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1.
Acta Orthop Traumatol Turc ; 55(3): 246-252, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34100366

RESUMO

OBJECTIVE: The aim of this study was to explore the alterations in levels of pro-inflammatory and catabolic mediators following vertebral fusion in a rabbit model of intervertebral disc degeneration. METHODS: In this study, 24 female New Zealand albino rabbits (aged 4 to 5 months and weighing 3 to 3.5 kg) were used. All the animals were randomly categorized into four groups, and dorsal spinal exposure of all lumbar vertebrae was routinely performed in each group. While disc degeneration was created in groups B, C, and D, spinal fusion was added to disc degeneration in groups C and D. Disc degeneration was typically created by puncturing the discs with an 18-gauge needle under the guidance of C-arm imaging. Fusion was achieved with posterior/posterolateral decortication and iliac bone grafts. The rabbits in groups A, B, and C were euthanized, and the discs were removed in the first week after the surgery. The rabbits in Group D were sacrificed, and the discs were harvested at 5 weeks after the surgery. The levels of Interleukin (IL)-1ß, IL-6, Nitric Oxide (NO), Matrix Metalloproteinase (MMP)-3, MMP-13, and Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) in the discs were analyzed using enzyme-linked immunosorbent assay kits. RESULTS: Significant increase was observed in the protein levels of both pro-inflammatory and catabolic mediators in disc degeneration groups (Group B, C, and D) compared to Group A. In the fusion groups (Group C and D), these increased mediators decreased, compared to non-fusion group (Group B), (IL1-ß P = 0.017, TIMP-1 P = 0.03, NO P = 0.03). However, there was no statistically significant difference in mediator levels between the short- and long-term fusion (Group C versus D). CONCLUSION: The results of this study have shown that a significant decrease in pro-inflammatory and catabolic mediators may be expected after vertebral fusion whereas there may be no significant difference between the first and fourth week of fusion surgery. These findings may contribute to clarifying the mechanism of action of vertebral fusion in the treatment of low back pain.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Animais , Mediadores da Inflamação/análise , Interleucina-1beta/análise , Interleucina-6/análise , Disco Intervertebral/metabolismo , Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/imunologia , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/cirurgia , Dor Lombar/etiologia , Dor Lombar/imunologia , Dor Lombar/prevenção & controle , Metaloproteinase 3 da Matriz/análise , Metabolismo , Óxido Nítrico/análise , Coelhos
2.
Int J Surg Pathol ; 29(3): 314-320, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32666850

RESUMO

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unclear pathogenesis. Collision lesions of CAPNONs with neoplasms are occasionally reported. In this article, we report the first case of collision lesions between CAPNON and rheumatoid nodules (RNs) in a patient with systemic lupus erythematosus. The patient was a 51-year-old female who presented with lower back pain and subsequently a lower back mass over 2 years. Spinal magnetic resonance imaging demonstrated a heterogeneous, partially calcified mass centered in the L3-4 paravertebral regions. A biopsy of the mass was diagnostic of CAPNON. As the mass grew over the following 5 months, it was resected en bloc. Its pathological examination revealed collision lesions of RNs at different histopathological stages and CAPNON lesions, and transitional lesions exhibiting combined RN and CAPNON features, with immune cell infiltrates. Our findings provide new evidence for an immune-mediated reactive process and insights into the pathogenies of CAPNON.


Assuntos
Calcinose/diagnóstico , Dor Lombar/imunologia , Lúpus Eritematoso Sistêmico/complicações , Nódulo Reumatoide/diagnóstico , Músculos do Dorso/patologia , Músculos do Dorso/cirurgia , Biópsia , Calcinose/imunologia , Calcinose/patologia , Calcinose/cirurgia , Feminino , Humanos , Dor Lombar/cirurgia , Vértebras Lombares , Lúpus Eritematoso Sistêmico/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Nódulo Reumatoide/imunologia , Nódulo Reumatoide/patologia , Nódulo Reumatoide/cirurgia , Tomografia Computadorizada por Raios X
3.
Arthritis Rheumatol ; 72(12): 2094-2105, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32638516

RESUMO

OBJECTIVE: This study was undertaken to identify novel autoantibodies in axial spondyloarthritis (SpA) and determine their diagnostic potential in patients with early axial SpA and controls from 2 independent cohorts. METHODS: An axial SpA complementary DNA phage display library was used to screen for novel IgG antibodies in plasma from patients with early axial SpA. The presence of these antibodies against novel peptides (i.e., peptides identified in an early axial SpA cohort from Hasselt University, designated UH-axSpA) was determined by enzyme-linked immunosorbent assay in 76 patients with early axial SpA, 75 controls with nonspecific chronic low back pain, 60 patients with rheumatoid arthritis, and 94 healthy controls from the UH cohort. Antibody reactivity to these novel peptides was further validated in 174 patients with axial SpA (of whom 79 had early axial SpA) from the University Hospitals Leuven (Bio)SPAR (Spondyloarthritis [Biologics]) cohort. RESULTS: We identified antibodies to 9 novel UH-axSpA peptides, corresponding to randomly formed peptides and to a novel axial SpA autoantigen, double homeobox protein 4. Antibodies to 3 UH-axSpA peptides with the highest positive likelihood ratio (LR) for a diagnosis of axial SpA were present in significantly more patients with early axial SpA from the UH and (Bio)SPAR cohorts (14.2% [22/155]) compared to controls with chronic low back pain (5% [4/75]), resulting in 95% specificity. The positive LR for confirming axial SpA using antibodies to these 3 UH-axSpA peptides was 2.7, which is higher than the LR obtained with the currently used laboratory marker C-reactive protein. Testing for antibodies to these 3 UH-axSpA peptides in patients with chronic low back pain increased the posttest probability of a diagnosis of axial SpA from 79% to 91%. CONCLUSION: Antibodies to 3 UH-axSpA peptides could provide a novel tool in the diagnosis of a subset of axial SpA patients.


Assuntos
Autoanticorpos/sangue , Dor Lombar/imunologia , Espondilartrite/imunologia , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Feminino , Humanos , Dor Lombar/sangue , Masculino , Pessoa de Meia-Idade , Espondilartrite/sangue
4.
Expert Rev Clin Pharmacol ; 13(6): 631-639, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32436473

RESUMO

INTRODUCTION: The treatment of chronic low back pain (cLBP) often involves multimodal pharmacologic and non-pharmacologic strategies. There remain shortcomings with these tools with regards to both effect size and side effects. AREAS COVERED: In an effort to better address cLBP, anti-nerve growth factor (NGF) monoclonal antibodies (mAbs) are nearing marketing approval. This class of medications has been primarily evaluated for osteoarthritis, but are being examined at higher doses for use in cLBP. We review the efficacy of this class in treating LBP as well as their potential side effects based on nine phase II or III published clinical trials. Five trials evaluated Tanezumab and four trials evaluated Fasinumab, with seven trials evaluating nonspecific LBP, one evaluating sciatica related cLBP, and one evaluating vertebral fracture related cLBP. EXPERT OPINION: The results of available clinical trials indicate modest effectiveness with regard to reduction of pain in the low back, and improved functionality, compared to placebo in keeping with the effect size of other pharmacologic treatment modalities. Rapidly progressive osteoarthritis was infrequently reported. However, the continued observation of this serious side effects warrants careful patient selection and balancing the risks and benefits of anti-NGF mAbs in treating cLBP.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Dor Lombar/tratamento farmacológico , Fator de Crescimento Neural/imunologia , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Analgésicos/farmacologia , Animais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Dor Crônica/tratamento farmacológico , Dor Crônica/imunologia , Humanos , Dor Lombar/imunologia , Seleção de Pacientes
5.
Eur Spine J ; 29(3): 549-555, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31606818

RESUMO

PURPOSE: To investigate the association between plasma levels of inflammatory cytokines (interleukin [IL]-1-ß, IL-6, tumor necrosis factor [TNF]-α, and the soluble TNF receptor 1 [sTNF-R1]), disability, and risk of falls in older women with acute low back pain (LBP). METHODS: This cross-sectional study comprised a subsample of older women from the Back Complaints in the Elders international cohort study. Plasma levels of IL-1-ß, IL-6, TNF-α, and sTNF-R1 were measured using enzyme-linked immunosorbent assays. Pain was assessed using the Numerical Pain Scale and McGill Pain Questionnaire, while disability was measured using the Roland Morris Questionnaire and gait speed. Risk of falls was estimated using the Physiological Profile Assessment. Linear regression model was used to verify the association between independent variables and fall risk. RESULTS: One hundred and ten women (aged 69.97 ± 5.5 years) with acute LBP were included. The regression model showed an association between the risk of falls and IL-6 levels, pain, gait speed, and years of education. It also explained 21.2% of risk of falls variance. The model equation was: fall risk = 1.28 + (0.19 IL-6) + (0.02 quality of pain) + (- 0.71 gait speed) + (-0 .17 educational level). CONCLUSIONS: This study showed an association between risk of falls and IL-6, pain, gait speed, and educational level in older women with LBP. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Mediadores da Inflamação , Dor Lombar , Idoso , Brasil , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Dor Lombar/epidemiologia , Dor Lombar/imunologia , Pessoa de Meia-Idade
6.
Dokl Biochem Biophys ; 485(1): 145-149, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31201637

RESUMO

Variation of natural antibody (nAb) levels to the pain bioregulators (ß-endorphin, orphanin, serotonin, dopamine, histamine, and angiotensin) in blood serum at chronic low back pain (LBP) was studied for 21 days. We revealed gender features of immuno-profiles: more elevated nAb levels in women at 1st day and equal levels in gender groups at 21st day. In addition, nAb levels remained above normal up to day 21 in most of patients despite a threefold decrease in pain intensity, measured using a differential visual analogue scale. A significant decrease in nAb levels was found in 4-20% of patients depending on the bioregulator. These observations support the hypothesis that antibodies can be a factor in the prolongation of pain. Therefore, the analysis of the dynamics of nAbs can be recommended for patients with LBP, from which it is possible to predict the further course of the disease.


Assuntos
Autoanticorpos/imunologia , Dor Crônica/imunologia , Imunidade Humoral , Dor Lombar/imunologia , Adulto , Autoanticorpos/sangue , Dor Crônica/sangue , Humanos , Dor Lombar/sangue , Masculino , Pessoa de Meia-Idade
7.
Medicine (Baltimore) ; 98(15): e15177, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985704

RESUMO

INTRODUCTION: Low back pain (LBP) is ranked as one of the most prevalent health conditions. It is likely that some inflammatory mediators could be associated with pain and disability in these patients. Photobiomodulation therapy (PBMT) is a non-pharmacological therapy often used in patients with LBP and one of the possible mechanisms of action of therapy is modulate inflammatory mediators. However, to date there are no studies that evaluated the effects of PBMT on the levels of inflammatory mediators in patients with LBP. The aim of this study is to evaluate the acute effects of PBMT on systemic levels of inflammatory mediators and pain intensity in patients with chronic non-specific low back pain. METHODS AND ANALYSIS: This is a prospectively registered, two-arm randomized placebo-controlled trial with blinded patients, assessors and therapists. Eighteen patients with chronic non-specific LBP will be randomized into 2 groups: placebo or active PBMT. The treatment will be provided in a single session. The primary outcome will be levels of prostaglandin E2 (PGE2). The secondary outcomes will be levels of necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and pain intensity. Biochemical and clinical outcomes will be measured at baseline and 15 minutes after the single treatment session. DISCUSSION: Despite PBMT be used in musculoskeletal disorders such as LBP, to the best of our knowledge this is the first study that will investigate a possible biological mechanism behind the positive clinical effects of PBMT on non-specific chronic low back pain. ETHICS AND DISSEMINATION: The study was approved by the Regional Research Ethics Committee. The results will be disseminated through publication in peer-reviewed international journal and conferences. TRIAL REGISTRATION NUMBER: NCT03859505.


Assuntos
Dor Crônica/imunologia , Dor Crônica/terapia , Dor Lombar/imunologia , Dor Lombar/terapia , Terapia com Luz de Baixa Intensidade , Adulto , Protocolos Clínicos , Dinoprostona/metabolismo , Método Duplo-Cego , Feminino , Humanos , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Medição da Dor , Seleção de Pacientes , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
9.
J Mol Med (Berl) ; 97(1): 25-35, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30397790

RESUMO

Latent infection of Propionibacterium acnes was considered as a new pathogeny for low back pain (LBP); however, there is no credible animal evidence or mechanism hypothesis. This study proved that P. acnes is a causative pathogen of bacteria-induced LBP and investigated its underlying mechanism. For this, P. acnes was firstly identified in patients' degenerated intervertebral disc (IVDs) samples. The results of patients' Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Japanese Orthopaedic Association (JOA), and Oswestry Disability Index (ODI) scores indicated that P. acnes-positive patients showed more severe LBP and physical disability. Then, a P. acnes-inoculated lumbar IVDs model was established in rats. The results of paw/foot withdrawal threshold and qRT-PCR indicated that P. acnes-inoculated rats had obvious LBP in behavioral evaluation and over-expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in IVDs. Subsequently, enzyme-linked immunosorbent assay (ELISA) results demonstrated that increased expression of IL-8 or CINC-1 (the homolog of IL-8 in rats) in the P. acnes-positive IVDs of human and rats. The CINC-1 injected animal model proved that the cytokines were able to induce LBP. Finally, the co-culture experiments showed that nucleus pulposus cells (NPCs) were able to respond to P. acnes and secreted IL-8/CINC-1 via TLR-2/NF-κB p65 pathway. In conclusion, P. acnes had strong association with LBP by stimulating NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway. The finding may provide a promising alternative therapy strategy for LBP in clinical. KEY MESSAGES: Patients with P. acnes-positive IVDs tended to have more severe LBP, physical disability, and increased IL-8 expressions. P. acnes can induce LBP via IL-8/CINC-1 in IVDs. P. acnes stimulate the NPCs to secrete pro-algesic factor of IL-8/CINC-1 via TLR2/NF-κBp65 pathway.


Assuntos
Quimiocina CXCL1/imunologia , Infecções por Bactérias Gram-Positivas/complicações , Interleucina-8/imunologia , Degeneração do Disco Intervertebral/microbiologia , Dor Lombar/microbiologia , Propionibacterium acnes/imunologia , Animais , Células Cultivadas , Quimiocina CXCL1/análise , Infecções por Bactérias Gram-Positivas/imunologia , Infecções por Bactérias Gram-Positivas/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Interleucina-8/análise , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/imunologia , Dor Lombar/complicações , Dor Lombar/imunologia , Núcleo Pulposo/imunologia , Núcleo Pulposo/microbiologia , Núcleo Pulposo/patologia , Propionibacterium acnes/fisiologia , Ratos , Transdução de Sinais , Receptor 2 Toll-Like/análise , Receptor 2 Toll-Like/imunologia , Fator de Transcrição RelA/análise , Fator de Transcrição RelA/imunologia
10.
Arthritis Res Ther ; 20(1): 251, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400975

RESUMO

Lumbar disc herniation (LDH) is highly associated with inflammation in the context of low back pain. Currently, inflammation is associated with adverse symptoms related to the stimulation of nerve fibers that may lead to pain. However, inflammation has also been indicated as the main factor responsible for LDH regression. This apparent controversy places inflammation as a good prognostic indicator of spontaneous regression of LDH. This review addresses the molecular and cellular mechanisms involved in LDH regression, including matrix remodeling and neovascularization, in the scope of the clinical decision on conservative versus surgical intervention. Based on the evidence, a special focus on the inflammatory response in the LDH context is given, particularly in the monocyte/macrophage role. The phenomenon of spontaneous regression of LDH, extensively reported in the literature, is therefore analyzed here under the perspective of the modulatory role of inflammation.


Assuntos
Degeneração do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Dor Lombar/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Humanos , Inflamação/diagnóstico por imagem , Inflamação/epidemiologia , Inflamação/imunologia , Degeneração do Disco Intervertebral/epidemiologia , Degeneração do Disco Intervertebral/imunologia , Deslocamento do Disco Intervertebral/epidemiologia , Deslocamento do Disco Intervertebral/imunologia , Dor Lombar/epidemiologia , Dor Lombar/imunologia , Vértebras Lombares/imunologia , Remissão Espontânea
11.
Acta Pharmacol Sin ; 39(6): 912-922, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29795361

RESUMO

Lower back pain (LBP) is the most common disease in orthopedic clinics world-wide. A classic Fangji of traditional Chinese medicine, Duhuo Jisheng Decoction (DHJSD), has been proven clinically effective for LBP but its therapeutic mechanisms remain unclear. We hypothesized that DHJSD might relieve LBP through inhibiting the exaggerated proinflammatory cytokines and extracellular matrix (ECM) degradation. Thus, we studied the effects of DHJSD on stromal cell-derived factor-1 (SDF-1)-induced inflammation and ECM degradation in human nucleus pulposus cells (hNPCs). The primary hNPCs were isolated from either degenerated human intervertebral disc (HID) of LBP patients or normal HID of lumbar vertebral fracture patients, and cultured in vitro. The cells were treated with SDF-1 (10 ng/mL) and subsequently with different concentrations (100-500 µg/mL) of DHJSD for 24 h, respectively. We found that application of DHJSD significantly antagonized the SDF-1-induced production of proinflammatory cytokines and reduction of aggrecan and type II collagen in the hNPCs. DHJSD also markedly reduced the SDF-1-induced increase of CXCR4 and p-p65 and inhibited the nuclear translocation of p65 in the hNPCs. DHJSD, CXCR4-siRNA, and NF-κB inhibitor (BAY11-7082) caused the same inhibition of exaggerated proinflammatory cytokines in the SDF-1-treated hNPCs. These results provided compelling evidence that DHJSD may inhibit the generation of proinflammatory mediators and ECM degradation of HID through an orchestrated targeting at multiple molecules in the SDF-1/CXCR4/NF-κB pathway, thus offered novel mechanistic insights into the clinical effectiveness of DHJSD on LBP.


Assuntos
Anti-Inflamatórios/farmacologia , Quimiocina CXCL12/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Matriz Extracelular/metabolismo , Degeneração do Disco Intervertebral/tratamento farmacológico , Dor Lombar/tratamento farmacológico , Vértebras Lombares/efeitos dos fármacos , NF-kappa B/metabolismo , Núcleo Pulposo/efeitos dos fármacos , Receptores CXCR4/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Células Cultivadas , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Degeneração do Disco Intervertebral/imunologia , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Dor Lombar/imunologia , Dor Lombar/metabolismo , Dor Lombar/patologia , Vértebras Lombares/imunologia , Vértebras Lombares/metabolismo , Vértebras Lombares/patologia , Masculino , Metaloproteinases da Matriz Secretadas/metabolismo , Pessoa de Meia-Idade , Núcleo Pulposo/imunologia , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Receptores CXCR4/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Adulto Jovem
12.
Sci Rep ; 7(1): 12492, 2017 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-28970490

RESUMO

Low back pain (LBP) is a widespread debilitating disorder of significant socio-economic importance and intervertebral disc (IVD) degeneration has been implicated in its pathogenesis. Despite its high prevalence the underlying causes of LBP and IVD degeneration are not well understood. Recent work in musculoskeletal degenerative diseases such as osteoarthritis have revealed a critical role for immune cells, specifically mast cells in their pathophysiology, eluding to a potential role for these cells in the pathogenesis of IVD degeneration. This study sought to characterize the presence and role of mast cells within the IVD, specifically, mast cell-IVD cell interactions using immunohistochemistry and 3D in-vitro cell culture methods. Mast cells were upregulated in painful human IVD tissue and induced an inflammatory, catabolic and pro-angiogenic phenotype in bovine nucleus pulposus and cartilage endplate cells at the gene level. Healthy bovine annulus fibrosus cells, however, demonstrated a protective role against key inflammatory (IL-1ß and TNFα) and pro-angiogenic (VEGFA) genes expressed by mast cells, and mitigated neo-angiogenesis formation in vitro. In conclusion, mast cells can infiltrate and elicit a degenerate phenotype in IVD cells, enhancing key disease processes that characterize the degenerate IVD, making them a potential therapeutic target for LBP.


Assuntos
Anel Fibroso/metabolismo , Condrócitos/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Dor Lombar/metabolismo , Mastócitos/metabolismo , Neovascularização Patológica/metabolismo , Núcleo Pulposo/metabolismo , Adulto , Idoso , Animais , Anel Fibroso/imunologia , Anel Fibroso/patologia , Bovinos , Comunicação Celular/genética , Comunicação Celular/imunologia , Linhagem Celular , Condrócitos/imunologia , Condrócitos/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/imunologia , Degeneração do Disco Intervertebral/patologia , Dor Lombar/genética , Dor Lombar/imunologia , Dor Lombar/patologia , Masculino , Mastócitos/imunologia , Mastócitos/patologia , Pessoa de Meia-Idade , Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Neovascularização Patológica/patologia , Núcleo Pulposo/imunologia , Núcleo Pulposo/patologia , Cultura Primária de Células , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/imunologia
13.
J Pain ; 18(10): 1253-1269, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28652204

RESUMO

Intervertebral disc degeneration (DD) is a cause of low back pain (LBP) in some individuals. However, although >30% of adults have DD, LBP only develops in a subset of individuals. To gain insight into the mechanisms underlying nonpainful versus painful DD, human cerebrospinal fluid (CSF) was examined using differential expression shotgun proteomic techniques comparing healthy control participants, subjects with nonpainful DD, and patients with painful DD scheduled for spinal fusion surgery. Eighty-eight proteins were detected, 27 of which were differentially expressed. Proteins associated with DD tended to be related to inflammation (eg, cystatin C) regardless of pain status. In contrast, most differentially expressed proteins in DD-associated chronic LBP patients were linked to nerve injury (eg, hemopexin). Cystatin C and hemopexin were selected for further examination using enzyme-linked immunosorbent assay in a larger cohort. While cystatin C correlated with DD severity but not pain or disability, hemopexin correlated with pain intensity, physical disability, and DD severity. This study shows that CSF can be used to study mechanisms underlying painful DD in humans, and suggests that while painful DD is associated with nerve injury, inflammation itself is not sufficient to develop LBP. PERSPECTIVE: CSF was examined for differential protein expression in healthy control participants, pain-free adults with asymptomatic intervertebral DD, and LBP patients with painful intervertebral DD. While DD was related to inflammation regardless of pain status, painful degeneration was associated with markers linked to nerve injury.


Assuntos
Degeneração do Disco Intervertebral/líquido cefalorraquidiano , Dor Lombar/líquido cefalorraquidiano , Traumatismos dos Nervos Periféricos/líquido cefalorraquidiano , Proteoma , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Estudos Transversais , Cistatina C/líquido cefalorraquidiano , Feminino , Hemopexina/líquido cefalorraquidiano , Humanos , Inflamação/líquido cefalorraquidiano , Inflamação/complicações , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/imunologia , Dor Lombar/complicações , Dor Lombar/imunologia , Masculino , Pessoa de Meia-Idade , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/imunologia , Proteômica , Adulto Jovem
14.
Scand J Rheumatol ; 46(4): 296-302, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27600931

RESUMO

OBJECTIVES: To investigate whether antibody response patterns against Klebsiella pneumoniae capsular serotypes can discriminate patients with axial spondyloarthritis (axSpA) from patients with non-specific low back pain (LBP). METHOD: Immunoglobulin (Ig)G and IgA antibodies against K. pneumoniae capsular serotypes K2, K26, K36, and K50 were measured, and antibody seropositivity compared between groups and analysed for patient correlation in five different groups: (a) 96 patients fulfilling the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA; (b) 38 patients with either a positive magnetic resonance imaging (MRI) scan as defined by ASAS or a positive human leucocyte antigen (HLA)-B27 status plus one clinical SpA feature, characterized as 'non-axSpA'; (c) 82 non-specific LBP patients; (d) 40 healthy blood donors and (e) 43 patients with diagnosed ankylosing spondylitis (AS) served as the negative and positive control groups. RESULTS: There was no difference in IgG and IgA seropositivity against all serotypes between the axSpA, non-axSpA, and LBP groups. No significant correlations were found between anti-Klebsiella antibodies and age, gender, HLA-B27, or high-sensitivity C-reactive protein (hsCRP). IgG seropositivity against K50 was more frequent in AS (25.6%) than in axSpA (13.5%, p < 0.05). axSpA patients with radiographic sacroiliitis and AS controls concordantly had the highest frequency of seropositivity for ≥ 2 serotypes (21%). CONCLUSIONS: The antibody patterns against K. pneumoniae serotypes K2, K26, K36, and K50 did not discriminate between early axSpA and non-specific LBP.


Assuntos
Anticorpos Antibacterianos/imunologia , Klebsiella pneumoniae/imunologia , Dor Lombar/imunologia , Sacroileíte/imunologia , Espondiloartropatias/imunologia , Adolescente , Adulto , Cápsulas Bacterianas/imunologia , Proteína C-Reativa/imunologia , Estudos de Casos e Controles , Dinamarca , Feminino , Antígeno HLA-B27/genética , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imageamento por Ressonância Magnética , Masculino , Sacroileíte/diagnóstico por imagem , Sacroileíte/genética , Sorogrupo , Espondiloartropatias/diagnóstico por imagem , Espondiloartropatias/genética , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/genética , Espondilite Anquilosante/imunologia , Adulto Jovem
16.
Expert Opin Biol Ther ; 17(2): 245-254, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27936977

RESUMO

INTRODUCTION: The management of pain associated with chronic musculoskeletal conditions represents a significant challenge for the clinician. There remains a need for novel medications that have a significant analgesic benefit and are also safe and well tolerated. Both pre-clinical and clinical data have provided evidence of the role of nerve growth factor (NGF) in a multitude of pain eliciting conditions. Therefore, the development of monoclonal antibodies to NGF for chronic painful musculoskeletal conditions has generated interest. Areas covered: This manuscript is a review that examines both the pharmacological properties and clinical studies of tanezumab, the most widely studied antibody to NGF, for management of osteoarthritis (OA) and low back pain. In addition, the safety and tolerability profile and development history of tanezumab are also discussed. Expert opinion: Most studies provide strong support for the ability of tanezumab to provide clinically meaningful pain relief in individuals with these conditions, with longer-term studies suggesting durability of effect. The adverse event profile appears favorable, assuming the risk mitigation strategies are effective at reducing the incidence of joint-related side effects. Further data are being collected to define the optimal dose and dosing strategy in both OA and chronic low back pain.


Assuntos
Anticorpos Monoclonais Humanizados/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Musculoesqueléticas/tratamento farmacológico , Doenças Musculoesqueléticas/metabolismo , Receptor de Fator de Crescimento Neural/metabolismo , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Doença Crônica , Ensaios Clínicos como Assunto/métodos , Humanos , Dor Lombar/tratamento farmacológico , Dor Lombar/imunologia , Dor Lombar/metabolismo , Doenças Musculoesqueléticas/imunologia , Fator de Crescimento Neural/imunologia , Fator de Crescimento Neural/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/imunologia , Osteoartrite/metabolismo , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Receptor de Fator de Crescimento Neural/imunologia , Resultado do Tratamento
17.
Scand J Rheumatol ; 45(4): 321-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26982485

RESUMO

OBJECTIVES: To estimate the prevalence of inflammatory back pain (IBP) characteristics and analyse the discriminative value of IBP relative to axial spondyloarthritis (SpA) according to the Assessment of SpondyloArthritis international Society (ASAS) criteria. METHOD: Patients who had low back pain for > 3 months were selected from a cohort of secondary care patients aged 18-40 years. Data included information on SpA features, human leucocyte antigen (HLA)-B27 typing, C-reactive protein (CRP) level, magnetic resonance imaging (MRI) of the sacroiliac joints, and self-reported IBP questions covering the pain characteristics included in the Calin, Berlin, and ASAS IBP definitions. RESULTS: Of the 759 included patients, 99% [95% confidence interval (CI) 98-100] had at least one IBP characteristic. The prevalence of the single IBP characteristics ranged from 10% (95% CI 7-12) for 'pain worst in the morning' to 79% (95% CI 76-82) for 'morning stiffness'. Two-thirds of the patients (67%, 95% CI 63-70), met at least one of the three IBP definitions. In all, 86 (11%) were classified as 'SpA according to ASAS'. All three IBP definitions were significantly associated with 'SpA according to ASAS'; however, the discriminative value was low, with sensitivity, specificity, and balanced accuracy values of 64, 50, and 57% for Calin, 59, 60, and 60% for Berlin, and 35, 79, and 57% for ASAS IBP definitions, respectively. CONCLUSIONS: In this study population, IBP characteristics were in general common and the discriminative value was low, as IBP could not differentiate patients with SpA according to ASAS criteria from patients with other causes of back pain.


Assuntos
Ritmo Circadiano , Dor Lombar/diagnóstico , Articulação Sacroilíaca/diagnóstico por imagem , Espondiloartropatias/diagnóstico , Adulto , Proteína C-Reativa/imunologia , Estudos de Coortes , Feminino , Antígeno HLA-B27/genética , Humanos , Inflamação , Dor Lombar/imunologia , Dor Lombar/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Autorrelato , Sensibilidade e Especificidade , Espondiloartropatias/genética , Espondiloartropatias/imunologia , Espondiloartropatias/fisiopatologia , Inquéritos e Questionários , Fatores de Tempo
18.
Osteoarthritis Cartilage ; 23(12): 2242-2251, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26117175

RESUMO

OBJECTIVE: Lumbar facet joint degeneration (FJD) may be an important cause of low back pain (LBP) and sciatica. The goal of this study was to characterize cellular alterations of inflammatory factor expression and neovascularization in human degenerative facet joint capsular (FJC) tissue. These alterations in FJC tissues in pain stimulation were also assessed. DESIGN: FJs were obtained from consented patients undergoing spinal reconstruction surgery and cadaveric donors with no history of back pain. Histological analyses of the FJs were performed. Cytokine antibody array and quantitative real-time polymerase chain reaction (qPCR) were used to determine the production of inflammatory cytokines, and western blotting analyses (WB) were used to assay for cartilage-degrading enzymes and pain mediators. Ex vivo rat dorsal root ganglion (DRG) co-culture with human FJC tissues was also performed. RESULTS: Increased neovascularization, inflammatory cell infiltration, and pain-related axonal-promoting factors were observed in degenerative FJCs surgically obtained from symptomatic subjects. Increased VEGF, (NGF/TrkA), and sensory neuronal distribution were also detected in degenerative FJC tissues from subjects with LBP. qPCR and WB results demonstrated highly upregulated inflammatory cytokines, pain mediators, and cartilage-degrading enzymes in degenerative FJCs. Results from ex vivo co-culture of the DRG and FJC tissue demonstrated that degenerative FJCs increased the expression of inflammatory pain molecules in the sensory neurons. CONCLUSION: Degenerative FJCs possess greatly increased inflammatory and angiogenic features, suggesting that these factors play an important role in the progression of FJD and serve as a link between joint degeneration and neurological stimulation of afferent pain fibers.


Assuntos
Degeneração do Disco Intervertebral/genética , Cápsula Articular/metabolismo , Dor Lombar/genética , Vértebras Lombares , Osteoartrite da Coluna Vertebral/genética , RNA Mensageiro/metabolismo , Escoliose/genética , Espondilolistese/genética , Articulação Zigapofisária/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Western Blotting , Cadáver , Técnicas de Cocultura , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Gânglios Espinais , Humanos , Imuno-Histoquímica , Degeneração do Disco Intervertebral/imunologia , Degeneração do Disco Intervertebral/metabolismo , Cápsula Articular/imunologia , Dor Lombar/imunologia , Dor Lombar/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Neural/metabolismo , Osteoartrite da Coluna Vertebral/imunologia , Osteoartrite da Coluna Vertebral/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Receptor trkA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Escoliose/imunologia , Escoliose/metabolismo , Espondilolistese/imunologia , Espondilolistese/metabolismo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem , Articulação Zigapofisária/imunologia
19.
Vestn Ross Akad Med Nauk ; (1): 118-24, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26027281

RESUMO

OBJECTIVE: Our aim was to study the possible markers of pain syndrome--indicators of pain sensitivity--pain pressure tolerance thresholds (PPTT), and immuno-indicators--natural antibodies against pain processing mediators (eAb) for evaluation the possibility of its using for a objective pain assessment at chronic low back pain. METHODS: Pain sensitivity was assessed daily and nightly, by measuring the PPTT The natural antibody levels (eAb), were determined in serum by ELISA. Measurement of all parameters were performed at 1st, 10th and 21 days. RESULTS: 173 patients (93 women and 80 men) with chronic low back pain were included in the study. At 1st day most patients had lowered PPTT: 55% of men and 74% during the day, 72% of men and 89% of women at night. Dynamic study has shown a tendency of PPTT normalization in men. The study of diurnal PPTT variations have shown that night PPTT lower than day PPTT on 15-17%. We found gender PPTT differences: PPTT values in women 17-26% lower than in men. Analysis of individual eAb profiles has showed that elevated and high levels of eAb to ß-endorphin, orphanin and histamine have 84%, 78%, 84% women and 82%, 85 and 95% men, respectively. These indicators higher than those for serotonin, dopamine and angiotensin (55%, 65%, 70% in women and 65%, 66%, 66% in men, respectively; p < 0.05). Dynamic study of eAb levels have shown a significant anti-histamine eAbs decrease (23%; p = 0.015) only. CONCLUSION: The pathological changes in pain sensitivity and levels of eAbs to pain-processing mediatos are evidenced. Further investigations are necessary to clarify to role of these variations in pain processing and for use these indicators for objective pain assessment.


Assuntos
Anticorpos/sangue , Dor Lombar , Medição da Dor/métodos , Limiar da Dor , beta-Endorfina , Adulto , Feminino , Humanos , Imunidade Humoral , Dor Lombar/diagnóstico , Dor Lombar/imunologia , Dor Lombar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Percepção da Dor , Reprodutibilidade dos Testes , Fatores Sexuais , Fatores de Tempo , beta-Endorfina/sangue , beta-Endorfina/imunologia
20.
J Biochem ; 158(4): 299-308, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25922201

RESUMO

Low back pain is a common clinical problem that causes disability and impaired quality of life. While the reason behind low back pain was largely considered to be of musculoskeletal origin, the contribution of inflammatory cytokines and oxidative stress could never be overlooked. Exercise has been proven to be an effective approach to treat low back pain. However, the mechanism of the exercise effect on the inflammatory cytokines and oxidative stress is still largely unknown. In this study, we revealed that exercise intervention reduces Toll-like receptor 4 (TLR-4) pathway and enhances Sirtuin 1 (SIRT1) expression in low back pain patients. We also confirmed that exercise up-regulates the expression of peroxisome proliferator-activated receptor-gamma, PPAR-γ coactivator-1 and FoxOs family proteins and also increases the activity of catalase and superoxide dismutase in patients with low back pain. Furthermore, we found that exercise intervention attenuates the oxidative stress, pro-inflammatory cytokine concentrations and p53 expression in patients with low back pain. This study demonstrates that exercise intervention improves low back pain symptoms through regulation of the SIRT1 axis with repression of oxidative stress and TLR-4 inhibition.


Assuntos
Regulação da Expressão Gênica , Dor Lombar/terapia , Exercícios de Alongamento Muscular , Estresse Oxidativo , Treinamento de Força , Sirtuína 1/metabolismo , Receptor 4 Toll-Like/metabolismo , Adulto , Estudos Transversais , Citocinas/sangue , Citocinas/metabolismo , Feminino , Proteína Forkhead Box O1 , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Dor Lombar/sangue , Dor Lombar/imunologia , Dor Lombar/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , PPAR gama/genética , PPAR gama/metabolismo , Medição da Dor , Sirtuína 1/genética , Taiwan , Receptor 4 Toll-Like/genética
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