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1.
BMJ ; 367: l5654, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619437

RESUMO

OBJECTIVE: To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes). DESIGN: Double blind, parallel group, placebo controlled, multicentre trial. SETTING: Hospital outpatient clinics at six hospitals in Norway. PARTICIPANTS: 180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017. INTERVENTIONS: Patients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription. MAIN OUTCOME MEASURES: The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4. RESULTS: In the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was -1.6 (95% confidence interval -3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was -2.3 (-4.2 to-0.4, P=0.02) for patients with type 1 Modic changes and -0.1 (-2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group. CONCLUSIONS: In this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323412.


Assuntos
Amoxicilina , Degeneração do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/complicações , Dor Lombar , Vértebras Lombares , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Dor Crônica/diagnóstico , Dor Crônica/tratamento farmacológico , Dor Crônica/etiologia , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Humanos , Dor Lombar/diagnóstico , Dor Lombar/tratamento farmacológico , Dor Lombar/etiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Noruega , Medição da Dor/métodos , Resultado do Tratamento
2.
Arthritis Res Ther ; 21(1): 186, 2019 Aug 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.

3.
Skeletal Radiol ; 48(6): 871-879, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30255192

RESUMO

OBJECTIVE: To examine the impact of demographic, clinical, and genetic factors as well as herniated discs on 5-year development of disc degeneration in the lumbar spine, and to investigate associations between changes in lumbar degenerative findings and pain. MATERIALS AND METHODS: In 144 patients with lumbar radicular pain or low back pain, we scored disc degeneration, herniated discs, and high-intensity zones in the posterior annulus fibrosus on lumbar magnetic resonance imaging (MRI) at baseline and 5-year follow-up. Genotyping (TaqMan assay) was performed for genes encoding vitamin D receptor (VDR), collagen XIα (COL11A), matrix metalloproteinase 1/9 (MMP1/MMP9), and interleukin 1α/1RN (IL-1α/IL-1RN). Associations were analyzed using multivariate linear regression adjusted for age, sex, smoking, body mass index, and baseline scores for degenerated discs and herniated discs (when analyzing impact of baseline factors) or for pain (when analyzing associations with pain). RESULTS: Progression of disc degeneration over 5 years was significantly (p < 0.001) related to higher age and less disc degeneration at baseline, but not to sex, smoking, body mass index, herniated discs, or variants in the studied genes. No associations were identified between changes in disc degeneration or high-intensity zones and pain at 5-year follow-up. However, increased number of herniated discs over 5 years was associated with pain at rest (p = 0.019). CONCLUSIONS: Age and disc degeneration at baseline, rather than genetic factors, influenced the 5-year development of disc degeneration in patients with lumbar radicular pain or low back pain. Development of herniated discs was related to pain at rest.


Assuntos
Degeneração do Disco Intervertebral/diagnóstico por imagem , Imagem por Ressonância Magnética , Adulto , Fatores Etários , Colágeno Tipo XI/genética , Progressão da Doença , Feminino , Genótipo , Humanos , Interleucina-1/genética , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/patologia , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Receptores de Calcitriol/genética
4.
Pain ; 158(7): 1280-1288, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28420008

RESUMO

The aim of this study was to examine whether increases in severity of subclinical inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), increased experimental pain sensitivity, measured by cold-pressor tolerance, and to test whether this relationship is independent of chronic pain. A large population-based study from 2007 to 2008, the sixth Tromsø Study, provided data from 12,981 participants. For the present analysis, complete data for 10,274 participants (age: median 58 years) were available. The main outcome measure was cold-pressor tolerance, tested by placing the dominant hand in circulating cold water (3°C) for a maximum of 106 seconds. Cox proportional hazard models, treating hand withdrawal during the cold-pressor test as the event and enduring the full test time as censored data, were used to investigate the relationship between hs-CRP levels (≤3 or >3 mg/L) and cold-pressure tolerance. The fully adjusted model was controlled for age, sex, education, body mass index, smoking status, alcohol consumption, emotional distress, statin usage, and self-reported presence of chronic pain. Additional analysis was performed in participants without chronic pain. Higher levels of hs-CRP were negatively related to cold-pressor tolerance (hazard ratio [HR] = 1.24, 95% confidence interval [CI], 1.12-1.37, P < 0.001), adjusted for age and sex. This relationship remained essentially unaltered after controlling for potential confounders (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001), as well as for the presence of chronic pain (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001). The present data show that subclinical inflammation is related to increased pain sensitivity, suggesting a potential role of inflammation in experimental pain which may be of importance for the development of clinical pain.


Assuntos
Proteína C-Reativa/metabolismo , Inflamação/sangue , Limiar da Dor/fisiologia , Dor/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Temperatura Baixa , Feminino , Humanos , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Medição da Dor , Fatores Sexuais
5.
PLoS One ; 9(9): e107301, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25207923

RESUMO

Previous studies indicate that lumbar radicular pain following disc herniation may be associated with release of several pro-inflammatory mediators, including interleukin-1 (IL1). In the present study, we examined how genetic variability in IL1A (rs1800587 C>T), IL1B (rs1143627 T>C) and IL1RN (rs2234677 G>A) influenced the clinical outcome the first year after disc herniation. Patients (n = 258) with lumbar radicular pain due to disc herniation were recruited from two hospitals in Norway. Pain and disability were measured by visual analogue scale (VAS) and Oswestry Disability Index (ODI) over a 12 month period. The result showed that patients with the IL1A T allele, in combination with the IL1RN A allele had more pain and a slower recovery than other patients (VAS p = 0.049, ODI p = 0.059 rmANOVA; VAS p = 0.003, ODI p = 0.050 one-way ANOVA at 12 months). However, regarding the IL1B/IL1RN genotype, no clear effect on recovery was observed (VAS p = 0.175, ODI p = 0.055 rmANOVA; VAS p = 0.105, ODI p = 0.214 one-way ANOVA at 12 months). The data suggest that the IL1A T/IL1RN A genotype, but not the IL1B T/IL1RN A genotype, may increase the risk of a chronic outcome in patients following disc herniation.


Assuntos
Dor Crônica/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1alfa/genética , Interleucina-1beta/genética , Deslocamento do Disco Intervertebral/genética , Dor Lombar/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Alelos , Dor Crônica/etiologia , Dor Crônica/fisiopatologia , Dor Crônica/cirurgia , Avaliação da Deficiência , Feminino , Genótipo , Humanos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/cirurgia , Dor Lombar/etiologia , Dor Lombar/fisiopatologia , Dor Lombar/cirurgia , Vértebras Lombares/lesões , Vértebras Lombares/fisiopatologia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Noruega , Medição da Dor , Qualidade de Vida , Inquéritos e Questionários
6.
Skeletal Radiol ; 43(9): 1271-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24965739

RESUMO

OBJECTIVE: To examine whether Modic changes influence pain during a 1-year follow-up in patients with lumbar radicular pain. MATERIALS AND METHODS: A total of 243 patients with lumbar radicular pain due to disc herniation were recruited from two hospitals in Norway and followed up at 6 weeks, 6 months, and 12 months. On baseline lumbar magnetic resonance images, two observers independently evaluated Modic changes (types I-III; craniocaudal size 0-3). Outcomes were sensory pain (McGill Pain Questionnaire), back and leg pain (visual analogue scale, VAS). Association between Modic type and outcomes was explored with a mixed model and then by two-way analysis of variance (ANOVA) at each time point with Modic and treatment groups (surgical, n = 126; nonsurgical, n = 117) as fixed factors, adjusted for disc degeneration, age, sex, smoking, and duration of radicular pain. Modic size was also analyzed using ANOVA. RESULTS: Pain scores had decreased significantly at 1-year follow-up. Modic type was significantly related to McGill sensory scores (mixed model: p = 0.014-0.026; ANOVA: p = 0.007 at 6 weeks), but not to VAS back pain or VAS leg pain scores. At 6 weeks, the mean McGill sensory score was higher in Modic I than in Modic II-III patients (p = 0.003) and in patients without Modic changes (p = 0.018). Modic size L1-S1 was not associated with pain outcomes. CONCLUSION: Patients with lumbar radicular pain have a substantial pain reduction during 1-year follow-up, but Modic type I changes may imply a slower initial decrease in sensory pain.


Assuntos
Deslocamento do Disco Intervertebral/epidemiologia , Deslocamento do Disco Intervertebral/cirurgia , Dor Lombar/epidemiologia , Dor Lombar/cirurgia , Vértebras Lombares/patologia , Radiculopatia/epidemiologia , Radiculopatia/cirurgia , Adulto , Distribuição por Idade , Comorbidade , Feminino , Seguimentos , Humanos , Deslocamento do Disco Intervertebral/diagnóstico , Dor Lombar/diagnóstico , Imagem por Ressonância Magnética/estatística & dados numéricos , Masculino , Noruega/epidemiologia , Medição da Dor/estatística & dados numéricos , Prevalência , Radiculopatia/diagnóstico , Distribuição por Sexo , Estatística como Assunto , Resultado do Tratamento
7.
J Neurosci ; 32(29): 9831-4, 2012 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-22815498

RESUMO

Earlier studies have shown that the single nucleotide polymorphism (SNP) A118G (rs1799971) in the opioid receptor mu 1 (OPRM1) gene may affect pain sensitivity. In the present study we investigated whether the A118G SNP could predict clinical outcome regarding progression of pain intensity and disability in patients with low back pain and sciatica after lumbar disc herniation. Patients (n = 258) with lumbar disc herniation and sciatic pain, all European-Caucasian, were recruited from two hospitals in Norway. Pain and disability were rated on a visual analog scale (VAS), by McGill Sensory Questionnaire and by Oswestry Disability Index (ODI) over a 12 months period. The data revealed a significant interaction between sex and A118G genotype regarding the pain intensity during the 12 months (VAS, p = 0.002; McGill, p = 0.021; ODI, p = 0.205, repeated-measures ANOVA). We found that */G women had a slower recovery rate than the */G men. Actually, the */G women had 2.3 times as much pain as the */G men 12 months after the disc herniation (VAS, p = 0.043, one-way ANOVA; p = 0.035, Tukey HSD). In contrast, the A/A women and A/A men seemed to have almost exactly the same recovery rate. The present data suggest that OPRM1 G allele increases the pain intensity in women, but has a protective effect in men the first year after disc herniation.


Assuntos
Deslocamento do Disco Intervertebral/genética , Dor Lombar/genética , Polimorfismo de Nucleotídeo Único , Receptores Opioides mu/genética , Ciática/genética , Adolescente , Adulto , Alelos , Feminino , Seguimentos , Genótipo , Humanos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/cirurgia , Dor Lombar/etiologia , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Ciática/etiologia , Ciática/cirurgia , Fatores Sexuais , Inquéritos e Questionários
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