Discogenic Low Back Pain Research Articles

Microfluidic Disc-on-a-Chip Device for Mouse Intervertebral Disc-Pitching a Next-Generation Research Platform To Study Disc Degeneration.

Low back pain is the most common cause of disability worldwide, and intervertebral disc degeneration is a major cause of low back pain. Unfortunately, discogenic low back pain is often treated with symptomatic relief interventions, as no disease-modifying medications are yet available. Both to-be-deciphered disc biology/pathology and inadequate in vitro research platform are major hurdles limiting drug discovery progress for disc degeneration. Here, we developed a microfluidic disc-on-a-chip device tailored for mouse disc organ as an in vitro research platform. We hypothesize that continuous nutrients empowered by a microfluidic device would improve biological performance of cultured mouse discs compared to those in static condition. This device permitted continuous media flow to mimic in vivo disc microenvironment. Intriguingly, mouse discs cultured on the microfluidic device exhibited much higher cell viability, better preserved structure integrity and anabolic-catabolic metabolism in both nucleus pulposus and annulus fibrosus, for up to 21 days compared to those in static culture. This first "disc-on-a-chip" device lays groundwork for future preclinical studies in a relative long-term organ culture given the chronic nature of intervertebral disc degeneration. In addition, this platform is readily transformable into a streamlined in vitro research platform to recapitulate physiological and pathophysiological microenvironment to accelerate disc research.

Platelet-rich plasma in the management of chronic low back pain: a critical review.

Low back pain (LBP) is now regarded as the first cause of disability worldwide and should be a priority for future research on prevention and therapy. Intervertebral disc (IVD) degeneration is an important pathogenesis of LBP. Platelet-rich plasma (PRP) is an autologous blood concentrate that contains a natural concentration of autologous growth factors and cytokines and is currently widely used in the clinical setting for tissue regeneration and repair. PRP has great potential to stimulate cell proliferation and metabolic activity of IVD cells in vitro. Several animal studies have shown that the injection of PRP into degenerated IVDs is effective in restoring structural changes (IVD height) and improving the matrix integrity of degenerated IVDs as evaluated by magnetic resonance imaging (MRI) and histology. The results of this basic research have shown the great possibility that PRP has significant biological effects for tissue repair to counteract IVD degeneration. Clinical studies for evaluating the effects of the injection of PRP into degenerated IVDs for patients with discogenic LBP have been reviewed. Although there was only one double-blind randomized controlled trial, all the studies reported that PRP was safe and effective in reducing back pain. While the clinical evidence of tissue repair of IVDs by PRP treatment is currently lacking, there is a great possibility that the application of PRP has the potential to lead to a feasible intradiscal therapy for the treatment of degenerative disc diseases. Further large-scale studies may be required to confirm the clinical evidence of PRP for the treatment of discogenic LBP.

A multicenter randomized controlled trial on the efficacy of intradiscal methylene blue injection for chronic discogenic low back pain: the IMBI study.

A study published in PAIN in 2010 showed remarkable effects of intradiscal methylene blue (MB) injections compared with placebo on pain intensity in patients with chronic discogenic low back pain (CD-LBP). Both groups received lidocaine hydrochloride injections for pain associated with the procedure. We replicated the design of the previously published study and performed a multicenter, double-blind, randomized, placebo-controlled trial to assess whether the extraordinary effects of MB on pain intensity could be confirmed. The primary outcomes were treatment success defined as at least 30% reduction in pain intensity and the Patients' Global Impression of Change 6 months after the intervention. We included 84 patients with CD-LBP of which 14 (35%) in the MB plus lidocaine group showed treatment success compared with 11 (26.8%) in the control group who received placebo plus lidocaine (P = 0.426). Twenty-seven percent of all participants treated with MB stated that their overall health improved much or very much (Patients' Global Impression of Change), vs 25.6% in the placebo group (P = 0.958). We were unable to confirm that intradiscal MB injections are better capable of significantly reducing pain in patients with CD-LBP 6 months after treatment compared with placebo. We observed that over one-quarter of patients receiving only lidocaine injections reported treatment success, which is in contrast with the previously published study. Our results do not support the recommendation of using intradiscal MB injections for patients with CD-LBP.

Thermal Annuloplasty Using Percutaneous Endoscopic Discectomy for Elite Athletes with Discogenic Low Back Pain.

The purpose of this study was to assess the usefulness of radiofrequency thermal annuloplasty (TA) using percutaneous endoscopic discectomy/TA (PED/TA) in elite athletes with discogenic low back pain. Twelve patients (11 men, 1 woman; mean age 27.9 years) underwent PED/TA under local anesthesia. Clinical data for these patients (17 affected intervertebral discs), including type of sport played, average duration of low back pain, disc level affected, presence or absence of a high signal intensity zone on magnetic resonance imaging, and whether the patient returned to playing competitive sport, were retrospectively reviewed. The most common sport played by the patient was baseball (n = 8), followed by cycling (n = 2), tennis (n = 1), and hammer throw (n = 1). The average duration of low back pain was 24.3 months. The intervertebral disc levels affected were L4/5 (n = 11) and L5/S1 (n = 6). A high signal intensity zone was detected in nine discs. Although two patients required additional surgery, all patients were able to return to their original competitive level of play. Duration for the return to play was 2.8 months after surgery except the two revision cases. PED/TA for discogenic pain enables an early return to competitive sports, and so is particularly useful for elite athletes.

Management of Discogenic Lumbar Pain with Intradiscal Electrothermal Therapy (IDET)

Aim: Evaluate the effectiveness of intradiscal electrothermal therapy in treating discogenic low back pain. Methods: Using three data bases (PubMed, Cochrane and Scopus) we searched for clinical studies evaluating non-operative methods of treating discogenic back pain that were published between 2004-2012. Only systematic reviews and meta-analysis were included. Inclusion criteria: included if they met the following inclusion criteria: patients were at least 18 years of age; they were written in English and involved patients with chronic non-malignant pain who had never been surgical managed, after removal of duplicate citations only 4 articles were selected. Results: The two systematic reviews and two meta-analyzes whose objective were to establish the IDET roll in the improvement of discogenic pain, did not find statistically significant evidence to recommend this treatment. Only one study established a possible improvement of discogenic pain at 6 months with acceptable evidence quality. Conclusion: The current studies provide contradictory evidence of it benefit and it remains unclear whether these interventions confer stable long-term benefit. Thus, physicians must exercise caution in recommending this treatment for patients with discogenic chronic back pain.

Management of Discogenic Lumbar Pain with Intradiscal Electrothermal Therapy (IDET)

Aim: Evaluate the effectiveness of intradiscal electrothermal therapy in treating discogenic low back pain. Methods: Using three data bases (PubMed, Cochrane and Scopus) we searched for clinical studies evaluating non-operative methods of treating discogenic back pain that were published between 2004-2012. Only systematic reviews and meta-analysis were included. Inclusion criteria: included if they met the following inclusion criteria: patients were at least 18 years of age; they were written in English and involved patients with chronic non-malignant pain who had never been surgical managed, after removal of duplicate citations only 4 articles were selected. Results: The two systematic reviews and two meta-analyzes whose objective were to establish the IDET roll in the improvement of discogenic pain, did not find statistically significant evidence to recommend this treatment. Only one study established a possible improvement of discogenic pain at 6 months with acceptable evidence quality. Conclusion: The current studies provide contradictory evidence of it benefit and it remains unclear whether these interventions confer stable long-term benefit. Thus, physicians must exercise caution in recommending this treatment for patients with discogenic chronic back pain.

The relevance of high-intensity zones in degenerative disc disease.

The purpose of this study was to review the current understanding of high-intensity zones (HIZ) in the lumbar spine with particular attention to its imaging phenotype and clinical relevance. A review was conducted of studies related to HIZ. Particular attention was made to imaging phenotypes and classification, and its relationship with discogenic low back pain (LBP). The most current classification system of HIZ is based on location (anterior and posterior), morphology (round, fissure, vertical, rim, or giant types), and its appearance on both T1- and T2-weighted magnetic resonance imaging (MRI). HIZ are commonly manifested with disc degeneration. Hence, both conditions share similar risk factors such as the effect of frequent and prolonged disc loading. The clinical significance of HIZ however is not conclusive. Provocative discography is not sensitive (~ 70%) for eliciting a concordant pain response. Population-based studies have conflicting results regarding the prevalence (14-63%) of HIZ and its correlation with LBP. HIZ are likely a risk factor for discogenic LBP. However, its etiology and pathophysiology are not well understood. Some clinical studies suggest a link between its occurrence and LBP. However, the results are not consistent as a result of studies which are underpowered and based on heterogeneous study populations, lacking control groups, and without standardized imaging phenotypes. HIZ may be an important pain biomarker that should be further studied. With more modern MRI technology and a detailed classification system, future large-scale population studies will improve our knowledge on its role in the disc degeneration cascade and development of LBP.

Discogenic low back pain: interventional treatment

Low back pain (LBP) is one of the most common causes of disability in the adult population. A significant place in its genesis is occupied by a degenerative-dystrophic diseases of intervertebral discs. The article highlights the classification and mechanism of discogenic pain origin. Various types of interventions aredescribed for this pathology: indications, specificities of carrying out manipulations and therapeutic effects, efficiency and possible complications of procedures.

Do Regenerative Medicine Therapies Provide Long-Term Relief in Chronic Low Back Pain: A Systematic Review and Metaanalysis

Several cell-based therapies have been proposed in recent years the management of low back pain, including the injection of medicinal signaling cells or mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). However, there is only emerging clinical evidence to support their use at this time. To assess the effectiveness of MSCs or PRP injections in the treatment of low back and lower extremity pain. A systematic review and metaanalysis of the effectiveness of PRP and MSCs injections in managing low back and lower extremity pain. PubMed, Cochrane Library, US National Guideline Clearinghouse, prior systematic reviews, and reference lists. The literature search was performed from 1966 through June 2018. Randomized trials, observational studies, and case reports of injections of biologics into the disc, epidural space, facet joints, or sacroiliac joints. Data extraction and methodological quality assessment were performed utilizing Cochrane review methodologic quality assessment and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR). The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5. Twenty-one injection studies met inclusion criteria. There were 12 lumbar disc injections, 5 epidural, 3 lumbar facet joint, and 3 sacroiliac joint studies RESULTS: Evidence synthesis based on a single-arm metaanalysis, randomized controlled trials (RCTs), and observational studies, disc injections of PRP and MSCs showed Level 3 evidence (on a scale of Level I through V). Evidence for epidural injections based on single-arm metaanalysis, a single randomized controlled trial and other available studies demonstrated Level 4 (on a scale of Level I through V) evidence. Similarly, evidence for lumbar facet joint injections and sacroiliac joint injections without metaanalysis demonstrated Level 4 evidence (on a scale of Level I through V). Lack of high quality RCTs. The findings of this systematic review and single-arm metaanalysis shows that MSCs and PRP may be effective in managing discogenic low back pain, radicular pain, facet joint pain, and sacroiliac joint pain, with variable levels of evidence in favor of these techniques. Chronic low back pain, regenerative therapy, medicinal signaling or mesenchymal stem cells, platelet-rich plasma, disc injection, lumbar facet joint injections, sacroiliac joint injections.

The Impact of Chronic Discogenic Low Back Pain: Costs and Patients' Burden.

Introduction Chronic discogenic low back pain (CDP) is frequently diagnosed in patients referred to specialized pain clinics for their back pain. The aim of this study is to assess the impact of CDP both on the individual patient and on society. Materials and Methods Using the baseline records of 80 patients in a randomized trial assessing the effectiveness of a new intervention for CDP, healthcare and societal costs related to back pain are calculated. Furthermore, the impact of the condition on perceived pain, disability, health-related quality of life, Quality of life Adjusted Life Years (QALY), and QALY loss is assessed. Results Using the friction costs approach, we found that the annual costs for society are €7,911.95 per CDP patient, 51% healthcare and 49% societal costs. When using the human capital approach, total costs were €18,940.58, 22% healthcare and 78% societal costs. Healthcare costs were mainly related to pain treatment. Mean pain severity was 6.5 (0–10), and 46% suffered from severe pain (≥7/10). Mean physical limitations rate was 43.7; 13.5% of the patients were very limited to disabled. QALY loss compared to a healthy population was 64%. Discussion This study shows that in patients with CDP referred to a pain clinic, costs for society are high and the most used healthcare resources are pain therapies. Patients suffer severe pain, are physically limited, and experience a serious loss in quality of life.

The effect of standing vs. variants of the seated position on lumbar intersegmental angulation and spacing: a radiographic study of 20 asymptomatic subjects.

Pain while sitting is the primary complaint of many patients with lumbar spinal ailments, including those with discogenic low back pain and lumbar disc herniations. There has been little basic research on the different mechanical stresses that different sitting positions place on the spine. To demonstrate the effect of different sitting positions on lumbar intersegmental relationships. Twenty healthy male volunteer subjects were recruited. Lateral X-rays of the lower lumbar spine were taken in four positions: (I) relaxed lateral standing; (II) "standard" sitting position; (III) sitting on a "kneeling" chair; and (IV) unsupported sitting on a stool. Anterior and posterior disc height, disc space angulation, L1-S1 angulation and interspinous distance were measured. The L1-S1 lordotic angle in the standing position (48.8°±14.7°) was found to be statistically significantly greater than the angle measured with any of the sitting positions: the kneeling chair (34.0°±17.7°); hard-back chair (28.6°±14.3°); and the stool (16.6°±15.6°). Total average disc height (arithmetic sum of average disc heights L2-S1) in the lumbar spine varied with position: standing (40.5±7.75 mm); hard-back chair (38.5±6.9 mm); kneeling chair (38.4±7.9 mm); stool (36.9±7.1 mm). The mean interspinous distance over all the lumbar levels was significantly greater in each of the three seated positions than in the standing position: standing 6.8±4.5 mm; 11.6°±7.5° for the kneeling chair; 12.9±5.8 mm for the hard-back chair; 16.9±7.0 mm for the stool. If segmental flexion and segmental loading are the important biomechanical correlates of pain on sitting, such patients should be most comfortable in a kneeling chair, which most closely approximates the standing position. These basic findings will allow better assessment of different seating positions from an ergonomic perspective, and hopefully lead to improvements in chair design.

Intradiscal Methylene Blue Injection for Discogenic Low Back Pain: A Meta-Analysis.

The purpose of this study was to assess the effects of intradiscal methylene blue (MB) injection on discogenic low back pain (DLBP). We conducted an electronic search of the PubMed, Ovid, Ovid MEDLINE and Embase databases using the search terms "low back pain" and "methylene blue"; the search was limited to English language articles from database inception to October 2017. In addition, the reference lists of all included studies were manually searched. Two reviewers independently assessed the quality of the studies, extracted data from the included studies, and analyzed the data. Five studies were included. The results of the meta-analysis indicated that the effects of intradiscal MB injection between preoperation and postoperation on DLBP were statistically significant based on the 3-month visual analog scale (VAS) or numeric rating scale (NRS) (weighted mean difference [WMD]=3.61; 95% confidence interval [CI]: 2.46 to 4.76; P<0.05) and Oswestry Disability Index (ODI) (WMD=24.64, 95% CI: 12.07 to 37.21, P<0.05), the 6-month VAS or NRS (WMD=2.95; 95% CI: 1.20 to 4.71; P<0.05) and ODI (WMD=23.21, 95% CI: 12.89 to 33.53, P<0.05), and the 12-month VAS or NRS (WMD=3.19; 95% CI: 0.99 to 5.40; P<0.05) and ODI (standard mean difference=29.51, 95% CI: 20.60 to 38.42, P<0.05). Intradiscal MB injection can reduce pain severity and improve the ODI score in individuals with discogenic low back pain. Although intradiscal MB injection seems to be a safe and effective treatment for discogenic low back pain, the clinical benefits for patients with discogenic low back pain need to be further appraised in larger samples and more in-depth studies.

Friday, September 28, 2018 1:00 PM–2:30 PM abstracts: a new look at imaging: 203. Analysis of chronic low back pain with magnetic resonance imaging T2 mapping of lumbar intervertebral disc

Friday, September 28, 2018 1:00 PM–2:30 PM abstracts: a new look at imaging: 203. Analysis of chronic low back pain with magnetic resonance imaging T2 mapping of lumbar intervertebral disc

Friday, September 28, 2018 1:00 PM–2:30 PM abstracts: a new look at imaging: 207. Noninvasive MR spectroscopy (MRS) of lumbar discs correlates with surgery outcomes in discogenic low back pain (DLBP) patients

BACKGROUND CONTEXT We previously showed that MRS+/− determinations of relative discogenic pain chemical biomarker levels correlates with provocative discography results (PD+/−) for painful (P) versus nonpainful (NP) discs in chronic, severe DLBP patients. PURPOSE This current study extends our previous work, and further evaluates if MRS+/− disc data predicts lumbar surgery (Sx) outcomes in DLBP patients. STUDY DESIGN/SETTING A single-center, nonsignificant risk investigational clinical development study was conducted under IRB approval and patient informed consent for developing and evaluating MRS techniques against gold standard controls for DLBP diagnosis and surgical success. PATIENT SAMPLE A total of 129 LBP patients with 262 discs receiving PD (118 PD+, 144 PD−), 22 discs that were physician-diagnosed painful by non-PD criteria (Dx+), and 607 discs receiving MRS. 81 PD+ (plus 14 Dx+) and 101 PD- discs served as P and NP controls, after excluding 73 discs for voxels failing optimal geometry (≥1cc, ≤4mm height) and 15 discs for poor spectral quality.A total of 65 patients (plus 4 technical exclusions) also received lumbar spine Sx by one of the authors (MG) at P disc levels, with two exceptions treated at NP discs that were MRS+. OUTCOME MEASURES Surgery outcomes were evaluated at 6 and 12 months post-Sx. Success rates (≥15 point improvement from baseline Oswestry Disability Index) were compared between patient sub-groups classified by MRS+/mild/− pre-Sx results for the treated and nontreated discs. METHODS PD (generally SIS guidelines) and Sx were performed, and discs were prescribed for MRS, per physician discretion. MR spectroscopy was performed via a custom protocol using a commercial Siemens MRS pulse sequence and 3T Verio MR scanner. Investigational postprocessing software enhanced spectral quality and calculated the biomarkers and scoring algorithms. Acid: matrix biomarker ratios were used to derive degenerative pain scores: MRS-SCORE Total and Normalized (to highest Total in-patient). MRS-SCORE ranges (high=MRS+, low=MRS−) were trained to correlate to the P and NP discs (MRSmild=intermediate). Standard statistics were calculated, with 10-fold repeat cross-validation performed for generalizability. RESULTS MRS-SCORES differed significantly between P and NP discs (p CONCLUSIONS Noninvasive, objective, quantitative MRS-SCORES and MRS+/− results accurately distinguish P from NP discs, especially in nonherniated axial LBP patients. 6-12 month Sx success rates were very high when treating all MRS+ discs in patients, but low when treating MRS- discs or leaving MRS+ discs untreated. These data suggest a valuable new approach to help doctors, in combination with other available information, better diagnose and evaluate treatment options toward more successful outcomes in DLBP patients.

Comparison of percutaneous intradiscal ozone injection with laser disc decompression in discogenic low back pain.

BackgroundIntervertebral disc herniation with the pressure on the surrounding neural structures is one of the most important causes of chronic low back pain, which sometimes leads to open surgery. Reducing the pressure inside the disc with intradiscal intervention such as laser irradiation or ozone injection is a minimally invasive method and an alternative to surgery with satisfactory results. These two methods were compared with each other in this research.Patients and methodsIn this clinical trial, 40 patients with back pain radiating to lower limb due to lumbar intervertebral disc herniation were selected. These patients were randomly divided into two equal groups for percutaneous intradiscal intervention. The Laser Disc Decompression Group (LDG) (n=20) was exposed to 1500 J of laser irradiation into the disc center. In the Ozone Injection Group (OZG) patients (n=20), 6 mL of ozone 30 µg/mL was injected into the center of the disc. Considering the level of neural root involvement, both groups received 20 mg of triamcinolone injection via transforaminal epidural. Patients were followed up for 12 months regarding score on visual analogue scale and life performance improvement based on Oswestry Disability Index (ODI) and satisfaction level.ResultsAccording to the results, no difference was found between the two groups for ODI variable before intervention, whereas OZG showed better ODI scores in the measured time intervals. In LDG, only a significant difference in terms of ODI score was found between the times of before surgery and the first month.ConclusionIntradiscal ozone injection could be an effective and cost-effective method for treatment of patients with discogenic back pain.

Delayed onset of persistent discogenic axial and radiating pain after a single-level lumbar intervertebral disc injury in mice.

Low back pain (LBP) is associated with both axial discomfort and radiating leg pain. Although intervertebral discs are suspected as the source of pain in some individuals, the relationship between disc degeneration and back pain remains controversial. The goals of this study were to investigate the long-term impact of L4/L5 disc puncture on disc degeneration and the subsequent emergence, persistence, and underlying mechanisms of axial and radiating LBP in mice. L4 to L5 discs were punctured on the ventral aspect with a 30 gauge needle in 3-month old female CD1 mice, and the development of behavioral signs of axial discomfort (tail suspension and grip force), radiating hypersensitivity (von Frey and acetone), and motor impairment (rotarod) were monitored. Disc degeneration was assessed using X-ray, T2-magnetic resonance imaging, and histology, and persisted for up to 1 year. Innervation was quantified by immunohistochemistry using the pan-neuronal marker PGP9.5. Behavioural signs of axial discomfort peaked 3 to 9 months after injury. During the peak, local nerve density was increased. A transient increase in hypersensitivity to cold, suggestive of radiating pain, was observed 2 weeks after injury. Radiating pain then reemerged 9 to 12 months after injury in half the animals and correlated with increased dorsal innervation and reduced disc height at these late time points. In summary, a single-level disc injury is sufficient to induce prolonged disc degeneration and delayed axial and radiating pain. This model will be useful to investigate underlying mechanisms and potential therapeutic strategies for discogenic LBP.

MicroRNA-194 Inhibits Lipopolysaccharide-Induced Inflammatory Response in Nucleus Pulposus Cells of the Intervertebral Disc by Targeting TNF Receptor-Associated Factor 6 (TRAF6).

BackgroundThe dramatic increase of intervertebral disc degeneration (IDD) is considered to be a major cause of discogenic low back pain. The current study focused on the regulatory function of microRNA-194 (miR-194) on lipopolysaccharide (LPS)-induced inflammatory response in nucleus pulposus (NP) cells.Material/MethodsLPS was used to treat NP cells to induce inflammatory responses. MiRNA and gene expression were detected by quantitative PCR. Proteins and protein expression levels were detected by Western blot and ELISA kit. Dual luciferase reporter assay was applied to identify the correlation between an miR-194- and TNF receptor-associated factor 6 (TRAF6) and to test NF-κB activity.ResultsMiR-194 expression was reduced in LPS-induced NP cells. Both miR-194 overexpression and miR-194 inhibitor could regulate extracellular matrix (ECM) genes expression (Aggrecan and collagen II), MMP3, MMP13, ADAMTS4, and ADAMTS5, as well as inflammatory cytokines-associated genes (TNF-α, IL-1, IL-6, PGE2). Through a further study of the molecular mechanism, miR-194 was proved to be involved in the regulation of TRAF6 and its downstream signal molecule, nuclear factor-kappa B (NF-κB).ConclusionsFinding of our study suggest that miR-194 can inhibit LPS-induced inflammatory response in NP cells of the intervertebral disc (IVD) by targeting TRAF6, which may contribute development of IDD biological therapy.

Development of an in vivo mouse model of discogenic low back pain.

Discogenic low back pain (DLBP) is extremely common and costly. Effective treatments are lacking due to DLBP's unknown pathogenesis. Currently, there are no in vivo mouse models of DLBP, which restricts research in this field. The aim of this study was to establish a reliable DLBP model in mouse that captures the pathological changes in the disc and allows longitudinal pain testing. The model was generated by puncturing the mouse lumbar discs (L4/5, L5/6, and L6/S1) and removing the nucleus pulposus using a microscalpel under the microscope. Histology, molecular pathways, and pain-related behaviors were examined. Over 12 weeks post-surgery, animals displayed the mechanical, heat, and cold hyperalgesia along with decreased burrowing and rearing. Histology showed progressive disc degeneration with loss of disc height, nucleus pulposus reduction, proteoglycan depletion, and annular fibrotic disorganization. Immunohistochemistry revealed a substantial increase in inflammatory mediators at 2 and 4 weeks. Nerve growth factor was upregulated from 2 weeks to the end of the experiment. Nerve fiber ingrowth was induced in the injured discs after 4 weeks. Disc-puncture also produced an upregulation of neuropeptides in dorsal root ganglia neurons and an activation of glial cells in the spinal cord dorsal horn. These findings indicate that the cellular and structural changes in discs, as well as peripheral and central nervous system plasticity, paralleled persistent, and robust behavioral pain responses. Therefore, this mouse DLBP model could be used to investigate mechanisms underlying discogenic pain, thereby facilitating effective drug screening and development of treatments for DLBP.

Biologics for Lumbar Discogenic Pain: 18 Month Follow-up for Safety and Efficacy

The primary objective of this paper is to evaluate safety and effectiveness of platelet rich plasma (PRP) and bone marrow concentrate (BMC) injections in the lumbar intervertebral disc. The secondary objective is to evaluate utilization of health care services, hospitalization and spine surgery. A total of 20 patients with chronic (&gt; 6 months) discogenic low back pain who received intradiscal injection of either PRP or BMC were followed in this study with data on pain (Verbal Pain Scale, VPS) and function (SF-36) collected at 1, 3, 6, 12, and 18 months post-injection. Additional assessments included utilization of medications, health care services, hospitalization, and spine surgery. Of the 20 patients, 18 remained at 6 months and 15 remained at 18 months. Of those who remained, more than 50% relief in VPS was noted in 94% of patients at 6 months, and in 93% of patients at 18 months. An improvement in SF-36s physical component summary (PCS) was noted in 100% of patients at 6 months, and in 93% of patients at 18 months. There were no reported side effects or adverse reactions noted from the injections. Medication use decreased in 89% of patients at 6 months and in 80% of patients at 18 months. None of the patients presented to the emergency room, were hospitalized, or underwent surgery for the spinal area treated with the injection. This study supports the safety of a single intradiscal biologic injection and provides additional evidence for its efficacy in management of lumbar discogenic pain, with improvements in both pain and function, and decreased utilization of medications and medical services thereby decreasing health care costs. Key words: Autologous, biologics, platelet-rich plasma, bone marrow concentrate, injections, lumbar, disc, discogenic pain, regenerative medicine

Macrophage-derived inflammatory cytokines regulate growth factors and pain-related molecules in mice with intervertebral disc injury.

Upregulation of inflammatory cytokines and various growth factors is a significant contributor to discogenic low back pain. The aim of this study was to investigate possible regulation of pain-related molecules by macrophages and the role of macrophage-derived molecules in injured intervertebral disc (IVD)s. C57BL/6J mice were used in this study. We characterized the expression profiles of genes for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) in both intact and injured IVDs. We examined whether macrophage depletion, induced by systemic injection of clodronate-laden liposomes, affected the expression of these molecules in injured IVDs. The effect of TNF-alpha on cultured F4/80-CD11b-cells in injured IVDs was investigated. Expression of TNF-alpha and IL-1beta was significantly increased in injured IVDs, but decreased by macrophage depletion. Expression of NGF and VEGF was also significantly increased, but by contrast was not decreased by macrophage depletion. TNF-alpha treatment of F4/80-cells from injured IVDs upregulated NGF, VEGF, cyclooxygenase (COX)-2, and microsomal prostaglandin E synthase-1 (mPGES1). IVD injury upregulated inflammatory cytokines and various growth factors. Macrophages in the injured IVDs produced inflammatory cytokines, but not growth factors. Macrophage-derived inflammatory cytokines regulate growth factors and pain-related molecules. These findings demonstrate further complexity in the pathogenesis of discogenic pain. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.