Intervertebral disk (IVD) degeneration is a natural progression of the aging process. Degenerative disk disease (DDD) is a pathologic condition associated with IVD that has been associated with chronic back pain. There are a variety of different mechanisms of DDD (genetic, mechanical, exposure). Each of these pathways leads to a final common result of unbalancing the anabolic and catabolic environment of the extracellular matrix in favor of catabolism. Attempts have been made to gain an understanding of the process of IVD degeneration with in Vitro studies. These models help our understanding of the disease process, but are limited as they do not come close to replicating the complexities that exist with an in Vivo model. Animal models have been developed to help us gain further understanding of the degenerative cascade of IVD degeneration In Vivo and test experimental treatment modalities to either prevent or reverse the process of DDD. Many modalities for treatment of DDD have been developed including therapeutic protein injections, stem cell injections, gene therapy, and tissue engineering. These interventions have had promising outcomes in animal models. Several of these modalities have been attempted in human trials, with early outcomes having promising results. Further, increasing our understanding of the degenerative process is essential to the development of new therapeutic interventions and the optimization of existing treatment protocols. Despite limited data, biological therapies are a promising treatment modality for DDD that could impact our future management of low back pain.

Intervertebral Disk Degeneration and Repair.

Low back pain (LBP), as a leading cause of disability, is a common musculoskeletal disorder that results in major social and economic burdens. Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration, a significant contributor to LBP. Inflammatory mediators also play an indispensable role in discogenic LBP. The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies. Here, an overview of the advances in inflammation-related pain in disc degeneration is provided, with a discussion on the role of inflammation in IVD degeneration and pain induction. Puncture models, mechanical models, and spontaneous models as the main animal models to study painful disc degeneration are discussed, and the underlying signaling pathways are summarized. Furthermore, potential drug candidates, either under laboratory investigation or undergoing clinical trials, to suppress discogenic LBP by eliminating inflammation are explored. We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.

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Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions.

Substantial advancements have been made in the cause, diagnosis, imaging, and treatment options available for patients with lumbar disc herniation (LDH). We examined the current evidence and highlight the concepts on the frontline of discovery in LDH. There are a myriad of novel etiologies of LDH detailed in recent literature including inflammatory factors and infectious microbes. In the clinical setting, recent data focuses on improvements in computer tomography as a diagnostic tool and non-traditional injection options including tumor necrosis alpha inhibitors and platelet-rich plasma. Operative treatment outcomes have focused on minimally invasive endoscopic approaches and demonstrated robust 5-year post-operative outcomes. Advances in the molecular etiology of LDH will continue to drive novel treatment options. The role of endoscopic treatment for LDH will continue to evolve. Further research into10-year outcomes will be necessary as this surgical approach continues to gain widespread popularity.

Lumbar Disc Herniation.

Intervertebral disc degeneration (IVDD) is a multi-factorial process characterized by phenotypic and genotypic changes, which leads to low back pain and disability. Prolonged imbalance between anabolism and catabolism in discs alters their composition resulting in progressive loss of proteoglycans and hydration leading to IVDD. The current managements for IVDD are only able to relieve the symptoms but do not address the underlying pathology of degeneration. Researchers have tried to find out differences between the aging and degeneration of the disc. Intense attempts are in progress for identifying the various factors responsible for disc degeneration, as well as strategies for regeneration. Recently biological approaches have gained thrust in the field of IVDD. The present review illustrates the current understanding of intervertebral disc degeneration and aims to put forth recent advancements in regeneration strategies involving different biological therapies such as growth factor, cell, and gene therapy. The potentials and consequences of these therapies are also extensively discussed along with citing the most suitable method, that is, the gene therapy in detail. Initially, gene therapy was mediated by viral vectors but recent progress has enabled researchers to opt for non-virus-mediated gene therapy methods, which ensure that there are no risks of mutagenicity and infection in target cells. With constant efforts, non-virus-mediated gene therapy may prove to be an extremely powerful tool in treatment of IVDD in future.

Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review.

To present the pathophysiology, biology, clinical presentation, diagnosis, and current treatment options for lumbar disc herniation. A thorough literature search was undertaken in PubMed and Google Scholar to summarize the current knowledge and future perspectives on lumbar disc herniation. Several changes in the biology of the intervertebral disc are thought to contribute to disc herniation; nevertheless, the exact inciting event leading to disc herniation is yet to be discovered. Non-operative treatments have stood the test of time as the first-line treatment for most patients with lumbar disc herniation; however, operative treatment remains the current gold standard, with minimally invasive endoscopic microdiscectomy techniques showing best results with respect to postoperative pain and function. The exact event leading to disc herniation remains unclear. Non-operative treatments should be the first-line treatment for most patients with lumbar disc herniation. Operative treatment remains the current gold standard, with minimally invasive endoscopic microdiscectomy techniques showing best results with respect to postoperative pain and function. Regenerative medicine is promising.

Current concepts for lumbar disc herniation

Background. Platelet-rich plasma (PRP) has been found to be effective for a variety of musculoskeletal conditions. The treatment of discogenic pain with PRP is under investigation.

Objective. To assess changes in pain and function in patients with discogenic low back pain after an intradiscal injection of PRP.

Study Design. Prospective trial.

Methods. Patients were diagnosed with discogenic low back pain by clinical means, imaging, and exclusion of other structures. Provocation discography was used in a minority of the patients. Patients underwent a single treatment of intradiscal injection of PRP at one or multiple levels.

Main Outcome Measures. Patients were considered a categorical success if they achieved at least 50% improvement in the visual analog score and 30% decrease in the Oswestry Disability Index at 1, 2, and 6 months post-treatment.

Results. 22 patients underwent intradiscal PRP. Nine patients underwent a single level injection, ten at 2 levels, two at 3 levels, and one at 5 levels. Categorical success rates were as follows: 1 month: 3/22 = 14% (95% CI 0% to 28%), 2 months: 7/22 = 32% (95% CI 12% to 51%), 6 months: 9/19 = 47% (95% CI 25% to 70%).

Conclusion. This trial demonstrates encouraging preliminary 6 month findings, using strict categorical success criteria, for intradiscal PRP as a treatment for presumed discogenic low back pain. Randomized placebo controlled trials are needed to further evaluate the efficacy of this treatment.

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Intradiscal Platelet-Rich Plasma Injection for Chronic Discogenic Low Back Pain: Preliminary Results from a Prospective Trial.

Background . Lumbar transforaminal epidural steroid injections (TFESIs) are often used in the treatment of radicular pain. In light of safety concerns, many practitioners have proposed adopting the retrodiscal (infraneural) approach with the needle tip positioned into Kambin’s triangle. With this technique, the needle may inadvertently be directed too far ventrally and enter the intervertebral disc. In addition, the risk of subarachnoid or subdural extra-arachnoid injection may be higher with this technique as well.

Objective . To determine the incidence of inadvertent intradiscal, intrathecal, and vascular injections during the performance of retrodiscal TFESI.

Study Design . Retrospective review

Methods . Retrospective review of all retrodiscal approach TFESIs performed from July 2012 to August 2014 by two of the authors (DL and SH).

Results . A total of 257 retrodiscal transforaminal injections were performed. There were no neurologic complications. There were no cases of discitis. Inadvertent intradiscal injections occurred in 12/257 injections, 4.7% (95% CI 2.1–7.3%). Intrathecal injections occurred in 8/257 injections, 3.1% (95% CI 0.99– 5.23%). Three were subarachnoid (SA), four were subdural extra-arachnoid (SDXA), and one was both SA and SDXA. Vascular injections occurred in 17/257, 6.6% (95% CI 3.6–9.6%).

Conclusion . This retrospective review demonstrates that a relatively high rate of inadvertent intradiscal injections occurs in the performance of the retrodiscal approach for TFESI. This has significant implications in terms of the potential risk of disc injury induced by the needle puncture. The high incidence of intrathecal injections may also be of great concern depending upon the injectate delivered.

The Incidence of Intradiscal, Intrathecal, and Intravascular Flow During the Performance of Retrodiscal (Infraneural) Approach for Lumbar Transforaminal Epidural Steroid Injections.

Background Low back pain is a leading cause of pain and disability. The intervertebral disk has been identified as the most common source of chronic low back pain. Although prior treatments directed at intervertebral disks have been disappointing, recent studies show promising improvement of pain and function after a single intradiskal injection of methylene blue. Objective To assess changes in pain and function in patients with diskogenic low back pain, diagnosed by diskography, after an intradiskal injection of methylene blue. Study Design Prospective trial. Methods Patients diagnosed with diskogenic pain by diskography underwent a single treatment of intradiskal injection of methylene blue, determined by prior provocation diskography. Main Outcome Measures Pain and function measurements were completed at baseline and 1, 2, and 6 months after treatment. Treatment was considered a categorical success based on a 30% improvement in pain according to a visual analog scale (VAS) and function on the Oswestry Disability Index (ODI). Treatment was considered a categorical failure if less than 30% improvement in pain and function was achieved or if the patient pursued other invasive treatment options during the trial period. Results Sixteen patients received the intradiskal methylene blue injection. Eleven patients received a single-level injection, 4 patients received a 2-level injection, and one patient received injections at 3 levels. For the VAS, at 1, 2, and 6 months after the injection, the categorical success rates were 25%, 21%, and 25%, respectively. For the ODI, at 1, 2 and 6 months after the injection, the categorical success rates were 25%, 21%, and 33%, respectively. The overall categorical success rates at 1, 2, and 6 months after the injection were 19%, 21%, and 25%, respectively. Conclusion This small trial did not demonstrate overall clinical success of intradiskal methylene blue injection for patients diagnosed with diskogenic pain by diskography.

Intradiskal methylene blue treatment for diskogenic low back pain.

Objective. To present a case of inadvertent intradiscal flow during a L4/5 transforaminal epidural steroid injection.

Design. Case report.

Setting. Outpatient private practice.

Patients. Single case.

Intervention. Lumbar transforaminal epidural steroid injection.

Results. Flow of contrast indicating needle entry into extruded disc material with filling of the L4/5 disc.

Conclusion. This case demonstrates the possibility of needle entry into disc material in the presence of a large lateral disc extrusion with cephalad migration during a transforaminal epidural steroid injection.

Intradiscal Flow During a Transforaminal Epidural Steroid Injection

Background and Objective. Contralateral oblique (CLO) angle view has been a useful addition to standard views in fluoroscopically guided interlaminar epidural injections. Determination of the appropriate CLO angle is paramount in the usefulness of this technique. Using MRI laminar angle measurements as a pre-procedural guide for the intra-procedural fluoroscopic CLO angle has been proposed. The purpose of this study was to help determine if using axial MRI laminar measurements prior to a cervical or thoracic epidural steroid injection would be useful in predicting the appropriate fluoroscopic CLO angle.

Study Design. A retrospective review was performed for patients who underwent cervical or thoracic interlaminar injections. In the performance of interlaminar injections, the authors had routinely determined the true fluoroscopic contra-lateral oblique angle after epidural access was confirmed, for use during any potential future injections. The fluoroscopic CLO angle measurements were obtained from a chart review and compared blindly to each patient’s MRI axial laminar angle measurements.

Results. 34 injections were included. Inter-rater reliability comparing the two authors’ MRI angle measurements was considered fair, ICC = 0.395. Accuracy was only 57% comparing MRI laminar angle measurements to within five degrees of the true fluoroscopic CLO angle as determined during the injection procedure. Accuracy by ICC showed only fair agreement, 0.47 and 0.22, for the two authors.

Conclusions. The findings of this study indicate fair inter-rater reliability in manual measurements of laminar angle on axial MRI images. MRI laminar angle measurements do not appear to be highly accurate in determining the appropriate fluoroscopic CLO angle.

Reliability and Accuracy of MRI Laminar Angle Measurements to Determine Intra-Procedural Contralateral Oblique View Angle for Cervical or Thoracic Interlaminar Epidural Steroid Injections.

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