The Effects of Elgucare on Degenerated Intervertebral Disc-Induced Low Back Pain and Disc Regeneration: A Clinical Trial.

INTRODUCTION: Chronic low back pain (LBP) has a wide range of causes. However, most cases are induced by degeneration of the lumbar intervertebral discs (IVDs), and the aching caused by local compression of the affected region has considerable impacts on quality of life. This clinical trial investigated the use of Elgucare, a Chinese herbal formula, as a food supplement to reduce the pain of patients with LBP induced by degeneration of the lumbar IVDs. METHODS: The study assessed patient subjective quality of life, functional limitations caused by LBP, and variations in pain. The assessment was done through the visual analogue scale (VAS) and effects on lumbar IVD thickness, water content, and bone mineral density (BMD). These parameters were evaluated before and after the administration of Elgucare or a placebo, one of which was taken by each participant for a 12-month period. RESULTS: Elgucare reduced the patients' mean VAS pain score by 2.25 points and improved their mean LBP-hampered mobility as assessed by the Roland-Morris Questionnaire by 5.17 points. The results of another questionnaire indicated that Elgucare slowed the LBP-induced deterioration of patients' quality of life, while objective assessment indices obtained through X-ray and magnetic resonance imaging showed that the height and water retention of their IVDs were increased. However, the BMD results showed no improvements. CONCLUSIONS: Elgucare can increase the water retention and height of IVDs and reduce LBP, thereby enhancing quality of life. Therefore, Elgucare can potentially be used as a clinical supplement.

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research.

Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations' processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.

Clinical efficacy of targeted injection of drugs in combination with ozone in treatment of lumbar disc protrusion.

To investigate the clinical efficacy of targeted injection of drugs surrounding the protruded lumbar disc in combination with the ozone in treatment of lumbar disc protrusion. Between January 2017 and January 2019, a total of 120 patients with lumbar disc protrusion were recruited in this study and divided into the control group and observation group, with 60 patients in each group. Patients in the control group received the ozone treatment, while those in the observation group additionally took the targeted injection of betamethasone surrounding the protruded lumbar disc. Following one month of treatment, we compared the short-term efficacy, joint range of motion in bending forward or backward of the lumbar disc, limb function, life quality and functional disturbance before and after treatment. In the observation group, the short-term effectiveness rate was higher than that in the control group (P<0.05), while after treatment, the joint range of motion in bending forward or backward of lumbar disc in the observation group was improved when comparing to the control group (P<0.05). After treatment, BI and Fugl-Meyer scale were all higher in the observation than those in the control group (P<0.05), with a lower Oswestry score (P<0.05). Targeted injection of betamethasone surrounding the protruded lumbar disc in combination with the ozone performs well in short-term efficacy, conducive to the improvement of the lumbar disc function and limb function and alleviation in function disturbance. Thus, this strategy is worthy of being promoted in clinical practice.

The degenerative lumbar disc: not a disease, but still an important consideration for OMPT practice: a review of the history and science of discogenic instability.

BACKGROUND: A recent AAOMPT position paper was published that opposed the use of the term 'degenerative disc disease' (DDD), in large part because it appears to be a common age-related finding. While common, there are significant physiologic and biomechanical changes that occur as a result of discogenic degeneration, which are relevant to consider during the practice of manual therapy. METHODS: A narrative review provides an overview of these considerations, including a historical perspective of discogenic instability, the role of the disc as a pain generator, the basic science of a combined biomechanical and physiologic cycle of degeneration and subsequent discogenic instability, the influence of rotation on the degenerative segment, the implications of these factors for manual therapy practice, and a perspective on an evidence-based treatment approach to patients with concurrent low back pain and discogenic degeneration. CONCLUSIONS: As we consider the role of imaging findings such as DDD, we pose the following question: Do our manual interventions reflect the scientifically proven biomechanical aspects of DDD, or have we chosen to ignore the helpful science as we discard the harmful diagnostic label?

Electroacupuncture for lumbar disc herniation: A protocol for systematic review and meta-analysis.

BACKGROUND: This systematic review aims to evaluate the effectiveness of electroacupuncture in treatment of lumbar disc herniation (LDH). METHODS: Electronic databases of all electroacupuncture for LDH will be searched at PubMed, Cochrane Library, Springer, EMBASE, China National Knowledge Infrastructure (CNKI), Wan-Fang, and Chinese Biological Medical disc, (CBM) from inception to February 29, 2020, with language restricted in Chinese and English. The primary outcome is Japanese Orthopedic Association Scores, a quantification scale for a comprehensive assessment according to patients' subjects feeling and objective function. Secondary outcomes included visual analogue scale (VAS), Oswestry dysfunction index (ODI), Pittsburgh sleep quality index (PSQI), Self-rating anxiety scale (SAS), self-depression rating scale (SDS), follow-up relapse rate. The systematic review and searches for randomized controlled trials of this therapy for LDH. The Cochrane RevMan V5.3 bias assessment tool is implemented to assess bias risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). Mean difference (MD), standard mean deviation (SMD) and binary data will be used to represent continuous results. RESULTS: This study will provide a comprehensive review and evaluation of the available evidence for the treatment of LDH with this therapy. CONCLUSION: This study will provide new evidence to evaluate the effectiveness and side effects of electroacupuncture for LDH. Due to the data is not personalized, no formal ethical approval is required.

Pharmacokinetic study of eight bioactive components following oral administration of Zhiqiao Gancao decoction and observation of its clinical efficacy.

Zhiqiao Gancao (ZQGC) decoction is widely used in China due to its therapeutic effect on lumbar disc herniation (LDH). In this study, we compared the clinical therapeutic effects among oral ZQGC decoction treatment, bed rest, and oral anti-inflammatory drug celecoxib treatment using visual analog scale, Oswestry Disability Index, and MacNab scores. The results showed that ZQGC decoction can significantly improve the symptoms of patients with LDH. A selective, sensitive, and rapid ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of eight bioactive components in rat plasma. The plasma samples were extracted by simple protein precipitation with methanol. The protonated analytes were quantitated simultaneously in positive and negative ion modes by multiple reaction monitoring with a mass spectrometer. The calibration curve of eight components in plasma showed good linearity (r > .996) and the extraction recovery was 81.19% ± 2.15% - 100.39 ± 3.36 (relative standard deviation: 1.21%-10.70%). The accuracy of all the lower limit of quantitation values was quantified within 80%-120%, and the precision was less than 15%. This validated method was successfully applied to the pharmacokinetics study in rat plasma after ZQGC decoction oral treatment. Our research can provide experimental basis for the rational clinical application of ZQGC decoction in the treatment of LDH.

Duhuo jisheng decoction suppresses matrix degradation and apoptosis in human nucleus pulposus cells and ameliorates disc degeneration in a rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: The lower back pain (LBP) caused by intervertebral disc (IVD) degeneration brings a heavy burden to society. A classic treatment method of Chinese medicine, fangji-duhuo jisheng decoction (DHJSD), has been effective in the clinical treatment of LBP, although the underlying mechanism remains unknown. AIM OF THE STUDY: In this work, the main objective was to study the effects of DHJSD on in vitro IVD degeneration of human nucleus pulposus (NP) cells after pressure treatment and on an in vivo interrupted IVD degeneration rat model. MATERIALS AND METHODS: The effects of DHJSD on the viability of NP cells were detected using Cell Counting Kit-8. RT-qPCR, western blotting, TUNEL assay, transmission electron microscopy, and immunofluorescence staining were performed to explore the molecular mechanism underlying protection against compression-induced matrix degradation and apoptosis in NP cells by DHJSD. Furthermore, the effects of DHJSD on IVD degeneration in a rat IDD model were also determined. RESULTS: We found that DHJSD increased the viability of NP cells in a concentration- and time-dependent manner. Furthermore, DHJSD significantly reduced compression-induced NP matrix degeneration and apoptosis, activated autophagy, and inhibited the p38/MAPK signaling pathway in NP cells subjected to compression. Autophagy inhibitor 3-MA and p38/MAPK signaling pathway activator anisomycin reversed the beneficial effects of DHJSD in NP cells, indicating that DHJSD protects against IVD degeneration by autophagy activation and P38/MAPK signaling pathway inhibition. Furthermore, DHJSD treatment effectively delayed IVD degeneration in a puncture-induced IDD rat model. CONCLUSIONS: DHJSD prevents compression-induced matrix degradation and cell apoptosis through regulating autophagy and the P38/MAPK signaling pathway. The mechanism underlying the effects of DHSJD elucidated in this study provides a new direction for LBP treatment.

Efficiency of pulsed electromagnetic fields on pain, disability, anxiety, depression, and quality of life in patients with cervical disc herniation: a randomized controlled study

Background/aim: In this study, it was aimed to investigate the effects ofpulsed electromagnetic field(PEMF) therapy on pain, disability, psychological state, and quality of life in cervical disc herniation. Materials and methods: Patients were randomly divided into two groups, including Group 1, which received a therapy consisting of transcutaneous electrical nerve stimulation (TENS), hot pack (HP), and PEMF, and Group 2, which received a magnetic field (sham magnetic field) without current flow in addition to TENS and HP therapy. Pain was assessed by a visual analog scale (VAS, 0­10 cm). The other outcome measures were function (Neck Pain and Disability Scale), anxiety-depressive mood (Hospital Anxiety and Depression Scale), and quality of life (Nottingham Health Profile). All evaluations were performed at baseline, in the 3rd week, and in the 12th week after treatment. Results: A significant improvement was found in the neck pain, disability, depression, anxiety, and quality of life scores of both groups after treatment when compared to those before treatment. However, in the comparison between changes within groups, significant improvements were determined only in the VAS and Nottingham Health Profile sleep subparameter in the 12th week after treatment compared to those before treatment. Conclusion: PEMF therapy in cervical disc herniation can be used safely in routine treatment in addition to conventional physical therapy modalities.

Assessment of Changes in Lipids Metabolism in Patients with Degenerative Joints and Discs Diseases Subjected to Spa Therapy.

INTRODUCTION: High levels of total cholesterol, triglycerides, and, connected with them, lipoprotein fractions may result in atherosclerosis. There are various forms of therapy used to prevent cardiovascular diseases, such as balneophysiotherapy, the effectiveness of which is confirmed by numerous scientific publications. OBJECTIVE: The objective of this study was to assess the impact of balneophysiotherapeutic procedures on the systemic metabolism of lipids in patients suffering from osteoarthritis of the motor organ. MATERIAL AND METHODS: The study was conducted in the Health Resort Swieradów-Zdrój. Observation included patients undergoing radon water therapy. Before therapy and after 21 days of treatment, lipid profile was assessed with the use of standard colorimetric assay. Study group consisted of n=34 patients with degenerative joints and disc disease. The mean age of patients was 56.5l. The control group consisted of 17 people selected among the employees of the spa also suffering from osteoarthritis. The mean age was 54.2 years. RESULTS: The results of the study are based on a single, 21-day health resort stay period in April/May. A statistically significant increase in HDL cholesterol levels was observed in female patients having undergone health resort treatment (P<0.01). Statistically significant drops in LDL cholesterol and TG levels were observed in the control group (P<0.01). An increase in HDL levels was observed in the male and female control subjects, with P<0.05. CONCLUSIONS: (1) After the end of therapy, there were no changes in lipid metabolism in men, while in the group of women an increase in HDL level was observed. (2) In the control group, statistically significant changes in the field of lipid metabolism may be related to lifestyle changes as a result of educational activities conducted prior to the research. (3) Due to the divergent results, it is advisable to conduct randomized studies in a larger population. This trial is registered with NCT03274128.

Effect of Tai Chi Chuan on degeneration of lumbar vertebrae and lumbar discs in middle-aged and aged people: a cross-sectional study based on magnetic resonance images.

Objective Exercise has a positive effect on physical fitness. Tai Chi Chuan is a traditional Chinese aerobic exercise. We assessed the effect of Tai Chi on the degeneration of lumbar vertebrae and lumbar discs with magnetic resonance images. Methods This retrospective cohort study involved 2 groups of participants: 27 Tai Chi practitioners with more than 4 years of experience with regular Tai Chi exercise and 24 sex- and age-matched participants without Tai Chi experience. The lumbar magnetic resonance images of all participants were collected. The numbers of degenerated lumbar vertebrae and lumbar discs were evaluated by the same radiologist, who was blind to the grouping. Results The Tai Chi practitioners had significantly fewer degenerated lumbar vertebrae (1.9) and lumbar discs (2.3) than the control group (2.6 and 2.9, respectively). The most severely affected lumbar vertebrae and discs were L5 and L4/L5, respectively. Conclusion Regular performance of the simplified Tai Chi 24 form could possibly retard the degeneration of lumbar vertebrae and lumbar discs in middle-aged and aged people.

Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study.

BACKGROUND: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP. METHODS: We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 107 cells/disc (n = 5) or 4 × 107 cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year. RESULTS: No patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI. CONCLUSIONS: Combined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02338271 . Registered 7 January 2015.

Beyond the Laboratory, Into the Clinic: What Dogs with Disk Disease Have Taught Us About Photobiomodulation for Spinal Cord Injury.

BACKGROUND: For spinal-cord-injured (SCI) patients, integrative medicine approaches such as photomedicine and acupuncture can renew hope and offer previously unrecognized ways to help regain function and improve quality of life. OBJECTIVE: By understanding the mechanisms of action that these two modalities share, practitioners can better target specific attributes of spinal cord pathophysiology that are limiting recovery. Naturally occurring intervertebral disk disease (IVDD) in dogs affords unparalleled translational opportunities to develop treatment strategies involving photobiomodulation and acupuncture. CONCLUSIONS: Insights derived through clinical trials of dogs with IVDD have the potential to raise the standard of care for both human and canine SCI patients.

The influence of surface EMG-triggered multichannel electrical stimulation on sensomotoric recovery in patients with lumbar disc herniation: study protocol for a randomized controlled trial (RECO).

BACKGROUND: Intervertebral disc degeneration is one of the most common reasons for chronic low back pain and sensomotoric deficits, often treated by lumbar sequestrectomy. Nevertheless, the prognostic factors relevant for time and quality of recovery, of the surgical procedure, relative to conservative treatment, remain controversial and require further investigation. Surface electrical stimulation (SES) may be an influential intervention, already showing positive impact on motor and sensory recovery in different patient groups. Since mechanisms of SES still remain unclear, further inquiry is needed. METHODS/DESIGN: This is a prospective, monocentric, randomized, controlled clinical trial. A total of 80 adult patients suffering from a lumbar disc herniation (LDH; 40 treated surgically, 40 conservatively) are allocated in a ratio of 1:1. Patients in the treatment group will receive surface electromyography (EMG)-triggered electrical stimulation for eight weeks, whereas patients in the control group will not obtain any additional treatment. The primary outcome parameter is defined as the cold detection threshold (CDT), determined by quantitative sensory testing (QST), 24 months after intervention. Secondary outcome parameters include the inquiry of sensory nerve function by two-point discrimination and QST, the assessment of motor nerve function by manual muscle testing, and validated scales and scores. These include: the Oswestry Disability Index (ODI) and the Core Outcome Measures Index (COMI) assessing the domains pain, back-specific function, work disability, and patient satisfaction; the EQ-5D investigating the patient's generic health status; the painDETECT questionnaire (PD-Q) to identify neuropathic pain components; and the Beck Depression Inventory (BDI) to assess severity of depression. Moreover, neurological status, pain medication usage, and blood samples (CRP, TNFα, IL-1ß, IL-6) will be evaluated. Study data generation (study site) and data storage, processing, and statistical analysis are clearly separated. DISCUSSION: The results of the RECO study will detect the effect of EMG-triggered multichannel SES on the improvement of mechanical and thermal sensitivity and the effect on motor recovery and pain, associated with clinical and laboratory parameters. Furthermore, data comparing surgical and conservative treatment can be collected. This will hopefully allow treatment recommendations for patients with LDH accompanied by a sensomotoric deficit. TRIAL REGISTRATION: ISRCTN, ISRCTN12741173 . Registered on 15 January 2017.

Effects of Artcure Diffusional Patch application on pain and functional status in lumbar disc herniation patients: a prospective randomized controlled study.

BACKGROUND/AIM: The aim of this study was to assess the efficacy of the Artcure Diffusional Patch, which contains a mixture of 6 herbal oils (oleum thymi, oleum limonis, oleum nigra, oleum rosmarini, oleum chamomilla, oleum lauriexpressum) and has a hypoosmolar lipid structure, in the conservative treatment of lumbar disc herniation patients and to show the advantages and/or possibility of using this as an alternative method to surgery. MATERIALS AND METHODS: Of the 120 patients enrolled, 79 clinically diagnosed patients were included in the study. Clinical evaluations were performed on patients who had findings of protrusion or extrusion in their magnetic resonance results. The treatment group was treated with the Artcure Diffusional Patch while the control group received a placebo transdermal diffusional patch. The functional state of patients was measured using the Oswestry Disability Index and pain intensity was measured with a visual analog scale as primary outcomes. Secondary outcomes of the study were Lasegue's sign, the femoral stretching test, and paravertebral muscle spasm. RESULTS: The treatment group showed a dramatic recovery in the first month following the application in regards to Oswestry Disability Index scores and visual analog scale values. The patients treated with the Artcure Diffusional Patch showed a statistically significant difference in recovery as compared to the control group. CONCLUSION: These findings suggest that the Artcure Diffusional Patch may be an alternative for the conservative treatment of lumbar disc herniation with radiculopathy.

Effects of Bee Venom Injections at Acupoints on Neurologic Dysfunction Induced by Thoracolumbar Intervertebral Disc Disorders in Canines: A Randomized, Controlled Prospective Study.

Intervertebral disk disease (IVDD) is a major spine disorder in canines that causes neurological dysfunction, particularly in the thoracolumbar area. Analgesic and anti-inflammatory drugs are typically used to reduce nociceptive signals to decrease canine suffering. Bee venom (BV) has been reported to exert anti-inflammatory and analgesic effects. Injection of BV at acupoints has been widely used to treat clinical disorders including inflammation, pain, and arthritis. The current study was intended to determine whether BV injections at acupoints can enhance treatment of canine neurological dysfunction caused by IVDD. A single-blind controlled trial involving 40 adult canines with neurological dysfunction induced by IVDD subdivided into 2 groups was designed, and 36 canines finished the study. The myelopathy scoring system (MSS) grade and functional numeric scale (FNS) scores improved further after BV treatment than after control treatment. BV injection exerted a particularly strong effect on canines with moderate to severe IVDD and dramatically reduced clinical rehabilitation time. The results indicate that BV injections at acupoints are more effective at protecting canines from IVDD-induced neurological dysfunction and pain than is treatment alone.

Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats.

UNLABELLED: We investigated the effect of calcitonin (CT) on lumbar intervertebral disk degeneration (LIDD) in rats with ovariectomy-induced osteopenia. CT protected ovariectomized rats from LIDD by, at least in part, modifying extracellular matrix metabolism of the disks and preserving the microarchitecture and biomechanical properties of adjacent vertebrae. INTRODUCTION: The present study aimed to investigate the effect of CT on lumbar vertebral bone mineral density and intervertebral disk degeneration in ovariectomized (OVX) rats. METHODS: We first subjected 50 3-month-old female rats to either OVX (n = 30) or sham (n = 20). Twelve weeks later, ten OVX and ten sham rats were necropsied. The remaining OVX rats began to receive either saline vehicle (OVX + V, n = 10), or salmon CT (OVX + CT, 16 IU/kg/2 days, n = 10). After 12 weeks of treatment, necropsy was conducted and bone mineral density was determined in L3-4 and L5-6 vertebrae. The microstructure and biomechanical properties of L3 vertebrae were detected by micro-computed tomography and compression test, respectively. L5-6 was also used to measure intervertebral disk height and observe intervertebral disk histological changes by Van Gieson staining and histological scores, as well as immunohistochemistry (IHC) analysis of matrix metalloprotease (MMP)-1, MMP-13, and collagen II expression. RESULTS: At 12 weeks post-OVX, OVX rats had lower BV/TV and Tb.N and higher intervertebral disk histological score than sham rats. After 24 weeks, OVX + CT rats had higher BMD, BV/TV, Tb.N, and bone biomechanical strength values than OVX + V rats. Histological analysis showed OVX + CT rats had significantly lower disk degeneration scores than OVX + V rats. IHC analysis revealed CT treatment decreased expression of MMP-1 and MMP-13 and increased expression of collagen II compared with OVX + V rats. CONCLUSIONS: Our data demonstrate that CT-treated OVX rats display less intervertebral disk degeneration and favorable changes in intervertebral disk metabolism, associated with higher trabecular bone mass, better trabecular microarchitecture, and better biomechanical strength when compared to vehicle-treated OVX rats.

Do in vivo kinematic studies provide insight into adjacent segment degeneration? A qualitative systematic literature review.

PURPOSE: While much evidence suggests that adjacent segment degeneration is merely a manifestation of the natural degenerative process unrelated to any spine fusion, a significant body of literature supports the notion that it is a process due in part to the altered biomechanics adjacent to fused spine segments. The purpose of this study was to review and critically analyze the published literature that investigated the in vivo kinematics of the adjacent segments and entire lumbar spine in patients receiving spinal fusion or motion-preserving devices. METHODS: A systematic review of the PubMed database was conducted, initially identifying 697 studies of which 39 addressed the in vivo kinematics of the segments adjacent to spinal implants or non-instrumented fusion of the lumbar spine. RESULTS: Twenty-nine articles studied fusion, of which three reported a decrease in range of motion of the caudal adjacent segment post-fusion. Examining the rostral adjacent segment, twelve studies observed no change, nine studies found a significant increase, and three studies reported a significant decrease in sagittal plane range of motion. Of the six studies that analyzed motion for the entire lumbar spine as a unit, five studies showed a significant decrease and one study reported no change in global lumbar spine motion. Kinematics of the segment rostral to a total disc replacement was investigated in six studies: four found no change and the results for the other two showed dependence on treatment level. Fifteen studies of non-fusion posterior implants analyzed the motion of the adjacent segment with two studies noting an increase in motion at the rostral level. CONCLUSIONS: There appears to be no overall kinematic changes at the rostral or caudal levels adjacent to a fusion, but some patients (~20-30%) develop excessive kinematic changes (i.e., instability) at the rostral adjacent level. The overall lumbar ROM after fusion appears to decrease after a spinal fusion.

Hyperbaric oxygen treatment suppresses MAPK signaling and mitochondrial apoptotic pathway in degenerated human intervertebral disc cells.

Nucleus pulposus cells (NPCs) from degenerating discs produce catabolic and inflammatory factors, including interleukin (IL)-1 and nitric oxide (NO). Enhanced production of NO has been implicated in the apoptosis of degenerating disc cells. This study evaluates the effects of hyperbaric oxygen (HBO) on degenerated human NPCs. All hyperoxic cells were exposed to 100% O(2) at 2.5 atmospheres absolute (ATA). Phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in NPCs was detected using the phosphor-kinase array kit. RNA was isolated for real-time polymerase chain reaction (PCR) analysis of aggrecan and type II collagen gene expression. The levels of IL- 1ß and NO were quantified by enzyme-linked immunosorbent assay (ELISA). To identify the HBO-induced anti-apoptotic pathways, expression of Bcl-2 and Bax proteins as well as activation of cysteine-containing aspartate-specific proteases (caspases) 3, 8, and 9 was evaluated using Western blotting after HBO treatment. Our data showed that HBO treatment decreased the expression of IL-1ß, suppressed phosphorylation of ERK1/2, JNK, and p38 MAPK, decreased synthesis of NO, and increased the gene expression of aggrecan and type II collagen in NPCs as compared with the atmospheric treatment. HBO up-regulated the ratio of Bcl-2 to Bax expression and reduced the activity of caspases 9 and 3 but not of caspase 8, indicating a selective effect over the mitochondrial apoptosis pathway in degenerated NPCs. These results support our hypothesis that HBO treatment suppresses MAPK signaling and mitochondrial apoptotic pathway in degenerated human intervertebral disc cells.

Understanding the native nucleus pulposus cell phenotype has important implications for intervertebral disc regeneration strategies.

Low back pain is a leading cause of morbidity in developed societies and is strongly linked to degeneration of the intervertebral disc. The central nucleus pulposus (NP) region is most severely affected during disc degeneration and, consequently, is a focus for novel cell-based regenerative strategies. However, in order to develop such techniques, it is essential to first understand the biology and phenotype of the NP cells intended for repair. Microarray studies have highlighted novel NP markers that will allow a more accurate identification of cells for implantation, and along with other studies, have also revealed the potential importance of a developmental or immature NP cell phenotype in disseminating the optimal cell type for use. Additionally, the degenerative intervertebral disc is a harsh native environment and the effects of this on cells intended for implantation have yet to be fully elucidated; this is crucial for clinical translation of tissue engineered cell-based therapies.

Emerging trends in biological therapy for intervertebral disc degeneration.

Intervertebral disc disease is characterized by a series of deleterious changes in cellularity that lead to loss of extracellular matrix structure, altered biomechanical loading, and symptomatic pain. At present the "gold standard" of therapy is discectomy -- surgical removal of the diseased disc followed by fusion of the adjacent vertebral bodies. The procedure alleviates pain, but fusion limits range of motion and alters the mechanical loading at other spinal levels, hastening disease at previously unaffected sites. Biological therapeutics have the potential to repair damaged tissue by several means: (1) altering cell phenotype to regenerate matrix components, (2) augmenting tissue with reparative cells, (3) delivering bioactive materials to reestablish disc biomechanics and serve as a template for cell-based regeneration. Although research into biological treatments for disc degeneration has been ongoing for over a decade, few treatments have progressed to clinical testing and none are currently commercially available, primarily due to a limited understanding of disease etiology. Further work is needed to identify targets and interventional time points as disc degeneration progresses from early to later stages. This review focuses on emerging trends in biological treatments and identifies key obstacles to their clinical translation.