Objective

Modic changes (MC), a form of intervertebral disc degeneration visible as subchondral and vertebral bone marrow changes on spine magnetic resonance (MR), are known to be associated with low back pain. This study aimed to identify genes contributing to the development of MC using genome-wide association study.

Background and purpose of study:

Modic change (MC) describes vertebral endplate and bone marrow lesions visible on MRI. MC has been associated with disc degeneration (DD). Independent association of MC with low back pain (LBP) is unclear. The objectives of this study were to assess the relationship between MC and severe, disabling LBP; prevalence and features of DD and incident MC during 10-year follow-up.

Purpose

By systematic literature review, to quantify the association between vertebral endplate signal changes (VESC) and non-specific low back pain (NSLBP).

Introduction: Previous studies have reported controversial associations between exercise and neck or shoulder pains in adolescents. In this study we evaluated the relationships between physical activity or sedentary activities and neck or occipital pain (NOP) or shoulder pain (SP) in a representative sample of adolescents.

Methods: The study population consisted of adolescents belonging to the Northern Finland Birth Cohort 1986 (n=5993). Associations of physical activity level, total sitting time, and different kinds of sedentary activities with NOP and SP were analyzed at 15–16 years of age using logistic regression. “Reporting NOP and SP” (not seeking medical help) and “Consultation for NOP and SP” were assessed separately in girls, but were combined in boys because of low prevalence of “Consultations”.

Results: Almost half of the girls and one third of the boys reported NOP or SP, and 5% of girls and 2% of boys reported “Consultation for NOP or SP” during the past six months. High level of physical activity associated with increased prevalence of both “Consultation for NOP” and “Consultation for SP” in girls, but not in boys. Prolonged sitting was associated with high prevalence of NOP and SP in girls, and NOP in boys. Of various sedentary activities, TV watching and reading books associated with NOP in girls, whereas playing or working with a computer associated with NOP in boys. In girls, TV watching also associated with “Reporting SP”.

Discussion: Both prolonged sitting and high level of physical activity seem to be related to NOP and SP among adolescents.

Aims: Both clinical and epidemiologic studies have shown an association between atherosclerotic changes in the aorta or lumbar arteries and lumbar disc degeneration. However, the association between atherosclerosis and sciatica is unknown. The aim of this study was to investigate the association between carotid intima-media thickness (IMT) and clinically defined sciatica in a representative population sample.

Methods: The target population consisted of people aged 45–74 years who had participated in a nationwide Finnish population study during 2000–2001 and lived within 200 kilometres from the six study clinics. Of the 1867 eligible subjects, 1386 (74%) were included in the study. High-resolution B-mode ultrasound imaging was used to measure IMT. Local or radiating low back pain (LBP) was determined by a standard interview and clinical signs of sciatica by physician’s clinical examination.

Results: Carotid IMT was associated with continuous radiating LBP and with a positive unilateral clinical sign of sciatica. The associations were seen only in men; after adjustment for potential confounders, each standard deviation (0.23 mm) increment in carotid IMT showed an odds ratio of 1.6 (95% confidence interval 1.1–2.3) for continuous radiating LBP and 1.7 (95% confidence interval 1.3–2.1) for a positive unilateral clinical sign of sciatica. This latter association was observed in subjects with and in those without exposure to physical work load factors. Carotid IMT was not associated with local LBP.

Conclusions: Sciatica may be a manifestation of atherosclerosis, or both conditions may share common risk factors.

Introduction: Both physical activity and inactivity have been suggested as risk factors for LBP, but the current evidence is conflicting. In this study we evaluated how the level of leisure time physical activity and amount of sitting are associated with LBP in a general population of adolescents.

Methods: The study population consisted of 5999 boy and girl members of the Northern Finland 1986 Birth Cohort who responded to mailed questions at the age of 15–16 years. LBP during the past six months was classified as “No LBP”, “Reporting LBP” (not seeking medical help), or “Consultation for LBP”. Odds ratios and 95% confidence intervals obtained by multinomial logistic regression were adjusted for smoking and BMI.

Results: Being physically very active (more than six hours of brisk physical activity per week) was associated with increased prevalence of “Consultation for LBP” in both genders, and with “Reporting LBP” in girls, compared to being moderately active (2–3 hours of brisk physical activity per week). High amount of sitting associated with “Consultation for LBP” and “Reporting LBP” in girls, but not in boys.

Discussion: Very active participation in physical activities in both genders and high amount of sitting in girls, irrespective of the level of physical activity, were associated with reported LBP. Perhaps encouraging adolescents to physically moderately active lifestyle could diminish LBP. In addition, avoiding excessive sitting-based activities such as television watching and playing video games may be recommendable among girls.

Introduction: Only few studies have investigated the role of sleep disturbances in adolescents’ musculoskeletal pains.

Methods: A two-year follow-up by postal questionnaires was made for the Northern Finland Birth Cohort 1986 at the ages of 16 and 18 years (n=1773). The outcome measures were six-month period prevalences of self-reported neck pain (NP) and low back pain (LBP) (“Reporting Pain” and “Consultation for Pain”). Sleep disturbances were categorised into three groups (major, minor and no sleep disturbances) based on average hours spent sleeping, and whether or not the subject suffered from nightmares, tiredness and sleeping problems. The odds ratios (OR) and 95% confidence intervals (CI) for were obtained from logistic regression and adjusted for all previously suggested risk factors.

Results: Sleep disturbances at 16 years predicted NP and LBP at the age of 18. Among the adolescents initially without LBP, major sleep disturbances at 16 predicted LBP at 18 in both girls (OR 2.6; 95% CI 1.2 to 5.5) and boys (2.7; 1.1 to 6.7). Similarly, among those initially without NP, major sleep disturbances at 16 years predicted NP at 18 years in girls (3.9; 1.6 to 9.4) but not in boys.

Discussion: Sleep disturbances were an independent risk factor for LBP and NP in adolescence. Possible mechanisms may include decreased time for muscle relaxation during disturbed sleep, co-morbidity with psychological distress, or activation of inflammatory mediators. Perhaps some musculoskeletal pains could be prevented – at least partially – by ensuring that adolescents have sufficient quality and quantity of sleep.

Introduction: Modic changes are vertebral endplate changes visible in magnetic resonance imaging (MRI), which associate with degenerative intervertebral disc disease. Twin studies suggest that intervertebral disc degeneration and low back pain may be primarily explained by genetic factors. There are, however, no studies on genetic factors in Modic changes.

Materials and methods: Eleven variations in eight genes (COL9A2, COL9A3, COL11A2, IL1A, IL1B, IL6, MMP-3 and VDR) were genotyped in an occupational cohort of 159 male train engineers and 69 male paper mill workers. All the study subjects were MRI scanned and evaluated for Modic changes.

Results: Out of 228 subjects studied, 128 (56%) were found to have Modic change at one or more disc levels. 15% of them had exclusively Modic type I while 32% had exclusively Modic II changes. 10% of the subjects had both type I and type II changes. When single nucleotide polymorphisms (SNPs) were analyzed independently, none of them significantly associated with Modic changes. However, when the gene-gene interactions were evaluated IL1A and MMP-3 polymorphisms together associated with type II Modic changes (OR 3.2, 95% CI 1.2–8.5; p = 0.038). Furthermore, IL-1 gene cluster together with MMP-3 polymorphism associated significantly with type II Modic changes (OR = 8.14, 95% CI 1.72–38.44; p = 0.008).

Discussion: This is the first study evaluating the role of genetic factors in relation to Modic changes. Genetic variations in IL-1 cluster and MMP-3 gene were found together to associate significantly with type II Modic changes.

Purpose: The aim of this study was to investigate whether distress alone or in combination with personality traits associates with low back pain (LBP) in adolescence.

Materials and methods: Oulu Back Study (OBS) is a sub-cohort of the Northern Finland 1986 Birth Cohort. Data was collected at 16 and 18 years. The response rate was 69% (1987/2969). Incident cases reported LBP at 18 but not at 16, whereas persistent cases reported back pain at both time points. Distress (GHQ-12) and personality traits (hostility, optimism-pessimism, trait anxiety) were inquired at 18. Logistic regression analysis, stratified for gender, with adjustment for BMI, physical activity, smoking, parents’ socioeconomic status, sedentary hours, and sleep disturbances at 16 years was used. Additionally, the psychological determinants were mutually adjusted in the final analysis.

Results: Distress was associated independently with incident LBP among boys (highest quartile vs. lowest: OR 2.47; 95% CI 1.17–5.21), whereas none of the psychological determinants were significant in incident pain among girls. Trait anxiety was associated with persistent LBP among girls (OR 2.27; 1.09–4.75), and of borderline significance with boys’ persistent pain (OR 2.40; 0.99–5.84). The combination of trait anxiety and distress (highest quartiles) associated significantly with both incident and persistent pain in both genders (OR range from 1.95 to 2.36), whereas of the other combinations of distress with personality traits only pessimism associated with persistent LBP among boys (OR 2.05).

Conclusions: Perceived distress and trait anxiety, alone and especially combined with each other, associate with self-reported LBP in adolescence.

Introduction: We have shown that an IL6 haplotype (GGGA) associates with intervertebral disc disease (IDD) characterized by sciatica. However, its prognostic value for IDD is not known.

Materials and methods: DNA from 153 sciatica patients, who participated in a randomized controlled trial of periradicular infiltration, was analyzed for IL6 variations: c.1–597G> A, c.1–572G> C, c.1–174G> C, and c.486T> A (Genebank #NM_000600.1). Patients recorded back and leg pain intensity and duration (number of days with pain), Oswestry disability, and back-related sick leaves. Repeated measures ANCOVA with adjustment for age, gender and physical work load was used. Square root transformations of outcome data at one, two and three years after the intervention were used for skewed variables.

Results: The prevalence of the GGGA haplotype was 9% (14/153). Data was available from 10 (sick leaves) to 13 (VAS) subjects with and from 107 to 124 subjects without the haplotype. The groups did not differ with respect to pain intensities, or disability. Days with back and leg pain and sick leaves were significantly higher among subjects with the IL6 haplotype (p=0.024, 0.002 and 0.022, respectively). An interaction of the IL6 haplotype and physical work load was significant for duration of back and leg pain and sick leaves (p=0.010, 0.004 and 0.018, respectively).

Discussion: This is the first observation of any prognostic genotype among sciatica patients. The IL6 haplotype GGGA predicted the number of days with back or leg pain, and sickness absence. Subjects with the IL6 haplotype may be more vulnerable when exposed to physically demanding job.

Aims: To evaluate the efþcacy and safety of inßiximab, a monoclonal chimeric antibody against TNFα, for the treatment of severe sciatica. Background: Evidence from animal studies indicates that tumour necrosis factor (TNF)α plays a role in the pathophysiology of sciatica. Anti-TNFα therapy has not been previously evaluated in sciatic patients. Methods: 10 patients with disc herniation-induced severe sciatica received inßiximab (Remi-cade¨; 3mg/weight-kg) intravenously over 2 hours. The outcome was assessed at 1 hour, 1 week, 2 weeks, 1 month and 3 months after the infusion, and was compared to historical controls consisting of 62 patients who received saline in a trial of periradicular inþltration for sciatica. Leg pain was the primary outcome, with over 75% decrease from baseline score constituting a painless state. Fisherñs exact test and repeated measures analysis of variance were used for statistical analysis. Results: One hour after the infusion, leg pain had decreased by 50%. At 2 weeks, 60% of patients in the inßiximab group were painless vs. 16% of control patients (P = 0.006). The difference was sustained at 3-months (90% vs. 46%; P = 0.014). Inßiximab was superior over the whole follow-up period in leg pain (P=0.003) and back-related disability (P=0.004). At 1 month, every patient in the inßiximab group had returned to work whereas 38% of controls were still on sick leave (P=0.02). None of the patients treated with inßiximab underwent surgery during the follow-up. No immediate or delayed adverse drug reactions, or any adverse effects due to medication were observed. Conclusions: Anti-TNFα therapy is a promising treatment option for sciatica. There is an urgent need for a ran-domised controlled trial to evaluate if these promising early results can be conþrmed.

Introduction: Infliximab, a monoclonal antibody against tumour necrosis factor alfa (TNFα) has been used succesfully in the treatment of rheumatoid arthritis and Crohn’s disease. Recent animal studies suggest that TNFα also has an important role in the pathogenesis of sciatica. The purpose of this study was to evaluate the efficacy and safety of infliximab in the treatment of sciatic patients.

Methods: 10 patients with acute or subacute severe sciatica (duration of symptoms from 2 to 12 weeks) were included. A disc herniation corresponding to symptoms was confirmed by MRI in each case. Patients with previous back operation or with contraindications for infliximab were excluded. A dose of 3 mg/kg body weight of infliximab in saline was infused intravenously over 2 hours. Leg pain (100-mm Visual Analog Scale) was recorded before and one hour after the infusion, and later at 1 week, 2 weeks, 1 month, 3 months and 6 months. Changes in leg pain were compared statistically with 62 historical controls (saline group in a study of periradicular infiltration) using repeated measures analysis of variance. Changes in back pain, back-related disability on Oswestry Index and clinical status were also assessed.

Results: Mean (SD) leg pain before the infusion was 80 (18) mm in the infliximab group. One hour after the infusion, there was a decrease of 49% in leg pain. At 1 week mean leg pain was 26 (21), at 2 weeks 19 (20), at 1 month 18 (19), at 3 months 10 (16) and at 6 months 13 (8). When compared with the historical controls, the difference was in favour of infliximab for leg pain (19 mm; 95% CI, 6 to 32, P=0.005) and for back-related disability on Oswestry (12%; 95%CI, 4 to 20, P=0.003) over the 6 month follow-up period. At the one-month follow-up every patient in the infliximab group had returned to work compared to 38% of control patients (P=0.02). None of the patients treated with infliximab underwent surgery during the follow-up compared to 14 (23%) in the control group (P=0.09). No immediate or delayed adverse drug reactions were observed.

Conclusions: According to this study, a single infusion of infliximab seems to provide immediate, highly effective and safe treatment of sciatica through 6 months. Rapid return to work appears to be fascilitated, and surgery may possibly be avoided in some patients. There is an urgent need for a randomized trial to verify these results.