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1.
Expert Opin Emerg Drugs ; 29(2): 155-164, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38602142

RESUMO

INTRODUCTION: Chronic lower back pain is a leading cause of disability and healthcare spending worldwide. Discogenic pain, pain originating from the intervertebral disk, is a common etiology of chronic lower back pain. Currently, accepted treatments for chronic discogenic pain focus only on the management of symptoms, such as pain. There are no approved treatments that stop or reverse degenerating intervertebral discs. Biologic therapies promoting disc regeneration have been developed to expand treatment options. VIADISC™ NP, is a viable disc allograft supplementation that, in a recent trial, demonstrated a significant reduction in pain and increased function in patients suffering from symptomatic degenerative disc disease. AREAS COVERED: This manuscript summarizes the epidemiology and etiology of low back pain, the pathophysiology of degenerative disc disease, current treatments, and a need for newer therapies. The rationale behind intradiscal biologics for the treatment of symptomatic degenerative disc disease is also discussed. EXPERT OPINION: Characterization of the biology leading to disc degeneration has allowed for the development of intradiscal biologics. They may soon be capable of preventing and reversing disc degeneration. Clinical trials have shown promise, but further research into efficacy and safety is needed before these therapies are widely employed.


Assuntos
Dor Crônica , Degeneração do Disco Intervertebral , Dor Lombar , Humanos , Degeneração do Disco Intervertebral/fisiopatologia , Dor Lombar/etiologia , Dor Lombar/fisiopatologia , Dor Lombar/tratamento farmacológico , Dor Lombar/terapia , Dor Crônica/tratamento farmacológico , Dor Crônica/fisiopatologia , Dor Crônica/etiologia , Animais , Disco Intervertebral/fisiopatologia , Disco Intervertebral/patologia , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/administração & dosagem , Desenvolvimento de Medicamentos
2.
J Nanobiotechnology ; 22(1): 486, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143545

RESUMO

Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration.


Assuntos
Autofagia , Degeneração do Disco Intervertebral , Nanopartículas , Ratos Sprague-Dawley , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Animais , Autofagia/efeitos dos fármacos , Nanopartículas/química , Ratos , Masculino , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Dor Lombar/tratamento farmacológico , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Sirolimo/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Núcleo Pulposo/metabolismo , Inflamação/tratamento farmacológico , Citocinas/metabolismo , Biomimética/métodos , Modelos Animais de Doenças , Fator de Crescimento Neural/metabolismo , Células RAW 264.7
3.
Curr Pain Headache Rep ; 28(8): 825-833, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38850492

RESUMO

PURPOSE OF REVIEW: The present investigation evaluates clinical uses and roles of platelet rich plasma in the management of vetrebrogenic and discogenic mediated pain states. RECENT FINDINGS: Back pain is a common and significant condition that affects millions of people around the world. The cause of back pain is often complex and multifactorial, with discogenic and vertebrogenic pain being two subtypes of back pain. Currently, there are numerous methods and modalities in which back pain is managed and treated such as physical therapy, electrical nerve stimulation, pharmacotherapies, and platelet-rich plasma. To conduct this systematic review, the authors used the keywords "platelet-rich plasma", "vertebrogenic pain", and "discogenic pain", on PubMed, EuroPMC, Who ICTRP, and clinicaltrials.gov to better elucidate the role of this treatment method for combating vertebrogenic and discogenic back pain. In recent decades, there has been a rise in popularity of the use of platelet-rich plasma for the treatment of numerous musculoskeletal conditions. Related to high concentration of platelets, growth factors, cytokines, and chemokines, platelet-rich plasma is effective in reducing pain related symptoms and in the treatment of back pain. Platelet-rich plasma use has evolved and gained popularity for pain related conditions, including vertebrogenic and discogenic back pain. Additional well-designed studies are warranted in the future to better determine best practice strategies to provide future clinicians with a solid foundation of evidence to make advancements with regenerative medical therapies such as platelet-rich plasma.


Assuntos
Plasma Rico em Plaquetas , Humanos , Dor nas Costas/terapia , Dor nas Costas/sangue
4.
Int J Mol Sci ; 25(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339040

RESUMO

Chronic painful intervertebral disc (IVD) degeneration (i.e., discogenic pain) is a major source of global disability needing improved knowledge on multiple-tissue interactions and how they progress in order improve treatment strategies. This study used an in vivo rat annulus fibrosus (AF) injury-driven discogenic pain model to investigate the acute and chronic changes in IVD degeneration and spinal inflammation, as well as sensitization, inflammation, and remodeling in dorsal root ganglion (DRG) and spinal cord (SC) dorsal horn. AF injury induced moderate IVD degeneration with acute and broad spinal inflammation that progressed to DRG to SC changes within days and weeks, respectively. Specifically, AF injury elevated macrophages in the spine (CD68) and DRGs (Iba1) that peaked at 3 days post-injury, and increased microglia (Iba1) in SC that peaked at 2 weeks post-injury. AF injury also triggered glial responses with elevated GFAP in DRGs and SC at least 8 weeks post-injury. Spinal CD68 and SC neuropeptide Substance P both remained elevated at 8 weeks, suggesting that slow and incomplete IVD healing provides a chronic source of inflammation with continued SC sensitization. We conclude that AF injury-driven IVD degeneration induces acute spinal, DRG, and SC inflammatory crosstalk with sustained glial responses in both DRGs and SC, leading to chronic SC sensitization and neural plasticity. The known association of these markers with neuropathic pain suggests that therapeutic strategies for discogenic pain need to target both spinal and nervous systems, with early strategies managing acute inflammatory processes, and late strategies targeting chronic IVD inflammation, SC sensitization, and remodeling.


Assuntos
Anel Fibroso , Dor Crônica , Degeneração do Disco Intervertebral , Disco Intervertebral , Ratos , Animais , Disco Intervertebral/lesões , Doenças Neuroinflamatórias , Gânglios Espinais , Degeneração do Disco Intervertebral/complicações , Dor Crônica/complicações , Medula Espinal
5.
Zh Vopr Neirokhir Im N N Burdenko ; 87(6): 106-113, 2023.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-38054234

RESUMO

Low back pain is one of the most common complaints in primary care. This pain is usually nonspecific and musculoskeletal. However, identification and exclusion of specific causes of pain as early as possible are important for specialists since their underestimation can sometimes lead to life-threatening consequences. The authors analyze literature data on the key facts of anamnesis («red flags¼), management of patients with low back pain with emphasis on modern concepts and recommendations for diagnostics, identifying the dominant nature and cause of pain, differential diagnosis, and diagnostic significance of neuroimaging. Special attention is paid to existing options for conservative (drug and non-drug therapy) and interventional treatment methods, which have become increasingly popular in recent years.


Assuntos
Dor Lombar , Humanos , Dor Lombar/terapia , Dor Lombar/cirurgia
6.
Int Orthop ; 46(6): 1381-1385, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35344055

RESUMO

PURPOSE: This study aimed to assess clinical outcomes following intradiscal injections of higher-concentration (> 10 ×) platelet-rich plasma (PRP) in patients with chronic lumbar discogenic pain and to compare outcomes with a historical cohort. METHODS: This retrospective study included 37 patients who received intradiscal injections of higher-concentration (> 10 ×) PRP and had post-procedure outcomes data (visual numerical scale pain score, Functional Rating Index [FRI], and NASS Patient Satisfaction Index). Outcomes were compared to a historical cohort of 29 patients who received intradiscal injections of < 5X PRP. RESULTS: Pain and FRI scores significantly improved by 3.4 ± 2.5 and 46.4 ± 27.6, respectively, at 18.3 ± 13.3 months following intradiscal injections of > 10 × PRP (p < 0.001). These improvements were greater than those reported by the historical cohort (1.7 ± 1.6 and 33.7 ± 12.3; p = 0.004 and 0.016, respectively). Additionally, the satisfaction rate was higher in patients receiving > 10 × PRP compared to those receiving < 5 × PRP (81% vs. 55%; p = 0.032). CONCLUSIONS: Findings from this study suggest that clinical outcomes can be optimized by using PRP preparations that contain a higher concentration of platelets. Further research is needed to continue to optimize the composition of PRP used to treat patients with lumbar disc disease.


Assuntos
Deslocamento do Disco Intervertebral , Dor Lombar , Plasma Rico em Plaquetas , Dor nas Costas , Humanos , Deslocamento do Disco Intervertebral/tratamento farmacológico , Deslocamento do Disco Intervertebral/terapia , Dor Lombar/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
7.
Pain Pract ; 22(1): 117-122, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33949082

RESUMO

BACKGROUND: The use of ultrasound (US)-guided intradiscal injection has been described in the literature with the patient lying in the prone position; however, many patients are unable to lie in the prone position. Therefore, we describe an innovative technique of US-guided platelet-rich plasma (PRP) administration in the lumbar intervertebral disc (IVD) of 3 patients with chronic lower back pain who failed to improve with conservative management. CASE SERIES: For all the 3 patients, magnetic resonance imaging showed annular tears of the L5/S1 IVD with broad-based central posterior protrusions. PRP injection was performed with the patients in the lateral decubitus position or modified recovery position. With the transducer initially placed in the short axis to the lumbar spine, the needle was inserted in-plane to the IVD, with the needle trajectory clearly visualized. Once the needle entered the annulus fibrosus, placement of the needle was confirmed by turning the transducer along the long axis of the spine to validate the location of the needle tip inside the IVD. Discus stimulation was performed with contrast administered to elicit each patient's usual pain, and spread of the contrast was confirmed under fluoroscopy. Upon confirmation of the intradiscal location, 3 ml of PRP was administered. CONCLUSIONS: This report described a novel technique demonstrating that US-guided lumbar intradiscal needle placement for PRP administration in patients lying in the lateral decubitus position is feasible.


Assuntos
Disco Intervertebral , Dor Lombar , Humanos , Disco Intervertebral/diagnóstico por imagem , Dor Lombar/diagnóstico por imagem , Dor Lombar/terapia , Vértebras Lombares/diagnóstico por imagem , Ultrassonografia , Ultrassonografia de Intervenção
8.
Neuromodulation ; 23(2): 196-202, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30821901

RESUMO

INTRODUCTION: Disruptions of lumbar intervertebral discs may lead to severe discogenic low back pain (LBP). Severe pain has a deleterious effect on physical function and quality of life. Spinal cord stimulation (SCS) is a robust treatment for many neuropathic pain conditions. New innovations may be well-suited to treat neuropathic chronic LBP, including discogenic pain. The aim of this prospective study was to determine the effect of dorsal root ganglion (DRG) stimulation for a well-selected group of patients with discogenic LBP with no history of previous back surgeries. METHODS: Twenty subjects with confirmed discogenic LBP and no prior history of back surgery underwent trials of DRG stimulation and, if successful with at least 50% pain reduction, were permanently implanted. Subjects rated their pain, disability, quality of life, and mood at baseline, and 14 subjects were followed through 12 months of treatment. RESULTS: Treatment with DRG stimulation reduced LBP ratings (68.3% reduction), from mean 7.20 ± 1.3 at baseline to 2.29 ± 2.1 after 12 months (p = < 0.001). Oswestry ratings of disability significantly decreased (p = < 0.001) from 42.09 ± 12.9 at baseline to 21.54 ± 16.4 after six months of treatment and to 20.1 ± 16.6 after 12 months. The average quality of life EQ-5D index score at baseline was 0.61 ± 0.12 and 0.84 ± 0.13 after 12 months. DISCUSSION: DRG stimulation treatment for discogenic LBP improved the level of pain, function, and quality of life. Further research is necessary into efficacy of DRG stimulation in patients with chronic discogenic LBP and to determine the place of SCS in the treatment algorithm.


Assuntos
Gânglios Espinais/fisiologia , Dor Lombar/terapia , Manejo da Dor/métodos , Medição da Dor/métodos , Estimulação da Medula Espinal/métodos , Adulto , Feminino , Humanos , Dor Lombar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
9.
Zh Vopr Neirokhir Im N N Burdenko ; 84(6): 112-117, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33306308

RESUMO

The widespread prevalence of degenerative spine diseases and achievements in the treatment of these lesions have not yet led to an answer the main question: «What is the etiology of spine degeneration?¼ Treatment will remain symptomatic if primary cause of disease will be unclear. However, improvement of genetic and molecular survey gradually clarifies the mechanisms underlying degenerative processes. The latest knowledge in regenerative medicine seem promising. Nevertheless, further advances in understanding the fundamental processes in human organism are followed by additional questions and unsolved problems. The authors analyzed the best-studied modern theories of degeneration in this brief review devoted to current concepts of intervertebral disc degeneration.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos
10.
Curr Pain Headache Rep ; 23(9): 65, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31359164

RESUMO

PURPOSE OF REVIEW: Discogenic low back pain (DLBP) stems from pathology in one or more intervertebral discs identified as the root cause of the pain. It is the most common type of chronic low back pain (LBP), representing 26-42% of attributable cases. RECENT FINDINGS: The clinical presentation of DLBP includes increased pain when sitting, coughing, or sneezing, and experiencing relief when standing or ambulating. Dermatomal radiation of pain to the lower extremity and neurological symptoms including numbness, motor weakness, and urinary or fecal incontinence are signs of advanced disease with disc prolapse, nerve root compression, or spinal stenosis. Degenerative disc disease is caused by both a decrease in disc nutrient supply causing decreased oxygen, lowered pH, and lessened ability of the intervertebral disc (IVD) to respond to increased load or injury; moreover, changes in the extracellular matrix composition cause weakening of the tissue and skewing the extracellular matrix's (ECM) harmonious balance between catabolic and anabolic factors for cell turnover in favor of catabolism. Thus, the degeneration of the disc causes a shift from type II to type I collagen expression by NP cells and a decrease in aggrecan synthesis leads to dehydrated matrix cells ultimately with loss of swelling pressure needed for mechanical support. Cell-based therapies such as autologous nucleus pulposus cell re-implantation have in animal models and human trials shown improvements in LBP score, retention of hydration in IVD, and increased disc height. Percutaneously delivered multipotent mesenchymal stem cell (MSC) therapy has been proposed as a potential means to uniquely ameliorate discogenic LBP holistically through three mechanisms: mitigation of primary nociceptive disc pain, slow or reversal of the catabolic metabolism, and restoration of disc tissue. Embryonic stem cells (ESCs) can differentiate into cells of all three germ layers in vitro, but their use is hindered related to ethical concerns, potential for immune rejection after transplantation, disease, and teratoma formation. Another similar approach to treating back pain is transplantation of the nucleus pulposus, which, like stem cell therapy, seeks to address the underlying cause of intervertebral disc degeneration by aiming to reverse the destructive inflammatory process and regenerate the proteoglycans and collagen found in healthy disc tissue. Preliminary animal models and clinical studies have shown mesenchymal stem cell implantation as a potential therapy for IVD regeneration and ECM restoration via a shift towards favorable anabolic balance and reduction of pain.


Assuntos
Degeneração do Disco Intervertebral/terapia , Dor Lombar/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Células-Tronco Embrionárias/transplante , Humanos , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/diagnóstico , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Transplante de Células-Tronco Mesenquimais/tendências , Resultado do Tratamento
11.
J Cell Physiol ; 233(10): 6589-6602, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29150945

RESUMO

Discogenic low back pain (DLBP) is extremely common and costly. Effective treatments are lacking due to DLBP's unknown pathogenesis. Currently, there are no in vivo mouse models of DLBP, which restricts research in this field. The aim of this study was to establish a reliable DLBP model in mouse that captures the pathological changes in the disc and allows longitudinal pain testing. The model was generated by puncturing the mouse lumbar discs (L4/5, L5/6, and L6/S1) and removing the nucleus pulposus using a microscalpel under the microscope. Histology, molecular pathways, and pain-related behaviors were examined. Over 12 weeks post-surgery, animals displayed the mechanical, heat, and cold hyperalgesia along with decreased burrowing and rearing. Histology showed progressive disc degeneration with loss of disc height, nucleus pulposus reduction, proteoglycan depletion, and annular fibrotic disorganization. Immunohistochemistry revealed a substantial increase in inflammatory mediators at 2 and 4 weeks. Nerve growth factor was upregulated from 2 weeks to the end of the experiment. Nerve fiber ingrowth was induced in the injured discs after 4 weeks. Disc-puncture also produced an upregulation of neuropeptides in dorsal root ganglia neurons and an activation of glial cells in the spinal cord dorsal horn. These findings indicate that the cellular and structural changes in discs, as well as peripheral and central nervous system plasticity, paralleled persistent, and robust behavioral pain responses. Therefore, this mouse DLBP model could be used to investigate mechanisms underlying discogenic pain, thereby facilitating effective drug screening and development of treatments for DLBP.


Assuntos
Degeneração do Disco Intervertebral/fisiopatologia , Dor Lombar/fisiopatologia , Corno Dorsal da Medula Espinal/fisiopatologia , Punção Espinal , Animais , Sistema Nervoso Central/fisiopatologia , Modelos Animais de Doenças , Gânglios Espinais/fisiopatologia , Humanos , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/cirurgia , Dor Lombar/genética , Dor Lombar/cirurgia , Camundongos , Neuroglia/patologia , Neuropeptídeos/genética , Núcleo Pulposo/fisiopatologia , Corno Dorsal da Medula Espinal/cirurgia
12.
Pain Med ; 18(4): 751-763, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-27570246

RESUMO

Objective: This report conveys 12-month outcomes of subjects treated with intradiscal biacuplasty (IDB) and conservative medical management (CMM) for chronic low back pain of discogenic origin, and results for subjects who elected to receive IDB + CMM 6 months after CMM-alone. Methods: Sixty-three subjects were originally randomized to the IDB + CMM group (N = 29) or CMM-alone (N = 34). Six months following continuous CMM-alone treatment, participants in this study group were permitted to "cross-over" to IDB + CMM (N = 25), and followed for an additional 6 months. The original IDB + CMM study subjects were followed for a total of 12 months (N = 22). Results: Pain reduction at 12 months was statistically significant and clinically meaningful in the original IDB + CMM group compared to baseline. Functional and disability outcomes were also improved statistically and clinically. Fifty-five percent of the IDB + CMM patients responded to treatment with a mean VAS reduction of 2.2 points at 12 months. Furthermore, 50% and 64% of subjects reported clinically significant improvements in SF36-PF and in ODI, respectively. There was a 1.7-point reduction (improvement) on a 7-point PGIC scale, and a 0.13-point increase (improvement) in the EQ-5D Health Index. Fifty-percent of cross-over subjects responded to IDB + CMM intervention. Mean outcome scores for cross-over subjects were similar to those of the originally-treated subjects, and functional and disability endpoints were improved statistically and clinically compared to respective baseline values. Conclusions: The study demonstrated long-term clinical effectiveness of IDB + CMM for treating chronic lumbar discogenic pain. Furthermore, the cross-over study subjects experienced similar improvements in pain, function, disability, and satisfaction.


Assuntos
Ablação por Cateter/métodos , Dor Crônica/prevenção & controle , Hipertermia Induzida/métodos , Degeneração do Disco Intervertebral/terapia , Dor Lombar/prevenção & controle , Adolescente , Adulto , Idoso , Dor Crônica/diagnóstico , Dor Crônica/etiologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/diagnóstico , Estudos Longitudinais , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Recuperação de Função Fisiológica , Resultado do Tratamento , Estados Unidos , Adulto Jovem
13.
Pain Med ; 17(4): 650-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26893114

RESUMO

OBJECTIVES: This study assessed the effectiveness of percutaneous endoscopic lumbar annuloplasty and nucleoplasty (PELAN) for the treatment of patients with discogenic low back pain. STUDY DESIGN: Retrospective design SETTING: Spine hospital SUBJECTS: Forty-seven patients diagnosed as having discogenic low back pain, who were refractory to conservative treatments. METHODS: Outcomes were assessed using a numeric rating scale for back pain, the Oswestry disability index, and modified MacNab's criteria, at 2-3 weeks and at least 12 months after treatment. RESULTS: At long-term follow-up, 33 patients (70%) had successful outcomes for relief of pain, and the same proportion had successful reduction of disability. Although all patients took oral analgesics for pain control before PELAN, 25 (53%) required no analgesics at long-term follow-up. If success is defined as simultaneously achieving greater than 50% reduction in pain, greater than 40% reduction of disability, good or excellent MacNab criteria, and no need for analgesics, 23 patients (49%; with 95% confidence interval of 35-63%) achieved successful outcomes. CONCLUSIONS: In patients with discogenic low back pain refractory to conservative treatment, PELAN provided favorable clinical outcomes with success rates that rival those of surgery for this condition.


Assuntos
Discotomia Percutânea/métodos , Disco Intervertebral/cirurgia , Dor Lombar/cirurgia , Adolescente , Adulto , Idoso , Feminino , Humanos , Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Int Orthop ; 40(1): 135-40, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26156727

RESUMO

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Transplante de Medula Óssea/métodos , Degeneração do Disco Intervertebral/terapia , Dor Lombar/terapia , Transplante Autólogo/métodos , Adolescente , Adulto , Idoso , Transplante de Medula Óssea/efeitos adversos , Feminino , Seguimentos , Humanos , Dor Lombar/etiologia , Vértebras Lombares/patologia , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Masculino , Células-Tronco Mesenquimais , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Substituição Total de Disco/efeitos adversos , Transplante Autólogo/efeitos adversos , Adulto Jovem
15.
Pain Med ; 16(2): 266-73, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25393059

RESUMO

OBJECTIVE: This study is a pilot study to assess the clinical outcomes of percutaneous disc decompression using the L'DISQ in patients with lumbar discogenic pain. STUDY DESIGN: An institutional, prospective clinical data analysis. METHODS: We ablated the torn annulus using L'DISQ on 20 patients with axial low back pain for at least 3 months (average 29 months) unresponsive to conservative management. Before the therapeutic procedure, all the patients had been diagnosed with lumbar discogenic pain through provocation discography, which had confirmed the level of painful discs. The torn annulus was identified through lumbosacral magnetic resonance image and computed tomographic discogram. Baseline data were prospectively gathered before the procedure and at 1, 4, 12, 24, and 48 weeks post-procedure. Data included pain intensity (visual analog scale [VAS]), measure of disability (Oswestry Disability Index [ODI] and Rolando-Morris Disability Questionnaire [RM]), and health-related quality of life (Bodily Pain Scale of Short Form-36 version 2 [SF-36 BP]). RESULTS: At 48 weeks, the VAS fell from 7.55 ± 1.28 to 3.60 ± 2.28 scores, the ODI and RM had decreased significantly, and the SF-36 BP showed significant improvement (P < 0.05). The success rates of procedure were 55.0% at 48 weeks. There were no complications with the exception of a minor venous bleeding at the site of needle puncture. CONCLUSIONS: The L'DISQ device is specifically designed to ablate adjacent disc tissue using a wand that can be navigated into a torn annulus. Following ablation, we measured clinically significant pain improvement and decreased disability for patients with axial low back pain.


Assuntos
Descompressão Cirúrgica/instrumentação , Deslocamento do Disco Intervertebral/cirurgia , Adulto , Feminino , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Medição da Dor , Projetos Piloto , Adulto Jovem
16.
Pain Med ; 16(8): 1490-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26217926

RESUMO

BACKGROUND: Between 26% and 42% of chronic low back pain is attributed to internal disc disruption of lumbar intervertebral discs. These prevalence estimates and data characterizing discogenic pain originate largely from research at elite practices, conducted 20 years ago. With few studies since, their concordance with rates in community practice has rarely been addressed. OBJECTIVE: To assess the prevalence and key features of discogenic pain within community-based tertiary practice, and to evaluate the accuracy and clinical utility of discography. DESIGN: This prospective, three-year study of 223 consecutive cases of chronic low back pain used image-guided lumbar discography to identify symptomatic and flanking asymptomatic discs. A subset of patients (n = 195) had previously undergone posterior column blocks to investigate spinal facet and/or sacroiliac joints as contributing pain sources. RESULTS: A total of 644 discs were tested without infection or complication. Positive discograms were recorded in 74% of patients, with 22.9% negative and 3.1% assessed as indeterminate. Among patients receiving both discography and diagnostic blocks, 63% had proven discogenic pain, 18% had pain of mixed etiology and 14% remained undiagnosed. Taking into account all low back pain cases during this study (n = 756), discogenic pain prevalence was 21.8% (95% CI: 17-26%). CONCLUSION: The prevalence of discogenic pain in this community practice is below the range, but within confidence intervals, previously reported. Prevalence is considerably elevated, however, among well-selected patients and discography enabled a firm diagnosis in most such cases. These findings are broadly in keeping with those reached in key publications and support the clinical utility of discography.


Assuntos
Degeneração do Disco Intervertebral/epidemiologia , Deslocamento do Disco Intervertebral/epidemiologia , Disco Intervertebral/patologia , Dor Lombar/epidemiologia , Região Lombossacral , Adulto , Austrália/epidemiologia , Eletrodiagnóstico , Feminino , Humanos , Degeneração do Disco Intervertebral/patologia , Deslocamento do Disco Intervertebral/patologia , Dor Lombar/patologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Prevalência , Estudos Prospectivos , Articulação Sacroilíaca/patologia , Articulação Zigapofisária/patologia
17.
Int J Med Sci ; 12(3): 214-22, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25678838

RESUMO

STUDY DESIGN: Comparative assessment of randomized controlled trials of caudal and lumbar interlaminar epidural injections in chronic lumbar discogenic pain. OBJECTIVE: To assess the comparative efficacy of caudal and lumbar interlaminar approaches of epidural injections in managing axial or discogenic low back pain. SUMMARY OF BACKGROUND DATA: Epidural injections are commonly performed utilizing either a caudal or lumbar interlaminar approach to treat chronic lumbar axial or discogenic pain, which is pain exclusive of that associated with a herniated intervertebral disc, or that is due to degeneration of the zygapophyseal joints, or due to dysfunction of the sacroiliac joints, respectively. The literature on the efficacy of epidural injections in managing chronic axial lumbar pain of presumed discogenic origin is limited. METHODS: The present analysis is based on 2 randomized controlled trials of chronic axial low back pain not caused by disc herniation, radiculitis, or facet joint pain, utilizing either a caudal or lumbar interlaminar approach, with a total of 240 patients studied, and a 24-month follow-up. Patients were assigned to receive either local anesthetic only or local anesthetic with a steroid in each 60 patient group. RESULTS: The primary outcome measure was significant improvement, defined as pain relief and functional status improvement of at least 50% from baseline, which was reported at 24-month follow-ups in 72% who received local anesthetic only with a lumbar interlaminar approach and 54% who received local anesthetic only with a caudal approach. In patients receiving local anesthetic with a steroid, the response rate was 67% for those who had a lumbar interlaminar approach and 68% for those who had a caudal approach at 12 months. The response was significantly better in the lumbar interlaminar group who received local anesthetic only, 77% versus 56% at 12 months and 72% versus 54% at 24 months. CONCLUSION: This assessment shows that in patients with axial or discogenic pain in the lumbar spine after excluding facet joint and SI Joint pain, epidural injections of local anesthetic by the caudal or lumbar interlaminar approach may be effective in managing chronic low back pain with a potential superiority for a lumbar interlaminar approach over a caudal approach.


Assuntos
Anestesia Caudal , Anestésicos Locais/administração & dosagem , Dor Crônica/tratamento farmacológico , Dor Lombar/tratamento farmacológico , Manejo da Dor , Adulto , Dor Crônica/patologia , Feminino , Humanos , Injeções Epidurais , Deslocamento do Disco Intervertebral/tratamento farmacológico , Deslocamento do Disco Intervertebral/patologia , Dor Lombar/fisiopatologia , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Esteroides/administração & dosagem
18.
J Cell Mol Med ; 18(6): 1213-25, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24650225

RESUMO

Intervertebral disc degeneration (IVD) can result in chronic low back pain, a common cause of morbidity and disability. Inflammation has been associated with IVD degeneration, however the relationship between inflammatory factors and chronic low back pain remains unclear. Furthermore, increased levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are both associated with inflammation and chronic low back pain, but whether degenerating discs release sufficient concentrations of factors that induce nociceptor plasticity remains unclear. Degenerating IVDs from low back pain patients and healthy, painless IVDs from human organ donors were cultured ex vivo. Inflammatory and nociceptive factors released by IVDs into culture media were quantified by enzyme-linked immunosorbent assays and protein arrays. The ability of factors released to induce neurite growth and nociceptive neuropeptide production was investigated. Degenerating discs release increased levels of tumour necrosis factor-α, interleukin-1ß, NGF and BDNF. Factors released by degenerating IVDs increased neurite growth and calcitonin gene-related peptide expression, both of which were blocked by anti-NGF treatment. Furthermore, protein arrays found increased levels of 20 inflammatory factors, many of which have nociceptive effects. Our results demonstrate that degenerating and painful human IVDs release increased levels of NGF, inflammatory and nociceptive factors ex vivo that induce neuronal plasticity and may actively diffuse to induce neo-innervation and pain in vivo.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Degeneração do Disco Intervertebral/fisiopatologia , Dor Lombar/etiologia , Dor Lombar/patologia , Neuritos/patologia , Neurônios/patologia , Nociceptividade/fisiologia , Adulto , Animais , Apoptose , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/genética , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Degeneração do Disco Intervertebral/complicações , Dor Lombar/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Neuritos/metabolismo , Neurônios/metabolismo , Células PC12 , RNA Mensageiro/genética , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
19.
Pain Med ; 15(1): 16-31, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24152079

RESUMO

OBJECTIVE: Assess the safety and efficacy of intradiscal fibrin sealant in adults with chronic discogenic low back pain. DESIGN: Prospective, nonrandomized Food and Drug Administration approved pilot study. SETTING: Three centers in the United States. SUBJECTS: Fifteen adults with chronic, single, or contiguous two-level lumbar discogenic pain confirmed through meticulous provocation discography. INTERVENTIONS: Volume- and pressure-controlled intradiscal delivery of BIOSTAT BIOLOGX(®) Fibrin Sealant with the Biostat(®) Delivery Device into symptomatic lumbar disc(s). OUTCOME MEASURES: Assessments were performed at baseline, 72 hours, and 1, 4, 13, 26, 52, and 104 weeks following intervention. Potential adverse events were evaluated with serial assessment of neurological status, radiographic, and magnetic resonance imaging (MRI). Efficacy measures included serial assessments of low back pain visual analog scale (VAS) measurements and the Roland-Morris Disability Questionnaire (RMDQ). RESULTS: Safety neurological assessments, X-ray, and MRI showed no significant changes. Adverse events were reported in nine subjects. Two instances of low back muscle spasm and one case of discitis were the only events considered related to the procedure or product. EFFICACY: Mean low back pain VAS scores (mm) decreased from 72.4 (95% confidence interval 64.6-80.3) at baseline to 31.7 (17.4-46.1), 35.4 (17.7-53.1), and 33.0 (16.3-49.6); mean RMDQ score improved from 15.2 (12.7-17.7) at baseline to 8.9 (5.3-12.5), 6.2 (3.4-9.1), and 5.6 (2.9-8.4) at 26, 52, and 104 weeks, respectively. CONCLUSION: Intradiscal injection of BIOSTAT BIOLOGX Fibrin Sealant with the Biostat Delivery Device appears safe and may improve pain and function in selected patients with discogenic pain.


Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Deslocamento do Disco Intervertebral/tratamento farmacológico , Dor Lombar/etiologia , Vértebras Lombares , Adolescente , Adulto , Idoso , Avaliação da Deficiência , Discite/induzido quimicamente , Feminino , Adesivo Tecidual de Fibrina/administração & dosagem , Adesivo Tecidual de Fibrina/efeitos adversos , Seguimentos , Humanos , Injeções Intralesionais , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/patologia , Dor Lombar/diagnóstico por imagem , Dor Lombar/patologia , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Medição da Dor , Projetos Piloto , Estudos Prospectivos , Radiografia , Espasmo/induzido quimicamente , Inquéritos e Questionários , Adulto Jovem
20.
Int J Med Sci ; 11(4): 309-20, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24578607

RESUMO

STUDY DESIGN: A randomized, double-blind, active-controlled trial. OBJECTIVE: To assess the effectiveness of cervical interlaminar epidural injections of local anesthetic with or without steroids for the management of axial or discogenic pain in patients without disc herniation, radiculitis, or facet joint pain. SUMMARY OF BACKGROUND DATA: Cervical discogenic pain without disc herniation is a common cause of suffering and disability in the adult population. Once conservative management has failed and facet joint pain has been excluded, cervical epidural injections may be considered as a management tool. Despite a paucity of evidence, cervical epidural injections are one of the most commonly performed nonsurgical interventions in the management of chronic axial or disc-related neck pain. METHODS: One hundred and twenty patients without disc herniation or radiculitis and negative for facet joint pain as determined by means of controlled diagnostic medial branch blocks were randomly assigned to one of the 2 treatment groups. Group I patients received cervical interlaminar epidural injections of local anesthetic (lidocaine 0.5%, 5 mL), whereas Group II patients received 0.5% lidocaine, 4 mL, mixed with 1 mL or 6 mg of nonparticulate betamethasone. The primary outcome measure was ≥ 50% improvement in pain and function. Outcome assessments included numeric rating scale (NRS), Neck Disability Index (NDI), opioid intake, employment, and changes in weight. RESULTS: Significant pain relief and functional improvement (≥ 50%) was present at the end of 2 years in 73% of patients receiving local anesthetic only and 70% receiving local anesthetic with steroids. In the successful group of patients, however, defined as consistent relief with 2 initial injections of at least 3 weeks, significant improvement was illustrated in 78% in the local anesthetic group and 75% in the local anesthetic with steroid group at the end of 2 years. The results reported at the one-year follow-up were sustained at the 2-year follow-up. CONCLUSIONS: Cervical interlaminar epidural injections with or without steroids may provide significant improvement in pain and functioning in patients with chronic discogenic or axial pain that is function-limiting and not related to facet joint pain.


Assuntos
Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Injeções Epidurais , Cervicalgia/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , Humanos , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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