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          Abstract

          Lumbar intervertebral disc (IVD) herniation causes severe low back pain (LBP), which results in substantial financial and emotional strains. Despite the effectiveness of discectomy, there is no existing treatment for post-operative LBP induced by progressive IVD degeneration. Two key factors of LBP are intradiscal inflammation, indicated by tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and sensory nerve ingrowth into the inner layer of the annulus fibrosus, triggered by nerve growth factor/high-affinity tyrosine kinase A (TrkA) signalling. In an animal models of discectomy, the bioresorbable ultra-purified alginate (UPAL) gel with an extremely low-toxicity has been effective in acellular tissue repair. We aimed to investigate whether UPAL gel can alleviate LBP using a rat nucleus pulposus (NP) punch model and a rabbit NP aspirate model. In both models, we assessed TNF-α and IL-6 production and TrkA expression within the IVD by immunohistochemistry. Further, histological analysis and behavioural nociception assay were conducted in the rat model. UPAL gel implantation suppressed TNF-α and IL-6 production, downregulated TrkA expression, inhibited IVD degeneration, and reduced nociceptive behaviour. Our results suggest the potential of UPAL gel implantation as an innovative treatment for IVD herniation by reducing LBP and preventing IVD degeneration after discectomy.

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          Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society.

          RECOMMENDATION 1: Clinicians should conduct a focused history and physical examination to help place patients with low back pain into 1 of 3 broad categories: nonspecific low back pain, back pain potentially associated with radiculopathy or spinal stenosis, or back pain potentially associated with another specific spinal cause. The history should include assessment of psychosocial risk factors, which predict risk for chronic disabling back pain (strong recommendation, moderate-quality evidence). RECOMMENDATION 2: Clinicians should not routinely obtain imaging or other diagnostic tests in patients with nonspecific low back pain (strong recommendation, moderate-quality evidence). RECOMMENDATION 3: Clinicians should perform diagnostic imaging and testing for patients with low back pain when severe or progressive neurologic deficits are present or when serious underlying conditions are suspected on the basis of history and physical examination (strong recommendation, moderate-quality evidence). RECOMMENDATION 4: Clinicians should evaluate patients with persistent low back pain and signs or symptoms of radiculopathy or spinal stenosis with magnetic resonance imaging (preferred) or computed tomography only if they are potential candidates for surgery or epidural steroid injection (for suspected radiculopathy) (strong recommendation, moderate-quality evidence). RECOMMENDATION 5: Clinicians should provide patients with evidence-based information on low back pain with regard to their expected course, advise patients to remain active, and provide information about effective self-care options (strong recommendation, moderate-quality evidence). RECOMMENDATION 6: For patients with low back pain, clinicians should consider the use of medications with proven benefits in conjunction with back care information and self-care. Clinicians should assess severity of baseline pain and functional deficits, potential benefits, risks, and relative lack of long-term efficacy and safety data before initiating therapy (strong recommendation, moderate-quality evidence). For most patients, first-line medication options are acetaminophen or nonsteroidal anti-inflammatory drugs. RECOMMENDATION 7: For patients who do not improve with self-care options, clinicians should consider the addition of nonpharmacologic therapy with proven benefits-for acute low back pain, spinal manipulation; for chronic or subacute low back pain, intensive interdisciplinary rehabilitation, exercise therapy, acupuncture, massage therapy, spinal manipulation, yoga, cognitive-behavioral therapy, or progressive relaxation (weak recommendation, moderate-quality evidence).
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            Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators.

            Herniated intervertebral disc tissue has been shown to produce a number of proinflammatory mediators and cytokines, but there have been no similar studies using discs from patients with discogenic low back pain. We have compared the levels of production of interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E2 (PGE2) in disc tissue from patients undergoing discectomy for sciatica (63) with that from patients undergoing fusion for discogenic low back pain (20) using an enzyme-linked immunoabsorbent assay. There was a statistically significant difference between levels of production of IL-6 and IL-8 in the sciatica and low back pain groups (p < 0.006 and p < 0.003, respectively). The high levels of proinflammatory mediator found in disc tissue from patients undergoing fusion suggest that production of proinflammatory mediators within the nucleus pulposus may be a major factor in the genesis of a painful lumbar disc.
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              The prevalence and clinical features of internal disc disruption in patients with chronic low back pain.

              This was a cross-sectional analytic study of patients with chronic low back pain. To investigate whether the criteria for internal disc disruption, as adopted by the International Association for the Study of Pain, could be satisfied in patients with chronic low back pain and to test whether there were any conventional clinical features that could identify this condition. Internal disc disruption has been postulated as an important cause of low back pain. To diagnose this condition, the International Association for the Study of Pain taxonomy requires that pain be reproduced on provocation discography and that computed tomography discography reveal internal disc disruption, provided that as a control, stimulation of at least one other disc fails to reproduce pain. Ninety-two consecutive patients with chronic low back pain and no history of previous lumbar surgery were studied. Each patient underwent a standard physical examination. Computed tomography discography was performed at a minimum of two levels. The diagnostic criteria for internal disc disruption were fully satisfied in 39% of patients, most commonly at L5-S1 and L4-L5. None of the clinical tests used could differentiate between those patients with internal disc disruption and other patients. A diagnosis of internal disc disruption can be made in a significant proportion of patients with chronic low back pain, but no conventional clinical test can discriminate patients with internal disc disruption from patients with other conditions.
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                Author and article information

                Contributors
                yka2q@yahoo.co.jp
                hidekisudo@yahoo.co.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                12 January 2021
                12 January 2021
                2021
                : 11
                : 638
                Affiliations
                [1 ]GRID grid.39158.36, ISNI 0000 0001 2173 7691, Department of Orthopedic Surgery, Faculty of Medicine and Graduate of Medicine, , Hokkaido University, ; N15W7, Sapporo, Hokkaido 060-8638 Japan
                [2 ]GRID grid.39158.36, ISNI 0000 0001 2173 7691, Department of Advanced Medicine for Spine and Spinal Cord Disorders, Faculty of Medicine and Graduate of Medicine, , Hokkaido University, ; N15W7, Sapporo, Hokkaido 060-8638 Japan
                Article
                79958
                10.1038/s41598-020-79958-9
                7804289
                33436742
                a04a22bc-7dc2-45bd-a380-2fdaa9fb32b5
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 5 October 2020
                : 15 December 2020
                Funding
                Funded by: Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan
                Award ID: 20K17983
                Award ID: 16H03176
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100007591, Akiyama Life Science Foundation;
                Funded by: FundRef http://dx.doi.org/10.13039/100007449, Takeda Science Foundation;
                Funded by: Mochida Pharmaceutical Co., Ltd.
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                biomaterials,cartilage,pain
                Uncategorized
                biomaterials, cartilage, pain

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