Treatment Of Discogenic Back Pain Research Articles

Engineered extracellular vesicle-based gene therapy for the treatment of discogenic back pain

Painful musculoskeletal disorders such as intervertebral disc (IVD) degeneration associated with chronic low back pain (termed “Discogenic back pain”, DBP), are a significant socio-economic burden worldwide and contribute to the growing opioid crisis. Yet there are very few if any successful interventions that can restore the tissue's structure and function while also addressing the symptomatic pain. Here we have developed a novel non-viral gene therapy, using engineered extracellular vesicles (eEVs) to deliver the developmental transcription factor FOXF1 to the degenerated IVD in an in vivo model. Injured IVDs treated with eEVs loaded with FOXF1 demonstrated robust sex-specific reductions in pain behaviors compared to control groups. Furthermore, significant restoration of IVD structure and function in animals treated with FOXF1 eEVs were observed, with significant increases in disc height, tissue hydration, proteoglycan content, and mechanical properties. This is the first study to successfully restore tissue function while modulating pain behaviors in an animal model of DBP using eEV-based non-viral delivery of transcription factor genes. Such a strategy can be readily translated to other painful musculoskeletal disorders.

Review: Discogenic Back Pain: Update on Treatment.

Lower back pain (LBP) has a lifetime prevalence of 80% in the United States population. Discogenic back pain (DBP), a subcategory of LBP, occurs as a result of the interverbal disc degeneration without disc herniation. Diagnosis relies on history, physical exam, and imaging such as MRI, provocative discography, or CT discography. Treatment of DBP involves a multifaceted approach with an emphasis on conservative measures including behavioral modification, pharmacologic management, and other non-pharmacologic interventions with invasive therapy reserved for select patients. Due to the paucity of data on the treatment of DBP, treatment also relies on data derived from treatment of chronic LBP (CLBP). Despite the scarcity of data for the treatment of DBP, treatments do exist with varying efficacy for DBP. Novel techniques such as the use of biologics may provide another avenue for treatment though further studies are needed to better evaluate the most efficacious regimen for both novel and existing treatments.

Netrin-1 mediates nerve innervation and angiogenesis leading to discogenic pain.

Discogenic low back pain (LBP) is associated with nociceptive nerve fibers that grow into degenerated intervertebral discs (IVD) but the etiopathogenesis of disease is not fully understood. The purpose of this study was to clarify the role of Netrin-1 in causing discogenic LBP. The level of nociceptive nerve innervation was examined in disc degenerative patients and rat needle-punctured models by immunohistochemistry. Nucleus pulposus (NP) cells were isolated from IVD tissues of rats and induced degeneration by interleukin-1β (IL-1β) or tumor necrosis factor α (TNFα). The candidate genes related to neuron outgrowth and migration were selected by Next-generation sequencing (NGS). CRISPR/Cas9 was used to knockdown Netrin-1 in NP cells. The impact of Netrin-1 on nerve innervation were evaluated with P2X2、NF200 staining and microfluidics assay. Meanwhile the CD31 staining and transwell assay were used to evaluate the impact of Netrin-1 in angiogenesis. The proteins and RNA extracted from NP cells related to catabolism and anabolism were examined by western blot assay and RT-qPCR experiment. ChIP and luciferase experiments were used to assess the intracellular transcriptional regulation of Netrin-1. Further, a needle-punctured rat model followed by histomorphometry and immunofluorescence histochemistry was used to explore the potential effect of Netrin-1 on LBP in vivo. The level of nerve innervation was increased in severe disc degenerative patients while the expression of Netrin-1 was upregulated. The supernatants of NP cells stimulated with IL-1β or TNFα containing more Netrin-1 could promote axon growth and vascular endothelial cells migration. Knocking down Netrin-1 or overexpressing transcription factor TCF3 as a negative regulator of Netrin-1 attenuated this effect. The needle-punctured rat model brought significant spinal hypersensitivity, nerve innervation and angiogenesis, nevertheless knocking down Netrin-1 effectively prevented disc degeneration-induced adverse impacts. Discogenic LBP was induced by Netrin-1, which mediated nerve innervation and angiogenesis in disc degeneration. Knocking down Netrin-1 by CRISPR/Cas9 or negatively regulating Netrin1 by transcription factor TCF3 could alleviate spinal hypersensitivity. This study on Netrin-1 could provide a new target and theoretical basis for the prevention and treatment for discogenic back pain.

Alleviating Paravertebral Muscle Spasm after Radiofrequency Ablation Treatment of Hypersensitive Basivertebral and Sinuvertebral Nerves for Chronic Discogenic Back Pain

Paraspinal muscle spasm caused by pain from a lumbar degenerative disc is frequently investigated in patients with low back pain. Radiofrequency ablation (RFA) surgery could alleviate paraspinal muscle spasms. We performed RFA surgery on the high-intensity zone (HIZ) and hypersensitive sinuvertebral and basivertebral nerves to evaluate its outcome. The paravertebral muscle cross-sectional area (CSA) was measured on magnetic resonance imaging (MRI) before and after surgery to evaluate the effect of RFA surgery on the paravertebral muscle. Prospective cohort study. A single spine surgery center. A comparative study was performed on 2 different uniportal spinal endoscopic surgery groups; 23 patients who underwent RFA surgery for chronic discogenic back pain and 45 patients who underwent posterior decompression surgery for lumbar spinal stenosis with 12 months of follow-up. Paravertebral muscle cross-sectional area, Schiza grade, Modic type, and HIZ size were measured on pre- and post-operative MRI. An endoscopic video review was performed to evaluate the presence of intraoperative twitching and grade the degree of epidural neovascularization and adhesion. Visual analog scale VAS, modified Oswestry Disability Index, ODI and MacNab's criteria were evaluated for outcome measures. Intraoperative endoscopic video evaluation showed neovascularization and adhesion adjacent to the disc and pedicle. In the RFA surgery group, there were 7 patients (30.43%) with grade 2 and 16 (69.57%) with grade 3 neovascularization; intraoperative twitching was observed in 19 out of 23 patients (82.61%). After performing an RFA on the sinuvertebral and basivertebral nerves for the treatment of discogenic back pain, the results showed significant improvement in pain and disability scores. The mean CSA of the paraspinal muscle in the RFA surgery group was significantly increased after surgery at the L4-L5 and L5-S1 levels (L4-L5: 3901 ± 1096.7 mm² to 4167 ± 1052.1 mm², P = 0.000; L5-S1: 3059 ± 968.5 mm² to 3323 ± 1046.2 mm², P = 0.000) compared to preoperative CSA. This study was limited by its small sample size. Hypersensitive sinuvertebral and basivertebral nerves are strongly associated with epidural neovascularization with adhesion and the pathological pain pathway in degenerative disc disease. Epidural neovascularization with adhesion reflects aberrant neurological connections, which are associated with reflex inhibitory mechanisms of the multifidus muscle, which induces spasm. RFA treatment of the region of epidural neovascularization with adhesion effectively treated chronic discogenic back pain and could induce paraspinal muscle spasm release.

Risks of Intradiscal Orthobiologic Injections: A Review of the Literature and Case Series Presentation.

Intervertebral disc disease (IDD) is responsible for a large portion of back pain with historically suboptimal treatments for long-term improvement. IDD pathogenesis is thought to arise at a cellular and biochemical level, making biologically based injections an area of clinical interest. Although human studies have shown promise, emerging data suggest there may be risks inherent to such injections that were previously unrecognized. The aim of this review is to summarize the known risks to date and provide mitigation steps to reduce potential complications in the future. In addition, we present a small case series of serious adverse events (SAEs) from our clinical practice. A literature review was performed to identify human intradiscal autologous biologic injection studies to date, including mesenchymal signaling cells (MSCs) and platelet-rich plasma (PRP) preparations, which were reviewed for complications. Cases of complication following intradiscal orthobiologic injection were identified from a single outpatient center and reviewed. Publications of MSC-based intradiscal injection documented 136 total patients treated with two SAEs reported, one infection and one progressive disc herniation. Publications of PRP intradiscal injection included 194 patients with one SAE reported. We also review three cases of previously unpublished SAEs, including one case of confirmed infection with Cutibacterium acnes (C acnes) and two presumed cases of discitis without pathogen confirmation. Bone marrow concentrate was the injectate in all three cases. Although biologic intradiscal injection shows promise for the treatment of discogenic back pain, there are inherent risks to be considered and mitigated. We currently recommend a leukocyte-rich PRP and a two-needle delivery technique coupled with intradiscal gentamicin to mitigate the risk of postinjection spondylodiscitis. Further research is needed using large registries to not only track clinical outcomes but also complication rates.

Efficacy and safety of nucleo-annuloplasty using radiofrequency ablation for discogenic back pain in a local Hong Kong population

Purpose: Degenerative disk disease is a global and common debilitating condition with substantial healthcare and economic costs. Disc-Fx is a relatively new minimally invasive, percutaneous nucleo-annuloplasty procedure aimed to alleviate symptoms of discogenic back pain via manual discectomy with nuclear and annular modification via means of radiofrequency ablation. The aim of this retrospective study is to report the 1-year outcomes, efficacy and safety of the percutaneous nucleo-annuloplasty procedure for treatment of discogenic back pain in the local Hong Kong population. Methods: This retrospective study consists of 16 patients with a total of 24 levels from 2017 to –2019 with at least 6 months of chronic back pain failing conservative management, MRI-confirmed disc degeneration, and who have undergone percutaneous nucleo-annuloplasty via Disc-Fx procedure. All patients had plain radiography and magnetic resonance imaging prior to procedure. Percutaneous nucleo-annuloplasty was only performed in patients with confirmed discogenic back pain via a positive provocative test on discography. Results: The mean functional outcome of Oswestry Disability Index improved from 46.25 points preoperatively to 24.12 at the of 1-year follow-up (p-value = 0.00). The Numerical Pain Rating Scale improved from 6.25 points to 4.4 points (p-value: 0.01) and 14.56 points to 8.85 points (p-value = 0.01) at preoperative to 1-year post-procedure respectively. There were no reported procedural related complications in the study population. Conclusion: The procedure of percutaneous nucleo-annuloplasty shows to be a relatively safe procedure that can be considered in patients with discogenic back pain. Larger studies would be desired to draw further conclusions about its efficacy.

Use of Pulsed Radiofrequency for the Treatment of Discogenic Back Pain: A Narrative Review.

Low-back pain (LBP) is one of the most frequently reported symptoms of patients who visit pain clinics, and a significant proportion of them have discogenic pain. Pulsed radiofrequency (PRF) stimulation is an effective treatment for various types of pain. We reviewed articles which investigated the effectiveness of intradiscal PRF for controlling discogenic LBP. We searched PubMed for papers published prior to August 7, 2020, in which intradiscal PRF was used for treating discogenic LBP. The key search phrase was (intradiscal PRF) for identifying potentially relevant articles. We included articles in which intradiscal PRF was used for controlling LBP. Review articles were excluded. Nine publications were included in this review. Except for one study, all other studies showed positive therapeutic outcomes after treating discogenic LBP using intradiscal PRF. However, the quality of these studies was not high. This review showed that intradiscal PRF appears to be a helpful treatment method for patients with discogenic LBP. Our review provides insights into the degree of evidence of the therapeutic effects of intradiscal PRF for alleviating discogenic LBP. For confirmation of the effectiveness of intradiscal PRF on discogenic LBP, more high-quality studies are necessary.

Degenerate intervertebral disc-like pH induces a catabolic mechanoresponse in human nucleus pulposus cells.

Mechanical stimulation is known to influence intervertebral disc (IVD) cell behavior and function, but the effect on disc cells is routinely considered in isolation from other microenvironmental factors. Acidic pH has been shown to be a prominent and detrimental microenvironmental factor present in degenerate IVDs, but its influence on the human disc cell mechanoresponse has never been studied. We investigated the response of agarose‐encapsulated human nucleus pulposus (NP) cells to 0.004 MPa, 1.0 Hz and 1 hour of compression (Flexcell FX4000 Compression System) under pH conditions representative of nondegenerate (pH 7.1) and degenerate (pH 6.5) IVDs. Cell viability, extracellular matrix production, and expression of anabolic/anti‐catabolic and catabolic genes were assessed. We report that preculture of NP cells in agarose gels was required in order for cells to be mechanoresponsive, and this correlated with increased type VI collagen, α5β1 integrin, and fibronectin expression. Furthermore, the matrix homeostatic response observed at pH 7.1 (representative of nondegenerate IVDs; increased aggrecan [AGC], tissue inhibitor of metalloproteinases‐1 [TIMP1], matrix metalloproteinase‐3 [MMP3], a disintegrin and metalloproteinase with thrombospondin motif‐5 [ADAMTS5] gene expression) was RGD‐integrin dependent, whereas only MMP3 remained mechanoresponsive at pH 6.5, and this was independent of RGD‐integrins. Our findings suggest differential mechanotransduction pathways operating for specific genes, with RGD‐integrin dependent AGC expression, but not RGD‐independent MMP3 expression, inhibited at pH representative of degenerate IVDs (pH 6.5), which could contribute to the catabolic phenotype observed during IVD degeneration.Clinical significanceCharacterizing the influence of the mechanical and chemical intervertebral disc microenvironment on disc cells, particularly in disc degeneration, could help develop future therapeutic strategies for the treatment of discogenic back pain.

Clinical and Radiological Mid-Term Outcomes of Lumbar Single-Level Total Disc Replacement

Prospective single-center case cohort study. Evaluation of clinical and radiographic outcomes of a consecutive 122-patient cohort with discogenic back pain, at 2- to 10-year follow-up periods, treated by a single surgeon, with CHARITÉ Artificial Disc (DePuy Spine, Raynham, MA). Minimum 2-year clinical and radiographic level 1 data for the first lumbar artificial disc, the CHARITÉ Artificial Disc (DePuy Spine), have recently been published, demonstrating sustained clinical benefit of the device for the treatment of degenerative disc disease. Patients were assessed preoperatively using clinical outcome measures, including visual analog scale (VAS) score back and leg, Oswestry Disability Index (ODI), 36-Item Short Form Health Survey (SF-36), and Roland-Morris Questionnaires (RMDQ), and further assessed postoperatively, 3-, 6-, 12-months, and yearly thereafter. Average follow-up was 44.9 ± 23.3 months (n = 122). The median age at surgery was 43.0 ± 9.0 years. Preoperative diagnosis included degenerative disc disease in 118 (96.7%) and internal disc disruption in 4 (3.3%). Surgery was performed at L5-S1 in 96 (77.9%) patients and at L4-L5 in 27 (22.1%). Statistically significant clinical improvements from baseline were observed on VAS (back and leg), ODI, SF-36 PCS, SF-36 MCS, and RMDQ 3 months onward. Back VAS scores decreased from 78.2 ± 21.3 preoperatively to 21.9 ± 27.8 by final follow-up. ODI scores decreased from 51.1 ± 17.3 to 16.2 ± 17.9 at last follow-up. The RMDQ scores also decreased from 16.7 ± 4.7 to 4.2 ± 5.8. SF-36 PCS and MCS increased from 25.7 ± 11.0 to 46.4 ± 10.3 for PCS and from 35.5 ± 17.4 to 51.6 ± 10.8 for MCS. Patient satisfaction surveys indicated that 90.56% patients rated their satisfaction with the surgery as "excellent" or "good" at 2 years. Range of motion averaged 8.6 ± 3.5 (median = 8.0°) at the last follow-up time point. Outcomes verify the clinical efficacy of total disc replacement for treatment of discogenic back pain with or without radiculopathy. The outcomes instruments demonstrated statistically significant improvements 3 months onward. N/A.

Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up.

The purpose of this study is to assess safety and feasibility of intradiscal bone marrow concentrate (BMC) injections to treat discogenic pain as an alternative to surgery. A total of 26 patients (11 male, 15 female, aged 18-61 years, 13 single level, 13 two level) that met inclusion criteria of chronic (> 6 months) discogenic low back pain, degenerative disc pathology assessed by magnetic resonance imaging (MRI) with modified Pfirrmann grade of IV-VII at one or two levels, candidate for surgical intervention (failed conservative treatment and radiologic findings) and a visual analogue scale (VAS) pain score of 40 mm or more at initial visit. Initial Oswestry Disability Index (ODI) and VAS pain score average was 56.5 % and 80.1 mm (0-100), respectively. Adverse event reporting, ODI score, VAS pain score, MRI radiographic changes, progression to surgery and cellular analysis of BMC were noted. Retrospective cell analysis by flow cytometry and colony forming unit-fibroblast (CFU-F) assays were performed to characterise each patient's BMC and compare with clinical outcomes. The BMC was injected into the nucleus pulposus of the symptomatic disc(s) under fluoroscopic guidance. Patients were evaluated clinically prior to treatment and at three, six, 12 and 24 months and radiographically prior to treatment and at 12 months. There were no complications from the percutaneous bone marrow aspiration or disc injection. Of 26 patients, 24 (92 %) avoided surgery through 12 months, while 21 (81 %) avoided surgery through two years. Of the 21 surviving patients, the average ODI and VAS scores were reduced to 19.9 and 27.0 at three months and sustained to 18.3 and 22.9 at 24 months, respectively (p ≤ 0.001). Twenty patients had follow-up MRI at 12 months, of whom eight had improved by at least one Pfirrmann grade, while none of the discs worsened. Total and rate of pain reduction were linked to mesenchymal stem cell concentration through 12 months. Only five of the 26 patients elected to undergo surgical intervention (fusion or artificial disc replacement) by the two year milestone. This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC, with durable pain relief (71 % VAS reduction) and ODI improvements (> 64 %) through two years.

Can intractable discogenic back pain be managed by low-level laser therapy without recourse to operative intervention?

ObjectiveThe aim of the study reported here was to investigate the possible clinical role of low-level laser therapy (LLLT) in discogenic back pain patients who failed to respond to a conventional physical therapy program to avoid recourse to operative intervention.MethodsThe paper reports on the long-term mean 5-year prospective follow-up of a patient cohort of 50 unselected patients visiting our tertiary referral pain center for discogenic back pain who had had a single-level lesion documented by magnetic resonance imaging followed by subsequent discography to confirm the affected disc being the pain generator. All of the patients who entered the study had failed response to a combination of nonsteroidal anti-inflammatory agents and had had not less than 3 months of conventional physical therapy. LLLT, at a wavelength of 810 nm wavelength emitted from a GaAIAs semiconductor laser device with 5.4 J per point and a power density of 20 mW/cm2, was employed. The treatment regimen consisted of three sessions of treatment per week for 12 consecutive weeks.ResultsAll but one patient had significant improvement in their Oswestry Disability Index score, from a mean of 50% score to a mean of 10% score, at the end of treatment at 12 weeks. In addition, surprisingly, the improvement was found maintained at follow-up assessments 1 year and 5 years later. The one patient among the 50 patients who failed to respond eventually required surgery, while the others did not require surgery.ConclusionWe conclude that LLLT is a viable option in the conservative treatment of discogenic back pain, with a positive clinical result of more than 90% efficacy, not only in the short-term but also in the long-term, with lasting benefits.

Intact glycosaminoglycans from intervertebral disc-derived notochordal cell-conditioned media inhibit neurite growth while maintaining neuronal cell viability

Background contextPainful human intervertebral discs (IVDs) exhibit nerve growth deep into the IVD. Current treatments for discogenic back pain do not address the underlying mechanisms propagating pain and are often highly invasive or only offer temporary symptom relief. The notochord produces factors during development that pattern the spine and inhibit the growth of dorsal root ganglion (DRG) axons into the IVD. We hypothesize that notochordal cell (NC)-conditioned medium (NCCM) includes soluble factors capable of inhibiting neurite growth and may represent a future therapeutic target. PurposeTo test if NCCM can inhibit neurite growth and determine if NC-derived glycosaminoglycans (GAGs) are necessary candidates for this inhibition. Study designHuman neuroblastoma (SH-SY5Y) cells and rat DRG cells were treated with NCCM in two-dimensional culture in vitro, and digestion and mechanistic studies determined if specific GAGs were responsible for inhibitory effects. MethodsNotochordal cell-conditioned medium was generated from porcine nucleus pulposus tissue that was cultured in Dulbecco's modified eagle's medium for 4 days. A dose study was performed using SH-SY5Y cells that were seeded in basal medium for 24 hours and neurite outgrowth and cell viability were assessed after treatment with basal media or NCCM (10% and 100%) for 48 hours. Glycosaminoglycans from NCCM were characterized using multiple digestions and liquid chromatography mass spectroscopy (LC-MS). Neurite growth was assessed on both SH-SY5Y and DRG cells after treatment with NCCM with and without GAG digestion. ResultsNotochordal cell-conditioned medium significantly inhibited the neurite outgrowth from SH-SY5Y cells compared with basal controls without dose or cytotoxic effects; % of neurite expressing cells were 39.0±2.9%, 27.3±3.6%, and 30.2±2.7% and mean neurite length was 60.3±3.5, 50.8±2.4, 53.2±3.7 μm for basal, 10% NCCM, and 100% NCCM, respectively. Digestions and LC-MS determined that chondroitin-6-sulfate was the major GAG chain in NCCM. Neurite growth from SH-SY5Y and DRG cells was not inhibited when cells were treated with NCCM with digested chondroitin sulfate (CS). ConclusionsSoluble factors derived from NCCM were capable of inhibiting neurite outgrowth in multiple neural cell types without any negative effects on cell viability. Cleavage of GAGs via digestion was necessary to reverse the neurite inhibition capacity of NCCM. We conclude that intact GAGs such as CS secreted from NCs are potential candidates that could be useful to reduce neurite growth in painful IVDs.

Elevated VEGF in Degenerative Intervertebral Discs in Rats with Injured Intervertebral Discs of the Caudal Vertebrae

Introduction Recently, inflammatory cytokines, which are elevated in degenerative intervertebral discs, have been recognized as targets of drug therapy for discogenic back pain. Some reports have shown that the level of vascular endothelial growth factor (VEGF), a protein involved in angiogenesis, is elevated at inflamed sites, and we believed that VEGF could be a target for the treatment of discogenic back pain. Thus, we investigated the presence of VEGF in degenerative intervertebral discs in rats with injured intervertebral discs of the caudal vertebrae. Materials and Methods Forty male rats (age, 8 weeks) were divided into two groups: injured group (intervertebral discs between the fifth and sixth, and sixth and seventh caudal vertebrae were punctured 10 times using a 26G needle) and noninjured group (intact discs). The intervertebral discs were collected at 1, 4, 7, and 14 days after the procedure ( n = 5 from each group at each time point), and quantitative evaluation of VEGF was performed using ELISA. Results The VEGF level was maximum 1 day after the procedure, and then the level gradually decreased. In addition, the VEGF levels during the entire study period were significantly higher in the injured group compared with those in the noninjured group ( p < 0.05). Conclusion In this study, injury to the intervertebral discs resulted in elevated VEGF levels. This finding confirms the increased production of inflammatory cytokines in injured intervertebral discs and indicates that VEGF might be involved in discogenic back pain. Moreover, the presence of elevated VEGF levels during the study period shows that VEGF might be responsible for lingering pain. Anti-VEGF antibodies are already in use in the ophthalmic field. On the basis of the findings in this study, a clinical trial involving the administration of anti-VEGF antibodies into the intervertebral discs for the treatment of low back pain in humans was approved by the review committee in September 2013 and will be performed in the near future. Disclosure of Interest None declared

One-year outcomes of surgical versus nonsurgical treatments for discogenic back pain: a community-based prospective cohort study

Background contextThe clinical entity “discogenic back pain” remains controversial at fundamental levels, including its pathophysiology, diagnostic criteria, and optimal treatment. This is true despite availability of four randomized trials comparing the efficacy of surgical and nonsurgical treatments. One trial showed benefit for lumbar fusion compared with unstructured nonoperative care, and three others showed roughly similar results for lumbar surgery and structured rehabilitation. PurposeTo compare outcomes of community-based surgical and nonsurgical treatments for patients with chronic back pain attributed to degeneration at one or two lumbar disc levels. DesignProspective observational cohort study. Patient samplePatients presenting with axial back pain to academic and private practice orthopedic surgeons and neurosurgeons in a large metropolitan area. Outcome measuresRoland-Morris back disability score (primary outcome), current rating of overall pain severity on a numerical scale, back and leg pain bothersomeness measures, the physical function scale of the short-form 36 version 2 questionnaire, use of medications for pain, work status, emergency department visits, hospitalizations, and further surgery. MethodsPatients receiving spine surgery within 6 months of enrollment were designated as the “surgical treatment” group and the remainder as “nonsurgical treatment.” Outcomes were assessed at 3, 6, 9, and 12 months after enrollment. ResultsWe enrolled 495 patients with discogenic back pain presenting for initial surgical consultation in offices of 16 surgeons. Eighty-six patients (17%) had surgery within 6 months of enrollment. Surgery consisted of instrumented fusion (79%), disc replacement (12%), laminectomy, or discectomy (9%). Surgical patients reported more severe pain and physical disability at baseline and were more likely to have had prior surgery. Adjusting for baseline differences among groups, surgery showed a limited benefit over nonsurgical treatment of 5.4 points on the modified (23-point) Roland disability questionnaire (primary outcome) 1 year after enrollment. Using a composite definition of success incorporating 30% improvement in the Roland score, 30% improvement in pain, no opioid pain medication use, and working (if relevant), the 1-year success rate was 33% for surgery and 15% for nonsurgical treatment. The rate of reoperation was 11% in the surgical group; the rate of surgery after treatment designation in the nonsurgical group was 6% at 12 months after enrollment. ConclusionsThe surgical group showed greater improvement at 1 year compared with the nonsurgical group, although the composite success rate for both treatment groups was only fair. The results should be interpreted cautiously because outcomes are short term, and treatment was not randomly assigned. Only 5% of nonsurgical patients received cognitive behavior therapy. Nonsurgical treatment that patients received was variable and mostly not compliant with major guidelines.

Delayed hypersensitivity reaction caused by metal-on-metal total disc replacement

The authors report the case of a 53-year-old woman who underwent placement of a metal-on-metal total disc replacement (TDR) device for the treatment of discogenic back pain. The initial postoperative course was normal, but 2 months after surgery she started to complain of a recurrence of pain and she progressively developed cauda equina syndrome. Radiological and biological findings showed an inflammatory polyneuropathy associated with an epidural mass. A diagnosis of cell-mediated hypersensitivity reaction (Type IV) was made after patch testing showed positive reactions for 1% cobalt chloride and chromium. A decision was made to remove the TDR device and to perform a circumferential fusion. This report is intended to inform the reader that systemic metal release and hypersensitivity reaction are possible complications of metal-on-metal TDR.

Diagnostic Discography: What is the Clinical Utility?

The diagnosis and treatment of discogenic back pain is challenging. Provocation discography, an invasive spinal procedure, has been suggested as a diagnostic test for internal disc disruption to provide information on disc morphology and reproduction of symptoms. Current applications consist of the evaluation of persistent spinal pain in individuals, including postoperative patients, as well as providing a guide for patient selection for spinal fusion surgery and minimally invasive interventional pain procedures. While the validity of discography has been questioned by multiple scientific studies, technical refinements have addressed many of the initial limitations. An updated review on the safety and utility of discography will be provided, covering key areas of debate including false-positive rates, technical parameters, clinical utility, and risk of discography procedural-related intervertebral disc damage.

Nanoparticle Formulation for Controlled Release of Capsaicin

Capsaicin might be an effective pharmacological agent for the treatment of discogenic back pain due to its effect on pain control neuronal degeneration. Therefore, capsaicin-loaded nano- and micro-particles for sustained release were formulated by nano-precipitation or oil-in-water single emulsion solvent evaporation/extraction method. First, the capsaicin-loaded PLGA nanoparticles were prepared by nano-precipitation method. By increasing the volume of oil-water ratio from 1:2 to 1:5, slight changes in size from 162 +/- 3 nm to 153 +/- 3 nm and in drug loading efficiency from 25% to 20% were observed, whereas the drug release period was significantly changed from 11 days for 1:2 to 5 days for 1:5 ratio. To get a more sustained release, a modified single emulsion method was applied with three kinds of biocompatible polymers (PLLA, PLGA, and PCL). Among them, PLLA particles showed a much sustained release profile than PLGA or PCL ones with the similar size. For PLLA particles, particles size and drug encapsulation efficiency increased as the oil/water ratio decreased, and the bigger particles showed the slower release profiles as well as the higher drug-loading efficiency, thus about 1 month release was obtained with 800 nm particles. In conclusion, formulation for the controlled release of capsaicin from 1 week to 1 month was prepared by using biocompatible nanoparticles.

Controversy surrounds new treatment for discogenic back pain

My back hurts Doc. It’s one of the most common complaints heard by family doctors. Various estimates have suggested that 80% of people will experience at least one episode of back pain over their lifetimes. Traditional treatments of discogenic back pain have ranged from conservative management

Investigation of the in-vitro loading on an artificial spinal disk prosthesis

Spinal diseases imposes considerable burden to both patients and society. In recent years, much surgical efforts have been made in advancing the treatment of neck and back pain. Of particular prominence is the increasing clinical acceptance and use of intervertebral artificial disk prosthesis for the treatment of discogenic back pain. Despite this increased use of such disks, their in-vivo monitoring remains rudimentary. In an effort to develop an intelligent artificial spinal disk where the in-vivo loading of the spine can by studied for the first time an experimental set up has been created in order to initially study the in-vitro loading on an artificial disc prosthesis. Eight strain gauges and two piezoresistive sensors were used and placed suitably in the artificial disk prosthesis. The results from the in-vitro loading showed linear relationship between loading and the outputs from the sensors with good repeatability and less hysteresis.

Management of Symptomatic Lumbar Degenerative Disk Disease

Symptomatic lumbar degenerative disk disease, or discogenic back pain, is difficult to treat. Patients often report transverse low back pain that radiates into the sacroiliac joints. Radicular or claudicatory symptoms are generally absent unless there is concomitant nerve compression. Physical examination findings are often unremarkable. Radiographic examination may reveal disk space narrowing, end-plate sclerosis, or vacuum phenomenon in the disk; magnetic resonance imaging is useful for revealing hydration of the disk, annular bulging, or lumbar spine end-plate (Modic) changes in the adjacent vertebral bodies. The use of diskography as a confirmatory study remains controversial. Recent prospective, randomized trials and meta-analyses of the literature have helped expand what is known about degenerative disk disease. In most patients with low back pain, symptoms resolve without surgical intervention; physical therapy and nonsteroidal anti-inflammatory drugs are the cornerstones of nonsurgical treatment. Intradiskal electrothermal treatment has not been shown to be effective, and arthrodesis remains controversial for the treatment of discogenic back pain. Nucleus replacement and motion-sparing technology are too new to have demonstrated long-term data regarding their efficacy.