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      Treatment of chronic low back pain – new approaches on the horizon

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          Abstract

          Back pain is the second leading cause of disability among American adults and is currently treated either with conservative therapy or interventional pain procedures. However, the question that remains is whether we, as physicians, have adequate therapeutic options to offer to the patients who suffer from chronic low back pain but fail both conservative therapy and interventional pain procedures before they consider surgical options such as discectomy, disc arthroplasty, or spinal fusion. The purpose of this article is to review the potential novel therapies that are on the horizon for the treatment of chronic low back pain. We discuss medications that are currently in use through different phases of clinical trials (I–III) for the treatment of low back pain. In this review, we discuss revisiting the concept of chemonucleolysis using chymopapain, as the first drug in an intradiscal injection to reduce herniated disc size, and newer intradiscal therapies, including collagenase, chondroitinase, matrix metalloproteinases, and ethanol gel. We also review an intravenous glial cell-derived neurotrophic growth factor called artemin, which may repair sensory nerves compressed by herniated discs. Another new drug in development for low back pain without radiculopathy is a subcutaneous monoclonal antibody acting as nerve growth factor called tanezumab. Finally, we discuss how platelet-rich plasma and stem cells are being studied for the treatment of low back pain. We believe that with these new therapeutic options, we can bridge the current gap between conservative/interventional procedures and surgeries in patients with chronic back pain.

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          Most cited references 81

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          Intervertebral disc: anatomy-physiology-pathophysiology-treatment.

           P Prithvi Raj (2015)
          This review article describes anatomy, physiology, pathophysiology and treatment of intervertebral disc. The intervertebral discs lie between the vertebral bodies, linking them together. The components of the disc are nucleus pulposus, annulus fibrosus and cartilagenous end-plates. The blood supply to the disc is only to the cartilagenous end-plates. The nerve supply is basically through the sinovertebral nerve. Biochemically, the important constituents of the disc are collagen fibers, elastin fibers and aggrecan. As the disc ages, degeneration occurs, osmotic pressure is lost in the nucleus, dehydration occurs, and the disc loses its height. During these changes, nociceptive nuclear material tracks and leaks through the outer rim of the annulus. This is the main source of discogenic pain. While this is occurring, the degenerative disc, having lost its height, effects the structures close by, such as ligamentum flavum, facet joints, and the shape of the neural foramina. This is the main cause of spinal stenosis and radicular pain due to the disc degeneration in the aged populations. Diagnosis is done by a strict protocol and treatment options are described in this review. The rationale for new therapies are to substitute the biochemical constituents, or augment nucleus pulposus or regenerate cartilaginous end-plate or finally artificial disc implantation..
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            Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study.

            Degenerative disc disease may cause severe low-back pain, a large public health problem with significant economic and life quality impact. Chronic cases often require surgery, which may lead to biomechanical problems and accelerated degeneration of the adjacent segments. Cell-based therapies may circumvent these problems and have exhibited encouraging results in vitro and in animal studies. We designed a pilot study to assess feasibility and safety and to obtain early indications on efficacy of treatment with mesenchymal stem cells (MSC) in humans. Ten patients with chronic back pain diagnosed with lumbar disc degeneration with intact annulus fibrosus were treated with autologous expanded bone marrow MSC injected into the nucleus pulposus area. Clinical evolution was followed for 1 year and included evaluation of back pain, disability, and quality of life. Magnetic resonance imaging measurements of disc height and fluid content were also performed. Feasibility and safety were confirmed and strong indications of clinical efficacy identified. Patients exhibited rapid improvement of pain and disability (85% of maximum in 3 months) that approached 71% of optimal efficacy. This outcome compares favorably with the results of other procedures such as spinal fusion or total disc replacement. Although disc height was not recovered, water content was significantly elevated at 12 months. MSC therapy may be a valid alternative treatment for chronic back pain caused by degenerative disc disease. Advantages over current gold standards include simpler and more conservative intervention without surgery, preservation of normal biomechanics, and same or better pain relief.
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              Nerve ingrowth into diseased intervertebral disc in chronic back pain.

              In the healthy back only the outer third of the annulus fibrosus of the intervertebral disc is innervated. Nerve ingrowth deeper into diseased intervertebral disc has been reported, but how common this feature is and whether it is associated with chronic pain are unknown. We examined nerve growth into the intervertebral disc in the pathogenesis of chronic low back pain. We collected 46 samples of intervertebral discs from 38 patients during spinal fusion for chronic back pain. 30 samples were from pain levels clinically established by discography and 16 samples were from adjacent vertebral levels with no pain. We obtained 34 control samples of intervertebral disc from previously healthy individuals with normal histology within 8 h of recorded death. We used standard immunohistochemical techniques to test for a general nerve marker, a nociceptive neurotransmitter (substance P), and a protein expressed during axonogenesis (growth-associated protein 43 [GAP43]). We identified nerve fibres in the outer third of the annulus fibrosus in 48 (60%) of the 80 samples of intervertebral discs. Nerves were restricted to the outer or middle third of the annulus fibrosus in the 34 control samples. Among the patients with chronic low back pain, nerves extended into the inner third of the annulus fibrosus and into the nucleus pulposus in 21 (46%) and ten (22%) samples, respectively. Nerves usually accompanied blood vessels, but in 14 of the samples from back-pain patients, isolated nerve fibres were seen in the discal matrix. Both types of nerve fibres expressed substance P, but only non-vessel-associated fibres expressed GAP43. Deep nerve ingrowth into the inner third of the annulus fibrosus, the nucleus pulposus, or both was seen in four (25%) of 16 biopsy samples from non-pain levels and in 17 (57%) samples from pain levels. Of the 16 paired samples from both pain and non-pain levels, five pain-level samples and one non-pain-level sample showed deep nerve ingrowth. Our finding of isolated nerve fibres that express substance P deep within diseased intervertebral discs and their association with pain suggests an important role for nerve growth into the intervertebral disc in the pathogenesis of chronic low back pain.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2017
                10 May 2017
                : 10
                : 1111-1123
                Affiliations
                [1 ]Department of Anesthesiology, Advocate Illinois Masonic Medical Center
                [2 ]Department of Anesthesiology
                [3 ]Department of Surgery, University of Illinois, Chicago, IL, USA
                Author notes
                Correspondence: Nebojsa Nick Knezevic, Department of Anesthesiology, Advocate Illinois Masonic Medical Center, 836 W. Wellington Ave., Suite 4815, Chicago, IL 60657, USA, Tel +1 773 296 5619, Fax +1 773 296 5362, Email nick.knezevic@ 123456gmail.com
                Article
                jpr-10-1111
                10.2147/JPR.S132769
                5436786
                © 2017 Knezevic et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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