prognostic Value.

BACKGROUND: MicroRNAs were reported to be involved in the progression of intervertebral disc degeneration (IDD). This study focused on the potential prognostic value and the underlying mechanism of miR-182 in IDD. METHODS: The expression level of miR-182 in plasma samples from 60 IDD patients and 60 healthy controls were examined in the present study. Then, the relationship between miR-182 expression and clinical features of IDD patients was analyzed. Moreover, the nucleus pulposus (NP) cells were cultured and transfected with either miR-182 inhibitor, mimics, or NC to explore the effects of miR-182 on cell proliferation and apoptosis. Furthermore, expression levels of proliferation and apoptosis-related proteins Bcl-2, Bax, and Caspase-3 were also evaluated. RESULTS: The expression level of miR-182 was dramatically increased in plasma samples of IDD patients compared with the controls. Moreover, ROC analysis indicated that miR-182 was a feasible diagnostic indicator for the diagnosis of IDD. According to the Japanese Orthopaedic Association (JOA) score, the prognosis of patients with the lower expression levels of miR-182 was better than for those with the higher expression levels of miR-182 in IDD. Furthermore, the miR-182 inhibitor significantly increased the proliferation, decreased the apoptosis of human NP cells, and altered the expression of proliferation and apoptosis-related proteins Bcl-2, Bax, and Caspase-3. On the contrary, miR-182 mimics notably inhibited proliferation but promoted apoptosis of human NP cells and increased Bax and Caspase-3 expressions while reducing the Bcl-2 level. CONCLUSIONS: miR-182 was negatively correlated with the prognosis of the IDD patients and affected the proliferation and apoptosis of NP cells in vitro.

Association between excessive smartphone use and cervical disc degeneration in young patients suffering from chronic neck pain.

BACKGROUND: With the popularity of smartphones, cervical spondylosis is becoming more and more common among young people. The aim of this study was to investigate the association between excessive smartphone use and cervical disc degeneration in young patients suffering from chronic neck pain. METHODS: A total of 2438 young patients suffering from chronic neck pain were included into this study. All patients underwent the Magnetic Resonance Imaging (MRI) examination of the cervical spine. The degree of cervical disc degeneration, the dependent variable, was evaluated by Cervical Disc Degeneration Scale (CDDS) which was developed from Pfirrmann classification. Smartphone use, the primary independent variable, was assessed by Smartphone Addiction Scale (SAS). RESULTS: In all, 52.9% patients were categorized as smartphone overuse. Patients with overuse of smartphones had higher CDDS scores than those who did not use smartphone excessively. CONCLUSIONS: The results indicate that cervical disc degeneration may be associated with excessive smartphone use, such use may lead to cervical spondylosis.

Differentiation between infectious spondylodiscitis versus inflammatory or degenerative spinal changes: How can magnetic resonance imaging help the clinician?

Spondylodiscitis is a complex disease whose diagnosis and management are still challenging. The differentiation between infectious and non-infectious aetiology is mandatory to avoid delays in the treatment of life-threatening infectious conditions. Imaging methods, in particular magnetic resonance imaging (MRI), play a key role in differential diagnosis. MRI provides detailed anatomical information, especially regarding the epidural space and spinal cord, and may allow differential diagnosis by assessing the characteristics of certain infectious and inflammatory/degenerative lesions. In this article, we provide an overview of the radiological characteristics and differentiating features of non-infectious inflammatory spinal disorders and infectious spondylodiscitis, focussing on MRI results and presenting relevant clinical and pathological features that help early diagnosis.

[Intervertebral disc-related occupational diseases of the lumbar and cervical spines]. / Bandscheibenbedingte Berufskrankheiten der Lenden- und Halswirbelsäule.

Intervertebral disc-related diseases of the cervical and lumbar spine are considered to be occupational diseases, if the occupational and medical prerequisites are fulfilled and the causal connection between the prerequisites is likely. The working conditions include occupational burdens with long-term lifting and carrying of heavy loads or long-term activities in an extremely bent position of the torso, long-term carrying of heavy loads on the shoulders and long-term effects of whole-body vibration in a sitting position. A medical prerequisite is fulfilled by a damage pattern with chronic lower back or neck pain and damage of the cervical or lumbar vertebrae in a conform manner.In the legal assessment the occupational conditions are examined by the preventive services of the statutory accident insurance and the medical conditions by the medical expert. Furthermore, the medical expert examines the causal connection between the fulfilled prerequisites, whereby the temporal connection (reaching the minimum load dose before realization of the conform damage pattern) and by exclusion of other competing factors are essential. As of 1 January 2021 the necessity to quit the burdening occupation has been omitted by law.

Challenges in the clinical diagnosis of psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic heterogeneous inflammatory musculoskeletal disease. The non-specific and often subtle manifestations make early diagnosis and subsequent treatment challenging. In the absence of diagnostic criteria and biomarkers, the diagnosis is often delayed leading to poor long-term outcomes. In addition, the differential diagnosis of a patient presenting with arthritis in the setting of skin psoriasis is wide due to symptom overlap with many other diseases. Peripheral arthritis, dactylitis, enthesitis and axial arthritis are the 4 domains of musculoskeletal involvement in PsA and careful examination of each domain by a rheumatologist is the first step for a correct diagnosis. Other extra-musculoskeletal features such as the presence of uveitis, inflammatory bowel disease, nail psoriasis and elevated acute phase reactants aid in the diagnosis of PsA. Screening patients with skin psoriasis using validated questionnaires might help in early diagnosis especially when coupled with imaging.

Degenerative lumbar scoliosis: added value of coronal images to routine lumbar MRI for nerve root compromise.

OBJECTIVES: Radiating pain in degenerative scoliosis is primary indication for surgery. However, axial and sagittal MR images are limited for identifying nerve root compromise. Therefore, we aimed to assess the value of coronal images for evaluating nerve root compromise in degenerative scoliosis. METHODS: Forty-six patients (mean 70 years; range 41-91 years; 8 men) with degenerative scoliosis were enrolled. Coronal images were added to routine MRI. Two radiologists independently reviewed 350 nerve roots in two MRI sets: sagittal images alone (set 1) and coronal and sagittal images combined (set 2). The following features were evaluated: interpedicular height, lateral osteophyte, asymmetric bulging disc, lateral listhesis, anterolisthesis, axial rotation angle, facet arthrosis, ligamentum flavum thickening, and pseudoarticulation. Symptomatic levels were determined by transforaminal selective nerve root block. RESULTS: There were 80 symptomatic and 270 asymptomatic nerve roots. The sensitivity (86%) and accuracy (93%) of set 2 were significantly higher than set 1 (53% and 87%) for radiculopathy, while specificity was similar between two sets (set 1, 97%; set 2, 95%). The AUC was significantly different between two sets (set 1, 0.853; set 2, 0.942). The negative interpedicular height difference, longer lateral osteophyte, asymmetric bulging disc, lateral listhesis, negative axial rotation angle difference, and pseudoarticulation were associated with change of grades between set 1 and set 2. CONCLUSION: Coronal images are helpful for diagnosing nerve root compromise in patients with degenerative scoliosis. KEY POINTS: • Sagittal and axial images have low sensitivity for detection of extraforaminal nerve root compromise in degenerative scoliosis. • Addition of coronal images may improve the sensitivity in nerve root compromise. • The structural changes that may contribute to nerve root compromise can also be easily assessed with coronal images.

Genome-wide meta-analysis identifies genetic locus on chromosome 9 associated with Modic changes.

BACKGROUND: Low back pain (LBP) is a common disabling condition. Lumbar disc degeneration (LDD) may be a contributing factor for LBP. Modic change (MC), a distinct phenotype of LDD, is presented as a pathological bone marrow signal change adjacent to vertebral endplate on MRI. It is strongly associated with LBP and has heritability around 30%. Our objective was to identify genetic loci associated with MC using a genome-wide meta-analysis. METHODS: Presence of MC was evaluated in lumbar MRI in the Northern Finland Birth Cohort 1966 (n=1182) and TwinsUK (n=647). Genome-wide association analyses were carried out using linear regression model. Inverse-variance weighting approach was used in the meta-analysis. RESULTS: A locus associated with MC (p<5e-8) was found on chromosome 9 with the lead SNP rs1934268 in an intron of the PTPRD gene. It is located in the binding region of BCL11A, SPI1 and PBX3 transcription factors. The SNP was nominally associated with LBP in TwinsUK (p=0.001) but not associated in the UK Biobank (p=0.914). Suggestive signals (p<1e-5) were identified near XKR4, SCIN, MGMT, DLG2, ZNF184 and OPRK1. CONCLUSION: PTPRD is a novel candidate gene for MC that may act via the development of cartilage or nervous system; further work is needed to define the mechanisms underlying the pathways leading to development of MC. This is the first genome-wide meta-analysis of MC, and the results pave the way for further studies on the genetic factors underlying the various features of spine degeneration and LBP.

Intervertebral disc degeneration in mice with type II diabetes induced by leptin receptor deficiency.

BACKGROUND: The leptin receptor-deficient knockout (db/db) mouse is a well-established model for studying type II diabetes mellitus (T2DM). T2DM is an important risk factor of intervertebral disc degeneration (IVDD). Although the relationship between type I diabetes and IVDD has been reported by many studies, few studies have reported the effects of T2DM on IVDD in db/db mice model. METHODS: Mice were separated into 3 groups: wild-type (WT), db/db, and IGF-1 groups (leptin receptor-deficient mice were treated with insulin-like growth factor-1 (IGF-1). To observe the effects of T2DM and glucose-lowering treatment on IVDD, IGF-1 injection was used. The IVD phenotype was detected by H&E and safranin O fast green staining among db/db, WT and IGF-1 mice. The levels of blood glucose and weight in mice were also recorded. The changes in the mass of the trabecular bone in the fifth lumbar vertebra were documented by micro-computed tomography (micro-CT). Tunnel assays were used to detect cell apoptosis in each group. RESULTS: The weight of the mice were 27.68 ± 1.6 g in WT group, which was less than 57.56 ± 4.8 g in db/db group, and 52.17 ± 3.7 g in IGF-1 injected group (P < 0.05). The blood glucose levels were also significantly higher in the db/db mice group. T2DM caused by leptin receptor knockout showed an association with significantly decreased vertebral bone mass and increased IVDD when compared to WT mice. The db/db mice induced by leptin deletion showed a higher percentage of MMP3 expression as well as cell apoptosis in IVDD mice than WT mice (P < 0.05), while IGF-1 treatment reversed this situation (P < 0.05). CONCLUSIONS: T2DM induced by leptin receptor knockout led to IVDD by increasing the levels of MMP3 and promoting cell apoptosis. IGF-1 treatment partially rescue the phenotype of IVDD induced by leptin receptor knockout.

Objective evaluation of postoperative changes in real-life activity levels in the postoperative course of lumbar spinal surgery using wearable trackers.

BACKGROUND: Lumbar spinal disease causes disabilities in performing daily activities. Operative treatments are aimed at pain relief and rapid return to routine activity. Patient-based outcome measures are used to evaluate pathologies and therapeutic effects associated with lumbar spinal disease. Nevertheless, it remains unknown as to how much such treatment improves activity levels. The purpose of the current study was to measure changes in activity levels before and after lumbar spinal surgery using a wearable activity tracker and to analyze the differences between results and patient-based outcomes. METHODS: Sixty patients who underwent lumbar surgery were studied. The physical activity of participants was objectively evaluated using a wearable Micro-Motion logger system (Actigraph). We measured the amount of activity before and at 1, 3, 6, and 12 months after the surgery to evaluate postoperative changes. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, Roland-Morris Disability Questionnaire and visual analog scale were used to assess patient-based outcomes of pain and activities of daily living-related scores; we analyzed the relationships between scores and actual activity levels. RESULTS: The amount of actual activity decreased significantly 1 month after the surgery compared to that during the preoperative period, which then improved after 3 months postoperatively (p < 0.01). Furthermore, there was a significant improvement 6 months after the surgery compared to that during the preoperative period (p < 0.05). The changes in activity for each period were strongly correlated, regardless of the period. In contrast, a significant improvement was observed at 1 month after the surgery in almost all items of the patient-based questionnaires (p < 0.05). CONCLUSIONS: The objective activity tracker demonstrated that lumbar surgery results in the amount of activity decreasing 1 month just after surgery followed by gradual postoperative recovery within 3 months. By contrast, patient-based outcomes showed improvement in 1 month that was significantly different from the change in actual activity, indicating a gap between patient-oriented clinical scores and their actual activities.

Intervertebral Disc Diseases PART 2: A Review of the Current Diagnostic and Treatment Strategies for Intervertebral Disc Disease.

With an aging population, there is a proportional increase in the prevalence of intervertebral disc diseases. Intervertebral disc diseases are the leading cause of lower back pain and disability. With a high prevalence of asymptomatic intervertebral disc diseases, there is a need for accurate diagnosis, which is key to management. A thorough understanding of the pathophysiology and clinical manifestation aids in understanding the natural history of these conditions. Recent developments in radiological and biomarker investigations have potential to provide noninvasive alternatives to the gold standard, invasive discogram. There is a large volume of literature on the management of intervertebral disc diseases, which we categorized into five headings: (a) Relief of pain by conservative management, (b) restorative treatment by molecular therapy, (c) reconstructive treatment by percutaneous intervertebral disc techniques, (d) relieving compression and replacement surgery, and (e) rigid fusion surgery. This review article aims to provide an overview on various current diagnostic and treatment options and discuss the interplay between each arms of these scientific and treatment advancements, hence providing an outlook of their potential future developments and collaborations in the management of intervertebral disc diseases.

Clinical efficacy of targeted injection of drugs in combination with ozone in treatment of lumbar disc protrusion.

To investigate the clinical efficacy of targeted injection of drugs surrounding the protruded lumbar disc in combination with the ozone in treatment of lumbar disc protrusion. Between January 2017 and January 2019, a total of 120 patients with lumbar disc protrusion were recruited in this study and divided into the control group and observation group, with 60 patients in each group. Patients in the control group received the ozone treatment, while those in the observation group additionally took the targeted injection of betamethasone surrounding the protruded lumbar disc. Following one month of treatment, we compared the short-term efficacy, joint range of motion in bending forward or backward of the lumbar disc, limb function, life quality and functional disturbance before and after treatment. In the observation group, the short-term effectiveness rate was higher than that in the control group (P<0.05), while after treatment, the joint range of motion in bending forward or backward of lumbar disc in the observation group was improved when comparing to the control group (P<0.05). After treatment, BI and Fugl-Meyer scale were all higher in the observation than those in the control group (P<0.05), with a lower Oswestry score (P<0.05). Targeted injection of betamethasone surrounding the protruded lumbar disc in combination with the ozone performs well in short-term efficacy, conducive to the improvement of the lumbar disc function and limb function and alleviation in function disturbance. Thus, this strategy is worthy of being promoted in clinical practice.

Serum miRNAs are potential biomarkers for the detection of disc degeneration, among which miR-26a-5p suppresses Smad1 to regulate disc homeostasis.

Disc degeneration is a common clinical condition in which damaged discs cause chronic pain; however, a laboratory diagnosis method for its detection is not available. As circulating miRNAs have potential as biomarkers, their application in disc degeneration has not been explored. Here, we prepared serum miRNAs from a mouse disc degeneration model and performed miRNA-Seq and quantitative PCR to characterize disc degeneration-associated miRNAs. We identified three miRNAs, including miR-26a-5p, miR-122-5p and miR-215-5p, undergoing perturbation during the pathogenesis of disc degeneration. Specifically, the levels of miR-26a-5p in the serum demonstrated steady increases in the model of disc degeneration, compared with those in the pre-injury samples of younger age or compared with normal controls of the same age but without disc degeneration, whereas the miRNAs miR-122-5p and miR-215-5p exhibited lower expression in post-injury samples than in their counterparts without the surgery. Moreover, we found that miR-26a-5p targets Smad1 expression, and Smad1 negatively regulates Vegfa expression in disc cells, and thus, miR-26a-5p promotes disc degeneration. In summary, we established a method that consistently profiles circulating miRNAs and identified multiple miRNAs as promising biomarkers for disc degeneration, among which miR-26a-5p enhances VEGF expression during disc degeneration through targeting Smad1 signalling.

Pediatric Idiopathic Intervertebral Disc Calcification: Single-Center Series and Review of the Literature.

OBJECTIVE: To review pediatric idiopathic intervertebral disc calcification (PIIVDC) within a single center and within the literature to outline the disease course, management, and outcome. STUDY DESIGN: A retrospective chart review was performed spanning the period between January 2001 and February 2016 for diagnoses of PIIVDC. Patient age, sex, symptoms, and history and physical and neurologic findings were reviewed. Laboratory and imaging findings, management, follow-up, and outcome also were studied. RESULTS: Nine cases of PIIVDC were identified; they included 6 male and 3 female patients, with an age range of 23 months to 12 years. Two patients were asymptomatic, and PIIVDC was discovered incidentally. Of the remaining 7 patients, 5 presented with neck and/or back pain, 1 with painless torticollis, and 1 with painful torticollis. One patient reported neurologic symptoms of pain radiating along 1 dermatome. Disc spaces affected were 5 cervical, 4 thoracic, and 2 lumbar, with 2 patients having more than 1 space affected. All patients were managed conservatively. In 1 case, symptoms and lesions persisted after 5 years, but the remainder had complete symptom resolution, generally within 6 months. CONCLUSIONS: The etiology of PIIVDC remains unknown but appears to occur spontaneously, without preceding trauma or underlying medical condition. A conservative approach to patients without severe neurologic deficit with outpatient follow-up is supported.

Disc degeneration induces a mechano-sensitization of disc afferent nerve fibers that associates with low back pain.

OBJECTIVE: We aimed to investigate mechano-sensitivity at the afferent nerve fibers projecting to degenerated intervertebral disc (IVD) and nociceptive behaviour in a rat model of low back pain (LBP). DESIGN: Animal model with LBP was established by lumbar 4/5 IVD puncture and nucleus pulposus aspiration. In vivo single nerve recordings (n = 121) were introduced to measure discharge frequency at the afferent nerve fiber innervating the IVD during mechanical stimulations (von Frey filament or intradiscal pressure). Nerve growth factor (NGF) expression levels in the IVD (n = 20) were assessed by Western blot. LBP-related behaviour (n = 22) was assessed by measuring changes in rearing, mechanical paw-withdrawal threshold, and dynamic weight bearing in a freely walking rat. Inhibitory effect of morphine on the neuronal excitability (n = 19) and painful behaviour (n = 28) was also assessed. RESULTS: Compared to those with sham or naïve IVD, animal group with degenerated IVD displayed the sensitized neuronal responses and painful behaviour, with hyperexcitability of the afferent nerve fibers in any range of mechanical stimulations (von Frey filament stimulation; 1, 2, and 26 g; intradiscal pressure, 1,500-3,000 mm Hg), strong upregulation of NGF (200-250 % increase), and LBP-like behaviour such as failure of rearing, front limbs-dependent walking pattern, and hypersensitivity in hind-paws. However, the neuronal hyperexcitability and pain behaviour were attenuated after local (30 µM) or systemic (3 mg kg-1) morphine administration. CONCLUSIONS: Our study suggests that enhanced mechano-sensitivity at the afferent nerve fiber innervating degenerated IVD is deeply correlated with LBP development, which supports the hypothesis that hyperexcited responses at the nerve fibers represent a decisive source of LBP.

Stem Cell Therapies for Treatment of Discogenic Low Back Pain: a Comprehensive Review.

PURPOSE OF REVIEW: Discogenic low back pain (DLBP) stems from pathology in one or more intervertebral discs identified as the root cause of the pain. It is the most common type of chronic low back pain (LBP), representing 26-42% of attributable cases. RECENT FINDINGS: The clinical presentation of DLBP includes increased pain when sitting, coughing, or sneezing, and experiencing relief when standing or ambulating. Dermatomal radiation of pain to the lower extremity and neurological symptoms including numbness, motor weakness, and urinary or fecal incontinence are signs of advanced disease with disc prolapse, nerve root compression, or spinal stenosis. Degenerative disc disease is caused by both a decrease in disc nutrient supply causing decreased oxygen, lowered pH, and lessened ability of the intervertebral disc (IVD) to respond to increased load or injury; moreover, changes in the extracellular matrix composition cause weakening of the tissue and skewing the extracellular matrix's (ECM) harmonious balance between catabolic and anabolic factors for cell turnover in favor of catabolism. Thus, the degeneration of the disc causes a shift from type II to type I collagen expression by NP cells and a decrease in aggrecan synthesis leads to dehydrated matrix cells ultimately with loss of swelling pressure needed for mechanical support. Cell-based therapies such as autologous nucleus pulposus cell re-implantation have in animal models and human trials shown improvements in LBP score, retention of hydration in IVD, and increased disc height. Percutaneously delivered multipotent mesenchymal stem cell (MSC) therapy has been proposed as a potential means to uniquely ameliorate discogenic LBP holistically through three mechanisms: mitigation of primary nociceptive disc pain, slow or reversal of the catabolic metabolism, and restoration of disc tissue. Embryonic stem cells (ESCs) can differentiate into cells of all three germ layers in vitro, but their use is hindered related to ethical concerns, potential for immune rejection after transplantation, disease, and teratoma formation. Another similar approach to treating back pain is transplantation of the nucleus pulposus, which, like stem cell therapy, seeks to address the underlying cause of intervertebral disc degeneration by aiming to reverse the destructive inflammatory process and regenerate the proteoglycans and collagen found in healthy disc tissue. Preliminary animal models and clinical studies have shown mesenchymal stem cell implantation as a potential therapy for IVD regeneration and ECM restoration via a shift towards favorable anabolic balance and reduction of pain.