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1.
Biomolecules ; 11(3)2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652804

RESUMO

In recent years, the interest in oxygen-ozone (O2O3) therapy application has considerably increased in the field of rehabilitation. Despite its widespread use in common clinical practice, the biochemical effects of O2O3 are still far from being understood, although its chemical properties seem to play a pivotal role in exerting its positive effects on different pathological conditions. Indeed, the effectiveness of O2O3 therapy might be partly due to the moderate oxidative stress produced by O3 interactions with biological components. O2O3 therapy is widely used as an adjuvant therapeutic option in several pathological conditions characterized by chronic inflammatory processes and immune over-activation, and most musculoskeletal disorders share these pathophysiological processes. The present comprehensive review depicts the state-of-the-art on the mechanisms of action, safety and effectiveness of O2O3 therapy in the complex scenario of the management of musculoskeletal disorders. Taken together, our findings suggest that O2O3 therapy seems to reduce pain and improve functioning in patients affected by low back pain and knee osteoarthritis, as reported by several studies in the literature. However, to date, further studies are warranted to clearly investigate the therapeutic effects of this promising therapy on other musculoskeletal disorders in the field of rehabilitation.


Assuntos
Doenças Musculoesqueléticas/tratamento farmacológico , Doenças Musculoesqueléticas/metabolismo , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/metabolismo , Oxigênio/uso terapêutico , Ozônio/uso terapêutico , Animais , Fibromialgia/tratamento farmacológico , Fibromialgia/metabolismo , Humanos , Dor Lombar/tratamento farmacológico , Dor Lombar/metabolismo , Cervicalgia/tratamento farmacológico , Cervicalgia/metabolismo
2.
FASEB J ; 35(3): e21414, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33583095

RESUMO

Low back pain (LBP) is a major clinical problem that lacks effective treatments. The sensory innervation in porous vertebral endplates and anxiety contributes to spinal hyperalgesia. We hypothesized that SIRT1 activator resveratrol alleviates LBP and anxiety via promotion of osteogenesis in the porous endplates. The hyperalgesia and anxiety-related behaviors; sensory innervation, inflammation and porosity of endplates; and osteogenic/osteoclastic factors expression were measured following resveratrol treatment after lumbar spine instability (LSI) surgery. To explore whether resveratrol promotes endplates osteogenesis and thus alleviates LBP through activation of SIRT1 in the osteoprogenitor cells of endplates, SIRT1OSX -/- mice were employed. Additionally, the levels of inflammation markers, phosphorylation of cAMP response element-binding protein (pCREB), and brain-derived neurotrophic factor (BDNF) in hippocampus were evaluated. After 4 or 8 weeks LSI surgery, the mice suffered from hyperalgesia and anxiety, which were efficiently attenuated by resveratrol at 8 weeks. Resveratrol treatment-enhanced osteogenesis and decreased endplates porosities accompanied with the reduction of TNFα, IL-1ß, and COX2 levels and CGRP+ nerve fibers innervation in porous endplates. Resveratrol-mediated endplates osteogenesis, decreased endplates porosities, and analgesic and antianxiety effects were abrogated in SIRT1OSX -/- mice. Furthermore, resveratrol relieved inflammation and increased pCREB and BDNF expression in the hippocampus after 8 weeks, which alleviate anxiety-related behaviors. This study provides that resveratrol-mediated porous endplates osteogenesis via the activation of SIRT1 markedly blocked sensory innervation and inflammation in endplates, therefore, alleviating LSI surgery-induced LBP and hippocampus-related anxiety.


Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Dor Lombar/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Resveratrol/farmacologia , Sirtuína 1/efeitos dos fármacos , Animais , Ansiolíticos/farmacologia , Ansiedade/metabolismo , Comportamento Animal/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Dor Lombar/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo
3.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537810

RESUMO

Lower back pain (LBP) is one of the most common reasons for seeking medical advice in orthopedic clinics. Increasingly, research has shown that symptomatic intervertebral disc degeneration (IDD) is mostly related to LBP. This review first outlines the research and findings of studies into IDD, from the physiological structure of the intervertebral disc (IVD) to various pathological cascades. The vicious cycles of IDD are re­described in relation to the analysis of the relationship among the pathological mechanisms involved in IDD. Interestingly, a 'chief molecule' was found, hypoxia­inducible factor­1α (HIF­1α), that may regulate all other mechanisms involved in IDD. When the vicious cycle is established, the low oxygen tension activates the expression of HIF­1α, which subsequently enters into the hypoxia­induced HIF pathways. The HIF pathways are dichotomized as friend and foe pathways according to the oxygen tension of the IVD microenvironment. Combined with clinical outcomes and previous research, the trend of IDD development has been predicted in this paper. Lastly, an early precautionary diagnosis and treatment method is proposed whereby nucleus pulposus tissue for biopsy can be obtained through IVD puncture guided by B­ultrasound when the patient is showing symptoms but MRI imaging shows negative results. The assessment criteria for biopsy and the feasibility, superiority and challenges of this approach have been discussed. Overall, it is clear that HIF­1α is an indispensable reference indicator for the accurate diagnosis and treatment of IDD.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Dor Lombar/metabolismo , Animais , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/patologia , Dor Lombar/diagnóstico por imagem , Dor Lombar/patologia
4.
J Clin Neurosci ; 84: 15-22, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33485592

RESUMO

Advanced glycation end-products (AGEs) have been reported as a possible biomarker of ageing and metabolic diseases; however, its role in the clinical progression of these diseases remains unclear. We aimed to evaluate how AGEs are associated with clinical symptoms and comorbidities in lower back pain (LBP) patients. This prospective cohort study enrolled 636 LBP patients. They were subjected to quantified AGE (qAGE) analysis using skin autofluorescence, and their clinical symptoms and comorbidities, such as diabetes, renal failure with haemodialysis treatment, and osteoporosis, were measured. LBP, lower extremity pain, and numbness were evaluated using a visual analogue scale (VAS). The measured qAGE was significantly higher in subjects with any comorbidity. Age also showed a strong positive correlation with qAGE. qAGE and VAS for leg numbness were positively correlated. Furthermore, in LBP patients under 50-years-old, qAGE was positively correlated with VAS for LBP, lower extremity pain, and numbness. In conclusion, qAGE, as measured by skin autofluorescence measurement, was significantly higher in LBP patients with diabetes and dialysis, as well as in osteoporosis patients. Furthermore, qAGE showed potential as a biomarker for LBP, lower extremity pain, and numbness in patients under 50-years-old. If accumulated AGEs are identified at a young age, researchers should be vigilant for the development of osteoporosis and LBP-related clinical symptoms later in life.


Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Dor Lombar/metabolismo , Adulto , Idoso , Envelhecimento/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Produtos Finais de Glicação Avançada/análise , Humanos , Dor Lombar/complicações , Masculino , Pessoa de Meia-Idade , Imagem Óptica/métodos , Osteoporose/epidemiologia , Estudos Prospectivos , Diálise Renal
5.
Pain Manag ; 11(1): 49-57, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33073695

RESUMO

Aim: To verify the effects of physical exercise on low back pain (LBP) and serum cortisol levels in individuals with chronic LBP. Materials & methods: Randomized controlled trials evaluating the effects of exercise on LBP perception and cortisol levels in adults with nonspecific chronic LBP were included. Results: Four randomized controlled trials were included, with a total of 85 participants in the exercise group and 84 in the control group. The interventions reduced -1.61 (95% CI: -2.36 to -0.85) with inconsistency I2 = 72% (p = 0.031) the LBP level and increased 1.05 (95% CI: 0.22-2.32) with inconsistency I2 = 86% (p < 0.0001) the cortisol levels. Conclusion: The practice of physical exercise for 6 weeks or more reduced LBP levels, whereas the rate of progression of an exercise-training program in people with chronic LBP is greater than 4 weeks, but increased the cortisol serum levels in individuals with LBP.


Assuntos
Dor Crônica/reabilitação , Terapia por Exercício , Hidrocortisona/metabolismo , Dor Lombar/reabilitação , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Dor Crônica/metabolismo , Humanos , Dor Lombar/metabolismo
6.
Spine (Phila Pa 1976) ; 45(24): E1636-E1644, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32947496

RESUMO

STUDY DESIGN: Preclinical studies: Efficacy and toxicological studies on lactic acid (LA)-induced sclerozation in pig lumbar discs. Clinical study: Prospective, randomized, double-blinded, placebo-controlled, single ascending dose study investigating the safety and local tolerability of LA. OBJECTIVE: To determine if LA produces sclerozation of the porcine nucleus pulposus (NP) followed by a phase Ib study to evaluate preliminary safety, tolerability, and efficacy of LA in patients with chronic discogenic low back pain. SUMMARY OF BACKGROUND DATA: Surgical stabilization of a motion segment harboring a painful degenerated disc often affords symptomatic relief. In the present study, the hypothesis was tested that LA can produce sclerozation and stabilization of the NP. METHODS: LA (0.2 mL; 60, 120, or 240 mg/mL) or vehicle was injected into the NP or close to the extra spinal region of spinal nerves of young female pigs. The size of the NP, MRI changes, flexural stiffness, and histology of the disc was studied after up to 84 days of survival. Fifteen patients injected intra discally with placebo (iohexol, 1.5 mL, n = 6) or iohexol plus LA (30, 60, or 120 mg/mL; three patients in each group) were followed for up to 12 months. RESULTS: Injection of LA in the pig reproducibly induced sclerozation of the NP and increased flexural rigidity. Histological changes included generation of connective tissue and increased expression of collagen I. No safety concerns were raised. Adverse events in patients were limited to transiently increased low back pain with no obvious difference between treatment groups. There was indication of lower water content of NP injected with the two highest doses of LA. CONCLUSION: LA has a sclerozing effect on the NP in pigs and patients and is therefore a candidate for further clinical studies powered to determine its potential as a treatment of chronic discogenic low back pain. LEVEL OF EVIDENCE: 2.


Assuntos
Produtos Biológicos/administração & dosagem , Disco Intervertebral/diagnóstico por imagem , Ácido Láctico/administração & dosagem , Dor Lombar/diagnóstico por imagem , Dor Lombar/tratamento farmacológico , /métodos , Animais , Produtos Biológicos/metabolismo , Método Duplo-Cego , Feminino , Humanos , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/metabolismo , Ácido Láctico/metabolismo , Dor Lombar/metabolismo , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/diagnóstico por imagem , Núcleo Pulposo/efeitos dos fármacos , Núcleo Pulposo/metabolismo , Estudos Prospectivos , Suínos , Resultado do Tratamento
7.
Biomed Res Int ; 2020: 4670604, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802846

RESUMO

Purpose: To investigate whether icariin (ICA), a well-known medicine extracted from the stem and leaf of Epimedium brevicornum Maxim, had analgesic effect on lower back pain (LBP) in rats. Methods: In a puncture-induced LBP rat model, the severity of LBP was quantified using the paw/foot withdrawal threshold method after intragastric administration of ICA at a dosage of 50 mg/kg/d or 100 mg/kg/d. The pain-related peptides of substance P (SP) and calcitonin gene-related peptide (CGRP) were also measured in intervertebral disc (IVD) tissue using RT-PCR after ICA treatment. In addition, the expression of cytokine-induced neutrophil chemoattractant-1 (CINC-1) in IVD was quantified using RT-PCR and ELISA examination. Results: ICA treatment resulted in a significant amelioration of mechanical allodynia in a dose-response manner, and the analgesic effect could last for two weeks even during the washout period. More importantly, the mechanism of analgesic pharmacological effect in ICA was to suppress the upregulated CINC-1, the homolog of IL-8 in rats, which is a crucial proalgesic factor contributing to LBP, in IVDs. Conclusion: ICA is a novel herbal extract to relieve LBP, and it may be a promising alternative pain killer in the future.


Assuntos
Quimiocina CXCL1/biossíntese , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperalgesia/metabolismo , Dor Lombar/metabolismo , Animais , Hiperalgesia/tratamento farmacológico , Hiperalgesia/patologia , Dor Lombar/tratamento farmacológico , Dor Lombar/patologia , Masculino , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
Sci Rep ; 10(1): 8899, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483367

RESUMO

As the most common cause of low back pain, the cascade of intervertebral disc (IVD) degeneration is initiated by the disappearance of notochordal cells and progressive loss of proteoglycan (PG). Limited nutrient supply in the avascular disc environment restricts the production of ATP which is an essential energy source for cell survival and function such as PG biosynthesis. The objective of this study was to examine ATP level and PG production of porcine IVD cells under prolonged exposure to hypoxia with physiological glucose concentrations. The results showed notochordal NP and AF cells responded differently to changes of oxygen and glucose. Metabolic activities (including PG production) of IVD cells are restricted under the in-vivo nutrient conditions while NP notochordal cells are likely to be more vulnerable to reduced nutrition supply. Moreover, provision of energy, together or not with genetic regulation, may govern PG production in the IVD under restricted nutrient supply. Therefore, maintaining essential levels of nutrients may reduce the loss of notochordal cells and PG in the IVD. This study provides a new insight into the metabolism of IVD cells under nutrient deprivation and the information for developing treatment strategies for disc degeneration.


Assuntos
Trifosfato de Adenosina/metabolismo , Glucose/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Disco Intervertebral/citologia , Dor Lombar/metabolismo , Proteoglicanas/metabolismo , Idoso , Animais , Hipóxia Celular , Sobrevivência Celular , Células Cultivadas , Humanos , Disco Intervertebral/embriologia , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/complicações , Dor Lombar/etiologia , Pessoa de Meia-Idade , Modelos Animais , Suínos
9.
J Complement Integr Med ; 18(1): 1-7, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32554836

RESUMO

OBJECTIVES: Since 70's, scientific research has analyzed how many acute and chronic issues can affect body systems. In case of depression, chronic pain and overtraining, centrals and peripherals systems act to manage and maintain body adaptations. The aim of this study is to evaluate if the osteopathic treatment can increase the release of Cannabinoid receptor (CB) and promote the linkage with their receptors. CONTENT: Documents research is based on PubMed and Google Scholar databases. Keywords used were "osteopathic treatment", "manual therapy", "endocannabinoid", "beta endorphin (BE)", and " CB1" "massage". From 70 articles collected (published in the last 10 years) 52 were excluded as non-relevant to the study aim. SUMMARY: The Key points have been the similar results found by different authors during different treatment periods and with different doses. From 22 articles examined, 13 have established positive effects on CB increasing post osteopathic treatment, three articles have indicated the most targeted tissues in which the substances are most expressed, two articles indicate how physical activities produce antalgic effects by increasing CB's values. OUTLOOK: As a result of this review, osteopathic manipulation treatment seems to be a valid and effective instrument for the treatment of a series of pathologies such as chronic low back pain, fibromyalgia, spinal cord lesions, myofascial graft point, migraine, GI tract dysfunctions, and depression.


Assuntos
Dor Crônica/metabolismo , Dor Crônica/terapia , Endocanabinoides/metabolismo , Manipulação Osteopática/métodos , Receptores de Canabinoides/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Dor Lombar/metabolismo , Dor Lombar/terapia
10.
Acupunct Med ; 38(6): 388-395, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32429680

RESUMO

BACKGROUND: Activation of the sympathetic nervous system attenuates inflammation via catecholamines. Recent evidence has shown that electroacupuncture (EA) activates neuronal networks involved in the release of dopamine and norepinephrine that control systemic inflammation. In muscle, catecholamines are related to cyclic adenosine monophosphate (cAMP). This signaling molecule has been implicated in recovery from sustained contractile activity, which may induce muscular pain, such as that which occurs during low back pain (LBP). OBJECTIVE: Our aim was to evaluate the effects of EA used for the control of LBP on the activation of the sympathetic nervous system in a randomized controlled clinical trial in athletes. METHODS: Two groups of athletes with acute or chronic low back pain were studied. EA, sham EA and pharmacological treatment (diclofenac sodium) were evaluated. The outcome measures included a pain score represented by a visual analogue scale (VAS) and serum levels of catecholamines quantified by enzyme-linked immunosorbent assay. In addition, blood was collected into chilled heparin tubes, placed in 96-well cell culture plates and incubated with an equal volume of Roswell Park Memorial Institute (RPMI) medium, with lipopolysaccharide (LPS) alone or with catecholamines. Tumor necrosis factor (TNF)-α levels in the supernatants were analyzed. RESULTS: The results indicated that the initial pain ratings did not differ between the groups analyzed. EA induced epinephrine secretion but not norepinephrine or dopamine secretion. Although EA and pharmacological treatment did not differ in terms of pain relief, in vitro epinephrine and norepinephrine reduced TNF-α production in response to LPS stimuli. CONCLUSION: EA activates the sympathetic nervous system and induces the release of epinephrine, which could ameliorate inflammation and protect muscular tissue in addition to relieving pain.


Assuntos
Catecolaminas/metabolismo , Eletroacupuntura , Dor Lombar/terapia , Adolescente , Adulto , Atletas/estatística & dados numéricos , Humanos , Dor Lombar/metabolismo , Masculino , Resultado do Tratamento , Adulto Jovem
11.
Comp Med ; 70(3): 205-215, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32312361

RESUMO

We showed previously that inflammatory mediators, including IL8, in intervertebral disc tissues from patients with discogenic back pain may play a key role in back pain. To investigate the molecular mechanism of IL8 signaling in back pain, we generated a mouse model that conditionally expresses human (h) IL8. We hypothesized that hIL8 levels affect mouse activity and function. Briefly, hIL8 cDNA was inserted into the pCALL2 plasmid, linearized, and injected into mouse embryos. Resulting pCALL2-hIL8 mice were then bred with GDF5-Cre mice to express the transgene in cartilage and intervertebral disc (IVD) tissues. Functional capacities including nest-making and other natural behaviors were measured. Both male and female mice expressing hIL8 showed lower nesting scores than did littermates that did not express hIL8 (n = 14 to 16 per group). At 28 wk of age, mice expressing hIL8 (n = 35) spent more time immobile and eating during each night than littermate controls (n = 33). Furthermore, hIL8-expressing mice traveled shorter distances and at a lower average speed than littermate controls. Thus, in an initial effort to investigate the relationship between this chemokine and mouse behavior, we have documented changes in normal activities in mice conditionally expressing hIL8.


Assuntos
Interleucina-8/metabolismo , Dor Lombar/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Disco Intervertebral/metabolismo , Dor Lombar/etiologia , Masculino , Camundongos , Comportamento de Nidação , Transdução de Sinais
12.
Sci Rep ; 10(1): 3708, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111963

RESUMO

The incidence of intervertebral disc (IVD) degeneration disease, caused by changes in the osmotic pressure of nucleus pulposus (NP) cells, increases with age. In general, low back pain is associated with IVD degeneration. However, the mechanism and molecular target of low back pain have not been elucidated, and there are no data suggesting specific biomarkers of low back pain. Therefore, the research aims to identify and verify the significant gene biomarkers of low back pain. The differentially expressed genes (DEGs) were screened in the Gene Expression Omnibus (GEO) database, and the identification and analysis of significant gene biomarkers were also performed with various bioinformatics programs. A total of 120 patients with low back pain were recruited. Before surgery, the degree of pain was measured by the numeric rating scale (NRS), which enables comparison of the pain scores from individuals. After surgery, IVD tissues were obtained, and NP cells were isolated. The NP cells were cultured in two various osmotic media, including iso-osmotic media (293 mOsm/kg H2O) to account for the morbid environment of NP cells in IVD degeneration disease and hyper-osmotic media (450 mOsm/kg H2O) to account for the normal condition of NP cells in healthy individuals. The relative mRNA expression levels of CCL5, OPRL1, CXCL13, and SST were measured by quantitative real-time PCR in the in vitro analysis of the osmotic pressure experiments. Finally, correlation analysis and a neural network module were employed to explore the linkage between significant gene biomarkers and pain. A total of 371 DEGs were identified, including 128 downregulated genes and 243 upregulated genes. Furthermore, the four genes (CCL5, OPRL1, SST, and CXCL13) were identified as significant gene biomarkers of low back pain (P < 0.001) based on univariate linear regression, and CCL5 (odds ratio, 34.667; P = 0.003) and OPRL1 (odds ratio, 19.875; P < 0.001) were significantly related to low back pain through multivariate logistic regression. The expression of CCL5 and OPRL1 might be correlated with low back pain in patients with IVD degeneration disease caused by changes in the osmotic pressure of NP cells.


Assuntos
Dor Lombar/genética , Núcleo Pulposo/química , Expressão Gênica , Marcadores Genéticos , Humanos , Disco Intervertebral/química , Disco Intervertebral/metabolismo , Disco Intervertebral/cirurgia , Dor Lombar/metabolismo , Dor Lombar/cirurgia , Núcleo Pulposo/metabolismo , Pressão Osmótica , Proteínas/genética , Proteínas/metabolismo
13.
Neuromodulation ; 23(2): 222-233, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32103593

RESUMO

INTRODUCTION: Nociceptive signals from lumbar intervertebral discs ascend in the sympathetic chain via the L2 dorsal root ganglion (L2 DRG), a potential target for discogenic low back pain in neuromodulation. Positron Emission Tomography/Computed Tomography (PET-CT) measures functional changes in the brain metabolic activity, identified by the changes in the regional cerebral blood flow (rCBF) as determined by the changes of F-18 Fluoro-deoxyglucose (18 F FDG) tracer within brain tissues. METHODS AND MATERIALS: Nine patients were recruited to explore the changes in PET-CT imaging at baseline and four-weeks post implantation of bilateral L2 DRG neurostimulation leads and implantable pulse generator (IPG). PET-CT scans were performed 30 min following an IV injection of 250±10% MBq of 18 F FDG tracer. Fifteen frames were acquired in 15 min. PET list-mode raw data were reconstructed and normalized appropriately to a brain anatomical atlas. RESULTS: Nine patients were recruited to the study, where PET-CT imaging data for five patients were analyzed. The right and left insular cortex, primary and secondary somato-sensory cortices, prefrontal cortex, anterior cingulate cortex, thalamus, amygdala, hippocampus and the midline periaqueductal areas, were assessed for any changes in the metabolic activity. A total of 85 pain matrix regions were delineated SUV (standardized uptake value)MAX , SUV MEAN ± SD, and SUVPEAK were calculated for each of these regions of the brain and were compared pre- and post-L2 DRG stimulation. Sixty-one of the 85 matrices showed an increase in metabolic activity whereas 24 matrices showed a reduction in metabolic activity. CONCLUSION: This is the first ever study reporting the changes in cerebral metabolic activity and multi-frame static brain 18 F FDG PET imaging after L2 DRG stimulation for discogenic low back pain. Predominantly an increased metabolic activity in nociceptive brain matrices are seen with an increased in F18 F FDG uptake following L2 DRG stimulation.


Assuntos
Encéfalo/diagnóstico por imagem , Gânglios Espinais/diagnóstico por imagem , Dor Lombar/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estimulação da Medula Espinal/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Encéfalo/metabolismo , Feminino , Fluordesoxiglucose F18 , Gânglios Espinais/metabolismo , Humanos , Dor Lombar/metabolismo , Dor Lombar/terapia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/metabolismo , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos
14.
Tissue Eng Part A ; 26(1-2): 47-56, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31578928

RESUMO

Low back pain is one of the most common disorders and believed to be due to intervertebral disc degeneration. Transplantation of human mesenchymal stem cells (hMSCs) is suggested as potential treatment option. Bone morphogenetic growth factor 3 (BMP-3) promotes chondrogenesis and is proven effective in enhancing chondrogenesis in hMSCs pretreated with interleukin-1 beta (IL-1ß) in hydrogel model. Three-dimensional co-cultures of hMSCs and disc cells (DCs) have previously been demonstrated to result in increased proteoglycan production. The aim was to study the effects of BMP-3 on hMSCs, DCs, as well as hMSCs and DCs in co-culture in a pellet system, both as single treatment and after pretreatment of IL-1ß. Cell pellet cultures with hMSCs, DCs, and co-culture (1:1 ratio) were performed and stimulated with BMP-3 at 1 or 10 ng/mL concentrations. For pretreatment (PRE-T), cell pellets were first stimulated with IL-1ß, for 24 h, and then BMP-3. The pellets were harvested on day 7, 14, and 28. Results demonstrated that BMP-3 stimulation at 10 ng/mL promoted cell viability, proteoglycan accumulation, as well as chondrogenesis in all pellet groups compared to 1 ng/mL. Cellular proliferation and chondrogenic differentiation of hMSCs were best promoted by PRE-T at 10 ng/mL, whereas BMP-3 best enhanced chondrogenesis in DC and co-culture pellets at the same concentration. Impact Statement Current therapies for low back pain include pain modulation and surgery, which do not tackle the underlying cellular mechanisms of the degenerated intervertebral discs (IVDs). To develop an understanding of the degeneration process and to further reverse its course, the effects of growth factor and cytokine on the native cells of the IVDs were investigated, revealing the potency of bone morphogenetic growth factor 3 on disc cells (DCs) and combined culture of mesenchymal stem cells and DCs. These results may impact future strategies in development of cell therapies that could directly influence the IVD degeneration process, which might alter the treatment models of today.


Assuntos
Dor Lombar/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Proteína Morfogenética Óssea 3/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Condrogênese/genética , Condrogênese/fisiologia , Técnicas de Cocultura , Humanos , Imuno-Histoquímica , Interleucina-1beta/metabolismo , Disco Intervertebral/citologia , Disco Intervertebral/metabolismo , Fatores de Transcrição SOX9/metabolismo
15.
Spine J ; 20(2): 199-206, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31563580

RESUMO

BACKGROUND CONTEXT: Low back pain (LBP) in Western Europe was classified as having the highest disability and overall burden among 291 studied conditions. For an extensive period of time, evidence related to morphological changes (eg, atrophy and fat infiltration) of the paraspinal muscles in persons with LBP has accumulated. Despite this evidence, there is limited knowledge on muscle fiber type composition of these muscles, and their relation to LBP. PURPOSE: The aim of the study is to investigate differences in muscle fiber type composition between persons with nonspecific chronic low back pain (NSCLBP) and healthy controls for the lumbar erector spinae (ES) and multifidus (MF) muscle. STUDY DESIGN AND SETTING: A cross-sectional study took place in the REVAL Rehabilitation Research Center, Hasselt University, Diepenbeek, Belgium. PATIENT SAMPLE: Twenty persons with NSCLBP (age: 44.5±7.42) and 18 healthy controls (age: 39.89±7.90) participated in this study. OUTCOME MEASURES: The primary outcome measure was paraspinal muscle fiber type composition. Secondary outcomes consisted of physiologic measures (maximal aerobic capacity and back muscle strength) and functional measures (activity level). METHODS: Biopsy samples were taken from the lumbar ES and MF muscle at the L4 spinal level. These samples were stained using immunofluorescent antibodies against myosin heavy chains. In each sample, number and size (CSA) of type I, I/IIa, IIa, IIa/x, and IIx muscle fibers were quantified. From these data the relative cross-sectional fiber areas (RCSA) were calculated. To analyze differences in fiber type composition between healthy persons and persons with NSCLBP, a repeated measurements analysis of variance was used. Secondary outcome measures were analyzed using a Student's t test, and Wilcoxon test. This study was supported by the research fund of Hasselt University without potential conflict of interest. RESULTS: There were no significant differences between both groups regarding anthropometric data. There were no significant between group differences for CSA in the ES. Persons with NSCLBP displayed a nonsignificant (p=.0978) increase in the number of type I muscle fibers, and a significant decrease (p=.0019) in the number of type IIx muscle fibers in the ES muscle. Persons with NSCLBP also displayed a trend toward a higher (p=.0596) RCSA for type I fibers and a significantly lower RCSA for type IIx fibers (p=.0411). There were no significant between group differences within the MF. Regarding the secondary outcome measures, there was a significant between group difference in activity level (p=.0004) and isokinetic back muscle strength (p=.0342). CONCLUSIONS: This is the first study to examine muscle fiber type characteristics in both the ES and MF muscle of persons with NSCLBP. Based on muscle fiber characteristics, the paraspinal muscles of persons with NSCLBP seems to display a larger oxidative potential based on an increase of the number type I fibers at the expense of type IIx glycolytic fibers.


Assuntos
Glicólise , Dor Lombar/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Adulto , Feminino , Humanos , Dor Lombar/patologia , Masculino , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Músculos Paraespinais/metabolismo , Músculos Paraespinais/patologia
16.
Arthritis Res Ther ; 21(1): 186, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409426

RESUMO

BACKGROUND: Previous studies suggest that regulatory microRNAs (miRs) may modulate neuro-inflammatory processes. The purpose of the present study was to examine the role of miR-17 following intervertebral disc herniation. METHODS: In a cohort of 97 patients with leg pain and disc herniation verified on MRI, we investigated the association between circulating miR-17 and leg pain intensity. A rat model was used to examine possible changes in miR-17 expression in nucleus pulposus (NP) associated with leak of NP tissue out of the herniated disc. The functional role of miR-17 was addressed by transfection of miR-17 into THP-1 cells (human monocyte cell line). RESULTS: An association between the level of miR-17 in serum and the intensity of lumbar radicular pain was shown. Up-regulation of miR-17 in the rat NP tissue when applied onto spinal nerve roots and increased release of TNF following transfection of miR-17 into THP-1 cells were also observed. Hence, our data suggest that miR-17 may be involved in the pathophysiology underlying lumbar radicular pain after disc herniation. CONCLUSIONS: We conclude that miR-17 may be associated with the intensity of lumbar radicular pain after disc herniation, possibly through a TNF-driven pro-inflammatory mechanism.


Assuntos
Deslocamento do Disco Intervertebral/complicações , Dor Lombar/genética , Vértebras Lombares , MicroRNAs/genética , Regulação para Cima , Adolescente , Adulto , Animais , Linhagem Celular , Modelos Animais de Doenças , Feminino , Seguimentos , Humanos , Deslocamento do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/metabolismo , Dor Lombar/etiologia , Dor Lombar/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Ratos , Ratos Endogâmicos Lew , Adulto Jovem
17.
Braz J Med Biol Res ; 52(9): e8525, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31411316

RESUMO

Many compounds of ginsenosides show anti-inflammatory properties. However, their anti-inflammatory effects in intervertebral chondrocytes in the presence of inflammatory factors have never been shown. Increased levels of pro-inflammatory cytokines are generally associated with the degradation and death of chondrocytes; therefore, finding an effective and nontoxic substance that attenuates the inflammation is worthwhile. In this study, chondrocytes were isolated from the nucleus pulposus tissues, and the cells were treated with ginsenoside compounds and IL-1ß, alone and in combination. Cell viability and death rate were assessed by CCK-8 and flow cytometry methods, respectively. PCR, western blot, and immunoprecipitation assays were performed to determine the mRNA and protein expression, and the interactions between proteins, respectively. Monomeric component of ginsenoside Rd had no toxicity at the tested range of concentrations. Furthermore, Rd suppressed the inflammatory response of chondrocytes to interleukin (IL)-1ß by suppressing the increase in IL-1ß, tumor necrosis factor (TNF)-α, IL-6, COX-2, and inducible nitric oxide synthase (iNOS) expression, and retarding IL-1ß-induced degradation of chondrocytes by improving cell proliferation characteristics and expression of aggrecan and COL2A1. These protective effects of Rd were associated with ubiquitination of IL-1 receptor accessory protein (IL1RAP), blocking the stimulation of IL-1ß to NF-κB. Bioinformatics analysis showed that NEDD4, CBL, CBLB, CBLC, and ITCH most likely target IL1RAP. Rd increased intracellular ITCH level and the amount of ITCH attaching to IL1RAP. Thus, IL1RAP ubiquitination promoted by Rd is likely to occur by up-regulation of ITCH. In summary, Rd inhibited IL-1ß-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination.


Assuntos
Condrócitos/efeitos dos fármacos , Ginsenosídeos/farmacologia , Proteína Acessória do Receptor de Interleucina-1/metabolismo , Interleucina-1beta/efeitos dos fármacos , Degeneração do Disco Intervertebral/metabolismo , Adulto , Idoso , Agrecanas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Feminino , Ginsenosídeos/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Dor Lombar/metabolismo , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase/metabolismo , Núcleo Pulposo/citologia , Núcleo Pulposo/efeitos dos fármacos , Núcleo Pulposo/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitinação
18.
Eur Radiol ; 29(12): 6443-6446, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31278582

RESUMO

KEY POINTS: • Molecular intervertebral disc damage was associated with LBP and radiculopathy.• Patients with radiculopathy and LBP demonstrated a depletion of gagCEST values compared with healthy controls.• GagCEST imaging may be a non-invasive tool for investigation of degeneration processes of lumbar intervertebral discs (IVDs). GagCEST imaging may be an imaging biomarker for biochemical IVD alterations.


Assuntos
Degeneração do Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/diagnóstico por imagem , Dor Lombar/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Radiculopatia/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , Glicosaminoglicanos/metabolismo , Humanos , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/metabolismo , Dor Lombar/etiologia , Dor Lombar/metabolismo , Vértebras Lombares/metabolismo , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiculopatia/etiologia , Radiculopatia/metabolismo , Adulto Jovem
19.
Arthritis Res Ther ; 21(1): 165, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277706

RESUMO

OBJECTIVES: Low back pain is the largest contributor to disability worldwide. The role of body composition as a risk factor for back pain remains unclear. Our aim was to examine the relationship between fat mass and fat distribution on back pain intensity and disability using validated tools over 3 years. METHODS: Participants (aged 25-60 years) were assessed at baseline using dual-energy X-ray absorptiometry (DXA) to measure body composition. All participants completed the Chronic Pain Grade Scale at baseline and 3-year follow-up. Of the 150 participants, 123 (82%) completed the follow-up. RESULTS: Higher baseline body mass index (BMI) and fat mass (total, trunk, upper limb, lower limb, android, and gynoid) were all associated with high intensity back pain at either baseline and/or follow-up (total fat mass: multivariable OR 1.05, 95% CI 1.01-1.09, p < 0.001). There were similar findings for all fat mass measures and high levels of back disability. A higher android to gynoid ratio was associated with high intensity back pain (multivariable OR 1.04, 95% CI 1.01-1.08, p = 0.009). There were no associations between lean mass and back pain. CONCLUSIONS: This cohort study provides evidence for the important role of fat mass, specifically android fat relative to gynoid fat, on back pain and disability.


Assuntos
Tecido Adiposo/metabolismo , Composição Corporal/fisiologia , Índice de Massa Corporal , Avaliação da Deficiência , Dor Lombar/fisiopatologia , Obesidade/fisiopatologia , Inquéritos e Questionários , Absorciometria de Fóton , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Dor Lombar/diagnóstico , Dor Lombar/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Medição da Dor/métodos , Vigilância da População/métodos , Fatores de Risco
20.
EBioMedicine ; 43: 487-500, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31047862

RESUMO

BACKGROUND: Low back pain (LBP) is the leading global cause of disability and is associated with intervertebral disc degeneration (DD) in some individuals. However, many adults have DD without LBP. Understanding why DD is painful in some and not others may unmask novel therapies for chronic LBP. The objectives of this study were to a) identify factors in human cerebrospinal fluid (CSF) associated with chronic LBP and b) examine their therapeutic utility in a proof-of-concept pre-clinical study. METHODS: Pain-free human subjects without DD, pain-free human subjects with DD, and patients with chronic LBP linked to DD were recruited and lumbar MRIs, pain and disability levels were obtained. CSF was collected and analyzed by multiplex cytokine assay. Interleukin-8 (IL-8) expression was confirmed by ELISA in CSF and in intervertebral discs. The SPARC-null mouse model of progressive, age-dependent DD and chronic LBP was used for pre-clinical validation. Male SPARC-null and control mice received systemic Reparixin, a CXCR1/2 (receptors for IL-8 and murine analogues) inhibitor, for 8 weeks. Behavioral signs of axial discomfort and radiating pain were assessed. Following completion of the study, discs were excised and cultured, and conditioned media was evaluated with a protein array. FINDINGS: IL-8 was elevated in CSF of chronic LBP patients with DD compared to pain-free subjects with or without DD. Chronic inhibition with reparixin alleviated low back pain behaviors and attenuated disc inflammation in SPARC-null mice. INTERPRETATION: These studies suggest that the IL-8 signaling pathway is a viable therapy for chronic LBP. FUND: Supported by NIH, MMF, CIHR and FRQS.


Assuntos
Interleucina-8/metabolismo , Dor Lombar/etiologia , Dor Lombar/metabolismo , Osteonectina/deficiência , Sulfonamidas/farmacologia , Adulto , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Interleucina-8/líquido cefalorraquidiano , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/diagnóstico , Dor Lombar/diagnóstico , Dor Lombar/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Transdução de Sinais
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