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.

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