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1.
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
2.
Spine J ; 14(12): 2976-84, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24912119

RESUMO

BACKGROUND CONTEXT: In canine intervertebral disc (IVD) disease, a useful animal model, only little is known about the inflammatory response in the epidural space. PURPOSE: To determine messenger RNA (mRNA) expressions of selected cytokines, chemokines, and matrix metalloproteinases (MMPs) qualitatively and semiquantitatively over the course of the disease and to correlate results to neurologic status and outcome. STUDY DESIGN/SETTING: Prospective study using extruded IVD material of dogs with thoracolumbar IVD extrusion. PATIENT SAMPLE: Seventy affected and 13 control (24 samples) dogs. OUTCOME MEASURES: Duration of neurologic signs, pretreatment, neurologic grade, severity of pain, and outcome were recorded. After diagnostic imaging, decompressive surgery was performed. METHODS: Messenger RNA expressions of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF), interferon (IFN)γ, MMP-2, MMP-9, chemokine ligand (CCL)2, CCL3, and three housekeeping genes was determined in the collected epidural material by Panomics 2.0 QuantiGene Plex technology. Relative mRNA expression and fold changes were calculated. Relative mRNA expression was correlated statistically to clinical parameters. RESULTS: Fold changes of TNF, IL-1ß, IL-2, IL-4, IL-6, IL-10, IFNγ, and CCL3 were clearly downregulated in all stages of the disease. MMP-9 was downregulated in the acute stage and upregulated in the subacute and chronic phase. Interleukin-8 was upregulated in acute cases. MMP-2 showed mild and CCL2 strong upregulation over the whole course of the disease. In dogs with severe pain, CCL3 and IFNγ were significantly higher compared with dogs without pain (p=.017/.020). Dogs pretreated with nonsteroidal anti-inflammatory drugs revealed significantly lower mRNA expression of IL-8 (p=.017). CONCLUSIONS: The high CCL2 levels and upregulated MMPs combined with downregulated T-cell cytokines and suppressed pro-inflammatory genes in extruded canine disc material indicate that the epidural reaction is dominated by infiltrating monocytes differentiating into macrophages with tissue remodeling functions. These results will help to understand the pathogenic processes representing the basis for novel therapeutic approaches. The canine IVD disease model will be rewarding in this process.


Assuntos
Quimiocina CXCL2/líquido cefalorraquidiano , Descompressão Cirúrgica , Degeneração do Disco Intervertebral/líquido cefalorraquidiano , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/líquido cefalorraquidiano , Deslocamento do Disco Intervertebral/cirurgia , Metaloproteinase 2 da Matriz/líquido cefalorraquidiano , Metaloproteinase 9 da Matriz/líquido cefalorraquidiano , Animais , Modelos Animais de Doenças , Cães , Espaço Epidural/metabolismo , Feminino , Interleucina-1beta/líquido cefalorraquidiano , Interleucina-8/líquido cefalorraquidiano , Masculino , RNA Mensageiro/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano
3.
Artigo em Russo | MEDLINE | ID: mdl-22433801

RESUMO

Using a novel diagnostic technology that allows to investigate the structure of a biological fluid formed during its phase transition into a dried film, we revealed a cause of mistaken results of protein concentrations in the cerebrospinal fluid of patients with discogenic radiculitis. The traditional laboratory study does not reveal the elevated content of protein in patients with discogenic radiculitis and hernia of invertebral discs due to its more active binding with salts with the following sedimentation during centrifugation. It can be explained by the involvement of salt crystals in the formation of the inert organic-mineral aggregate with protein molecules which structure was changed by dystrophy, ischemia, hypoxia, mechanic damage, tumor process. The aggregate is characterized by abnormally tight links. This phenomenon is known as biomineralization, the universal mechanism preventing the organism from toxic effects of products of degraded tissues.


Assuntos
Proteínas do Líquido Cefalorraquidiano/análise , Degeneração do Disco Intervertebral/líquido cefalorraquidiano , Deslocamento do Disco Intervertebral/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Humanos , Sais/líquido cefalorraquidiano , Sais/química
4.
Eur Spine J ; 20(4): 604-11, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21190044

RESUMO

In animal models of degenerative lumbar disease, inducible nitric oxide synthase (iNOS) is expressed in macrophages and Schwann cells following compression of the cauda equina. We previously reported that NO metabolites (nitrite plus nitrate: [NOx]) in the cerebrospinal fluid (CSF) correlate with postoperative pain relief in patients with degenerative lumbar disease and with neurologic recovery rate postoperatively or after conservative treatment in patients with spinal cord injury. The objective of the present study was to examine the relationship between [NOx] and neurologic severity, and recovery in degenerative cervical and lumbar diseases. Two hundred fifty-seven cases, including 85 patients with cervical compression myelopathy (CCM), 25 with cervical disc herniation (CDH), 70 with lumbar canal stenosis (LCS), and 77 with lumbar disc herniation (LDH), were examined. The CSF [NOx] was measured using the Griess method. Severity of neurologic impairment and clinical recovery was assessed using the Japanese Orthopedic Association score and Hirabayashi's method. [NOx] in CCM and LCS, but not CDH and LDH groups, was significantly higher than that in controls, and correlated with postoperative recovery rates, but not with preoperative neurologic severity. [NOx] significantly correlated with neurologic recovery following surgery for CCM and LCS.


Assuntos
Vértebras Cervicais , Degeneração do Disco Intervertebral/líquido cefalorraquidiano , Degeneração do Disco Intervertebral/fisiopatologia , Vértebras Lombares , Óxido Nítrico/líquido cefalorraquidiano , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/líquido cefalorraquidiano , Deslocamento do Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos , Dor Pós-Operatória/epidemiologia , Prevalência , Compressão da Medula Espinal/líquido cefalorraquidiano , Compressão da Medula Espinal/fisiopatologia , Compressão da Medula Espinal/cirurgia , Estenose Espinal/líquido cefalorraquidiano , Estenose Espinal/fisiopatologia , Estenose Espinal/cirurgia , Adulto Jovem
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