Treatment of the degenerated intervertebral disc; closure,repair and regeneration of the annulus fibrosus

Degeneration of the intervertebral disc (IVD) and disc herniation are two causes of low back pain. The aetiology of these disorders is unknown, but tissue weakening, which primarily occurs due to inherited genetic factors, ageing, nutritional compromise and loading history, is the basic factor causing disc degeneration. Symptomatic disc herniation mainly causes radicular pain. Current treatments of intervertebral disc degeneration and low back pain are based on alleviating the symptoms and comprise administration of painkillers or surgical methods such as spinal fusion. None of these methods is completely successful. Current research focuses on regeneration of the IVD and particularly on regeneration of the nucleus pulposus. Less attention has been directed to the repair or regeneration of the annulus fibrosus, although this is the key to successful nucleus pulposus, and therewith IVD, repair. This review focuses on the importance of restoring the function of the annulus fibrosus, as well as on the repair, replacement or regeneration of the annulus fibrosus in combination with restoration of the function of the nucleus pulposus, to treat low back pain. Copyright © 2014 John Wiley & Sons, Ltd.     

Healing of painful intervertebral discs: implications for physiotherapy

Abstract

Background: Population studies show close associations between intervertebral disc degeneration and back pain, with structural changes such as annulus tears being most closely related to pain. However, little effort has been made to link back pain to disc injury in individual patients, or to treat the disc injury in a similar way to a ligament or tendon sprain.

Objectives: To re-interpret the scientific literature in order to provide a rationale for physical therapy treatments that aim to promote ‘disc healing’.

Major Findings: Intervertebral discs deteriorate over many years, from the nucleus outwards, to an extent that is influenced by genetic inheritance, metabolite transport, and mechanical loading. Additionally, surgically-removed ‘painful’ human discs usually show an active inflammatory process proceeding from the outside-in. There is growing evidence that the ligamentous outer annulus can be re-innervated, and sensitized to pain by inflammatory-like responses to injury, and from displaced nucleus pulposus. Animal studies confirm that effective disc healing occurs only in the outer annulus and endplate, where cell density and metabolite transport are greatest. Identifying discogenic pain is not easy, but techniques are available. Healing of the disc periphery has the potential to relieve pain, by reducing inflammation and restoring function.

Conclusion: Physical therapies should aim to promote healing in the disc periphery, by stimulating cells, boosting metabolite transport, discouraging adhesion formation, and preventing re-injury. Such an approach, which can be applied through information sessions and classes, has the potential to bring about pain relief to large numbers of back pain sufferers through self-treatment.     

超短回波时间MRI用于腰椎间盘软骨终板成像

目的 探讨超短回波时间（UTE）MR序列及常规序列在腰椎间盘软骨终板损伤中的应用价值。方法 对87名志愿者行MR常规序列及UTE序列腰椎成像,分析UTE序列显示的腰椎间盘软骨终板损伤与椎体Modic改变、Pfirrmann椎间盘退变分级之间的相关性。结果 UTE序列成像中,椎体软骨终板显示为非钙化性软骨终板及钙化性软骨终板。L₁~S₁各节段软骨终板损伤与椎体Modic改变分型、Pfirrmann椎间盘退变分级均呈正相关（P均<0.001）。结论 与MR常规序列比较,UTE序列成像可以清楚显示腰椎间盘软骨终板分层及其损伤,且软骨终板损伤与腰椎退变存在一定关系。     

间充质干细胞移植修复椎间盘退变的研究进展

下腰痛影响了不少人的生活和工作,造成沉重的社会、经济负担。下腰痛最主要的原因是椎间盘退变,目前临床上治疗椎间盘退变的方法有保守治疗和椎体融合等手术治疗,这些方法可以缓解症状但是不针对退变的原因。通过恢复椎间盘功能来缓解疼痛的方法受到人们关注,利用组织工程学方法逆转椎间盘退变已经实现。成体间充质干细胞可以分化为髓核样细胞为椎间盘组织工程提供了种子细胞。目前这种方法初步应用于临床前研究,但是许多问题有待进一步解决,例如间充质干细胞在宿主椎间盘中如何生存和增殖,移植过程中是否需要生物支架以及移植的安全性等。     

Human umbilical cord derivatives regenerate intervertebral disc

Intervertebral disc (IVD) degeneration is characterized by the loss of nucleus pulposus (NP), which is a common cause for lower back pain. Although, currently, there is no cure for the degenerative disc disease, stem cell therapy is increasingly being considered for its treatment. In this study, we investigated the feasibility and efficacy of human umbilical cord mesenchymal stem cells (MSCs) and chondroprogenitor cells (CPCs) derived from those cells to regenerate damaged IVD in a rabbit model. Transplanted cells survived, engrafted and dispersed into NP in situ. Significant improvement in the histology, cellularity, extracellular matrix proteins, and water and glycosaminoglycan contents in IVD recipients of CPCs was observed compared to MSCs. In addition, IVDs receiving CPCs exhibited higher expression of NP‐specific human markers, SOX9, aggrecan, collagen 2, FOXF1 and KRT19. The novelty of the study is that in vitro differentiated CPCs derived from umbilical cord MSCs, demonstrated far greater capacity to regenerate damaged IVDs, which provides basis and impetus for stem cell based clinical studies to treat degenerative disc disease. Copyright © 2016 John Wiley & Sons, Ltd.     

Development of an in vitro model to test the efficacy of novel therapies for IVD degeneration

Low back pain (LBP) is a major cause of disability worldwide that has been linked to intervertebral disc (IVD) degeneration. An improved understanding of the pathogenesis of disc degeneration is now developing, which is leading to the development of a number of possible future therapies targeted at the underlying pathology and regeneration strategies. Although results thus far are promising, the investigation of such therapies in an environment that mimics the mechanical environment of the human disc in vivo is problematic. The development of an in vitro model system that can maintain metabolically active IVD tissue within a loading environment pertaining to that of the human spine is crucial for testing the efficacy of future cell‐based and tissue‐engineering therapies for IVD degeneration. Here, using our novel loading rig, capable of mimicking the loading environment experienced within the human spine, we have cultured nucleus pulposus tissue explants, applied a daily hydrostatic loading regime for up to 2 weeks and investigated proteoglycan retention, metabolic activity and cellular phenotype. IVD tissue cultured under a loading environment pertaining to the in vivo loading environment maintained metabolic cell activity, proteoglycan content and cellular phenotype. Indeed, all parameters were improved in IVD tissue cultured with load compared to unloaded controls. Such a model is invaluable for investigations assessing the feasibility and efficacy of future therapeutic approaches to inhibiting degeneration or stimulating regeneration of the IVD, where the in vivo loading environment may be crucial to their success or failure. Copyright © 2009 John Wiley & Sons, Ltd.     

Hydrogels in acellular and cellular strategies for intervertebral disc regeneration

Low back pain is an extremely common illness syndrome that causes patient suffering and disability and requires urgent solutions to improve the quality of life of these patients. Treatment options aimed to regenerate the intervertebral disc (IVD) are still under development. The cellular complexity of IVD, and consequently its fine regulatory system, makes it a challenge to the scientific community. Biomaterials‐based therapies are the most interesting solutions to date, whereby tissue engineering and regenerative medicine (TE&RM) strategies are included. By using such strategies, i.e., combining biomaterials, cells, and biomolecules, the ultimate goal of reaching a complete integration between native and neo‐tissue can be achieved. Hydrogels are promising materials for restoring IVD, mainly nucleus pulposus (NP). This study presents an overview of the use of hydrogels in acellular and cellular strategies for intervertebral disc regeneration. To better understand IVD and its functioning, this study will focus on several aspects: anatomy, pathophysiology, cellular and biomolecular performance, intrinsic healing processes, and current therapies. In addition, the application of hydrogels as NP substitutes will be addressed due to their similarities to NP mechanical properties and extracellular matrix. These hydrogels can be used in cellular strategies when combined with cells from different sources, or in acellular strategies by performing the functionalization of the hydrogels with biomolecules. In addition, a brief summary of therapies based on simple injection for primary biological repair will be examined. Finally, special emphasis will focus on reviewing original studies reporting on the use of autologous cells and biomolecules such as platelet‐rich plasma and their potential clinical applications. Copyright © 2011 John Wiley & Sons, Ltd.     

Investigation of different cell types and gel carriers for cell‐based intervertebral disc therapy,in vitro and in vivo studies

Biological treatment options for the repair of intervertebral disc damage have been suggested for patients with chronic low back pain. The aim of this study was to investigate possible cell types and gel carriers for use in the regenerative treatment of degenerative intervertebral discs (IVD). In vitro: human mesenchymal cells (hMSCs), IVD cells (hDCs), and chondrocytes (hCs) were cultivated in three gel types: hyaluronan gel (Durolane®), hydrogel (Puramatrix®), and tissue‐glue gel (TISSEEL®) in chondrogenic differentiation media for 9 days. Cell proliferation and proteoglycan accumulation were evaluated with microscopy and histology. In vivo: hMSCs or hCs and hyaluronan gel were co‐injected into injured IVDs of six minipigs. Animals were sacrificed at 3 or 6 months. Transplanted cells were traced with anti‐human antibodies. IVD appearance was visualized by MRI, immunohistochemistry, and histology. Hyaluronan gel induced the highest cell proliferation in vitro for all cell types. Xenotransplanted hMSCs and hCs survived in porcine IVDs for 6 months and produced collagen II in all six animals. Six months after transplantation of cell/gel, pronounced endplate changes indicating severe IVD degeneration were observed at MRI in 1/3 hC/gel, 1/3 hMSCs/gel and 1/3 gel only injected IVDs at MRI and 1/3 hMSC/gel, 3/3 hC/gel, 2/3 gel and 1/3 injured IVDs showed positive staining for bone mineralization. In 1 of 3 discs receiving hC/gel, in 1 of 3 receiving hMSCs/gel, and in 1 of 3 discs receiving gel alone. Injected IVDs on MRI results in 1 of 3 hMSC/gel, in 3 of 3 hC/gel, in 2 of 3 gel, and in 1 of 3 injured IVDs animals showed positive staining for bone mineralization. The investigated hyaluronan gel carrier is not suitable for use in cell therapy of injured/degenerated IVDs. The high cell proliferation observed in vitro in the hyaluronan could have been a negative factor in vivo, since most cell/gel transplanted IVDs showed degenerative changes at MRI and positive bone mineralization staining. However, this xenotransplantation model is valuable for evaluating possible cell therapy strategies for human degenerated IVDs. Copyright © 2011 John Wiley & Sons, Ltd.     

Lumbar extension exercises in conjunction with mechanical traction for the management of a patient with a lumbar herniated disc

ABSTRACT

Low back pain resulting from lumbar disc herniation is a common reason for referral for physical therapy. There is no evidence to support the management of lumbar disc herniation and derangement using mechanical traction combined with lumbar extension exercises. Therefore, the purpose of this case report was to describe and discuss the use of mechanical traction in conjunction with lumbar extension exercises for a patient with a lumbar herniated disc. The patient was a 49-year-old male referred to physical therapy with a medical diagnosis of a lumbar herniated disc at L5-S1 with compression of the L5 nerve root confirmed by MRI. The patient's chief complaint was pain over the left lumbosacral and central lumbar region with radiating pain into the left buttock accompanied by numbness and tingling in the left lower leg and foot. The patient was seen for a total of 14 visits. The first 5 days (2 weeks) of therapy consisted of lumbar extension exercises. For the following nine visits (over a 3-week period), mechanical traction was added as an adjunct to the extension exercises. Outcome measures included the Oswestry Disability Questionnaire, Back Pain Function Scale (BPFS), and the Numeric Pain Rating Scale (NPRS). Results from initial evaluation to discharge (Oswestry: 36% to 0%; BPFS: 33/60 to 57/60; NPRS: 7/10 to 0/10) demonstrated that the patient no longer experienced low back pain and improved in terms of functional status and pain-related disability. The patient no longer complained of numbness and tingling in the left lower extremity and the goals for the patient had been attained. The data from this case report suggests lumbar extension exercises in conjunction with mechanical traction facilitated the patient's improvement in pain and return to prior level of function.     

瑞士球运动治疗对腰椎间盘突出症患者疼痛和肌力的影响

目的:探讨瑞士球运动康复治疗对腰椎间盘突出症患者临床疗效和腰椎稳定性的影响。方法:30例非急性期腰椎间盘突出症患者,按性别和就诊次序依次分成对照组和运动组。选用Roland-Morris问卷（RMQ）和视觉模拟疼痛评分（VAS）,在治疗前、2周后和4周后分别进行疼痛、腹、腰背肌力评定。运动组采用瑞士球运动治疗和牵引治疗。对照组采用牵引治疗。结果:与治疗前相比,对照组和运动组4周后 RMQ 和VAS评分显著降低（P<0.05,P<0.01）;与对照组相比,运动组2周后、4周后的RMQ和VAS评分显著降低（P<0.05,P<0.01）。与对照组相比,运动组2周后、4周后腹、腰背肌力增强（P<0.05,P<0.01）。结论：瑞士球运动治疗结合腰椎牵引能显著缓解腰椎间盘突出症患者腰腿痛症状,增强腹、腰背肌力和腰椎的稳定性。     

Noninvasive multimodal fluorescence and magnetic resonance imaging of whole-organ intervertebral discs

Low back pain (LBP) is a commonly experienced symptom posing a tremendous healthcare burden to individuals and society at large. The LBP pathology is strongly linked to degeneration of the intervertebral disc (IVD), calling for development of early-stage diagnostic tools for visualizing biomolecular changes in IVD. Multimodal measurements of fluorescence molecular tomography (FMT) and magnetic resonance imaging (MRI) were performed on IVD whole organ culture model using an in-house built FMT system and a high-field MRI scanner. The resulted multimodal images were systematically validated through epifluorescence imaging of the IVD sections at a microscopic level. Multiple image contrasts were exploited, including fluorescence distribution, anatomical map associated with T1-weighted MRI contrast, and water content related with T2 relaxation time. The developed multimodality imaging approach may thus serve as a new assessment tool for early diagnosis of IVD degeneration and longitudinal monitoring of IVD organ culture status using fluorescence markers.     

综合康复疗法对腰椎间盘突出症的作用

BACKGROUND:Conservative therapy is very important in treatment of lumbar protrusion of lumbar intervertebral disc and symptoms can be alleviated or disappear in most patients by physical therapy,traction and other comprehensive methods.     

Regeneration of nucleus pulposus tissue in an ovine intervertebral disc degeneration model by cell‐free resorbable polymer scaffolds

Degeneration of intervertebral discs (IVDs) occurs frequently and is often associated with lower back pain. Recent treatment options are limited and treat the symptoms rather than regenerate the degenerated disc. Cell‐free, freeze‐dried resorbable polyglycolic acid (PGA)–hyaluronan implants were used in an ovine IVD degeneration model. The nucleus pulposus of the IVD was partially removed, endoscopically. PGA–hyaluronan implants were immersed in autologous sheep serum and implanted into the disc defect. Animals with nucleotomy only served as controls. The T2‐weighted/fat suppression sequence signal intensity index of the operated discs, as assessed by magnetic resonance imaging (MRI), showed that implantation of the PGA–hyaluronan implant improved (p = 0.0066) the MRI signal compared to controls at 6 months after surgery. Histological analysis by haematoxylin and eosin and safranin O staining showed the ingrowth of cells with typical chondrocytic morphology, even cell distribution, and extracellular matrix rich in proteoglycan. Histomorphometric analyses confirmed that the implantation of the PGA–hyaluronan scaffolds improved (p = 0.027) the formation of regenerated tissue after nucleotomy. Disc heights remained stable in discs with nucleotomy only as well as after implantation of the implant. In conclusion, implantation of cell‐free polymer‐based implants after nucleotomy induces nucleus pulposus tissue regeneration and improves disc water content in the ovine model. Copyright © 2012 John Wiley & Sons, Ltd.     

Fabrication of a novel whole tissue-engineered intervertebral disc for intervertebral disc regeneration in the porcine lumbar spine

Tissue-engineered intervertebral discs (IVDs) have been proposed as a useful therapeutic strategy for the treatment of intervertebral disc degeneration (IDD). However, most studies have focused on fabrication and assessment of tissue-engineered IVDs in small animal models and the mechanical properties of the scaffolds are far below those of native human IVDs. The aim of this study was to produce a novel tissue-engineered IVD for IDD regeneration in the porcine lumbar spine. Firstly, a novel whole tissue-engineered IVD scaffold was fabricated using chitosan hydrogel to simulate the central nucleus pulposus (NP) structure, surrounded with a poly(butylene succinate-co-terephthalate) (PBST) fiber film for inner annulus fibrosus (IAF). And, a poly(ether ether ketone) (PEEK) ring was used to stimulate the outer annulus fibrosus (OAF). Then, the scaffolds were seeded with IVD cells and the cell-scaffold hybrids were transplanted into the porcine damaged spine and harvested at 4 and 8 weeks. In vitro cell experiments showed that IVD cells distributed and grew well in the scaffolds including porous hydrogel and PBST fibers. After implantation into pigs, radiographic and MRI images indicated that the tissue-engineered IVD construct could preserve the disc height in the case of discectomy as the normal disc height and maintain a large extracellular matrix and water content in the NP. Combined with the histological and gene expression results, it was concluded that the tissue-engineered IVD had similar morphological and histological structure to the natural IVD. Moreover, after implantation for 8 weeks, the tissue-engineered IVD showed a good compressive stress and elastic moduli, approaching those of natural porcine IVD. Therefore, the prepared tissue-engineered IVD construct had similar morphological and biofunctional properties to the native tissue. Also, the tissue-engineered IVD construct with excellent biocompatibility and mechanical properties provides a promising candidate for human IDD regeneration.

A novel whole tissue-engineered IVD consisting of a triphasic scaffold demonstrated excellent biocompatibility and mechanical properties in the porcine lumbar spine.     

Effects of neural mobilization in patients after lumbar microdiscectomy due to intervertebral disc lesion

BackgroundNeural mobilization (NM) techniques have been shown to improve the neural tissue's viscoelastic properties that may lead to recover of the function of the nerve after lumbar spine surgery. This study aimed to determine the effects of NM in addition to standard rehabilitation on lumbar and sciatic pain intensity, disability level, and quality of life in patients after receiving a microdiscectomy of the intervertebral lumbar disc (IVD).MethodsTwenty-four participants (age 41.3 ± 8.3 years old) within 3–4 weeks of a microdiscectomy of an IVD were randomly allocated to control (CTRL; n = 12) or NM group (n = 12). The CTRL group received ten standard rehabilitation sessions. The NM group received the same rehabilitation sessions with the addition of NM techniques. The intensity of lumbar and sciatic pain (visual analogue scale), disability level (Oswestry disability index), and health-related quality of life (SF-36 questionnaire) were measured before and after the intervention.ResultsWithin-group analysis revealed a significant reduction in lumbar (p < 0.05) and sciatic pain intensity (p < 0.001), disability level (p < 0.001), and improvement in the physical function and problems, vitality, emotional well-being, and pain SF-36 items (p < 0.05) in both groups. There were no statistical differences between groups in all outcomes.ConclusionA standard rehabilitation protocol alone or in combination with NM techniques are equally effective in reducing pain and disability level, as well as improving quality of life in patients after a microdiscectomy due to intervertebral lumbar disc lesion.     

Influences of spinal decompression therapy and general traction therapy on the pain,disability, and straight leg raising of patients with intervertebral disc herniation

[Purpose] The purpose of this study was to identify how spinal decompression therapy and general traction therapy influence the pain, disability, and straight leg raise (SLR) ability of patients with intervertebral disc herniation. [Subjects] The subjects were 30 patients with chronic lumbar pain who were divided into a spinal decompression therapy group (SDTG, n=15), and a general traction therapy group (GTTG, n=15). [Methods] The SDTG used a spinal decompression device, and the GTTG used a lumbar traction device. Both groups received conservative physical therapy three times a week for four weeks. A visual analog scale (VAS) was used to measure the degree of pain the patients with chronic lumbar pain. The Oswestry Disability Index (ODI) was used to measure the degree of functional disability. A goniometer was used to measure the patients’ SLR ability. [Results] Both SDTG and GTTG showed statistically significant decreases in VAS and ODI scores and a statistically significant increase in SLR angle. A comparison of the two groups found no statistically significant differences. [Conclusion] Spinal decompression therapy and general traction therapy are effective at improving the pain, disability, and SLR of patients with intervertebral disc herniation. Thus, selective treatment may be required.Key words: Spinal decompression therapy, Pain, Straight leg raise     

CT检查在牵引治疗腰椎间盘突出症中的评估作用

TherearemanykindsoftherapiestoLumbardiscprotrusion（LDP），inwhichtractionisonekindofeffectivenon－operativemethod；CTiseffectiveandpreferredexaminationmethodtodiag－noseLDP．WeanalyzedclinicalmanifestationsandCTimagesof５８lumbardiscprotrusioncasesthatwerediagnosedbyCTandtreatedwithtractiontherapybeforeandaftertreatmentandassessedfunctionoftractiontherapytoLDP．１Subjectandmethod１．１SubjectWecollected５８LDPcasesthattreatedwithtractiontherapyfromOctober１９９７toJune２００１，inclu…     

Healing of painful intervertebral discs: implications for physiotherapy Part 2 — pressure change therapy: a proposed clinical model to stimulate disc healing

Abstract

Background: In Part 1 of this paper, we presented a comprehensive review of the literature, regarding pathophysiology of discogenic pain. Based on the evidence presented, we are suggesting clinical, self-management strategies to promote disc healing and treat disc pain in general.

Objectives: To suggest a physical therapy protocol for self-management of disc injuries and stimulation of disc healing.

Major findings: Inflammatory process after injury to the outer annulus is the most likely source of discogenic pain. Annulus is the tensile load bearing ‘skin’ of the disc and its histology and pathology are similar to other collagen tissues like tendons and ligaments. Conventional physiotherapy wisdom for the management of tendon and ligament injuries is applicant to annular tears. Disc pain without injury is common due to development of stress concentrations in the disc especially during prolonged, end-range postures. Spinal motion segment depends on an optimal disc function. Strategies for management of associated pathologies like apophyseal joint pain and muscle spasm are also considered on this paper.

Conclusion: Physical therapies should aim to promote healing in the disc periphery, by stimulating cells, boosting metabolite transport, discouraging adhesion formation, and preventing re-injury. The self-treatment approach presented in this paper, can potentially provide pain relief to a large number of back pain sufferers. This approach can be applied through information sessions and classes to help deal with the widening back pain pandemic.     

Physiological rationales of physical therapy interventions in the management of primary dysmenorrhea: a critical review

Abstract

Background:

The mechanisms underlying the physical therapy interventions for obtaining relief from primary dysmenorrhea (PD) symptoms are not fully understood.

Objective:

To provide an overview of the physiological rationales from randomized controlled trials (RCTs) on how physical therapy interventions in the management of PD might work.

Methods:

Databases CINAHL, PEDro, Embase, Web of Science, Ovid Medline, and AMED were searched from database inception to October 2014 using related terms for dysmenorrhea and physical therapy interventions. Trials were independently selected and data extracted by two reviewers.

Results:

The search yielded 287 citations; 26 RCTs met the inclusion criteria and were included for review. Among the 26 included trials, eight trials on acupressure, seven on acupuncture, and five on TENS, two on spinal manipulation, one on low-level light therapy (LLLT), one on heat, one on far-infrared ray, and one on yoga were identified. The predominant physiological rationales identified in the RCTs are endogenous opioid mechanisms (n?=?12), gate-control theory (n?=?8), and traditional Chinese medicine (TCM) theory (n?=?6). A few trials reported up to four different rationales.

Conclusions:

The analgesic effect of acupuncture is primarily through the release of endogenous opioids and hormones. In addition, practitioners of TCM believe that acupuncture alleviates pain of PD by regulating the prostaglandin levels. Acupressure, heat, high frequency transcutaneous electrical nerve stimulation (TENS), and yoga are proposed to work by segmental inhibition of pain pathway.