Prognostic factors for recovery in radicular pain caused by lumbar disc herniation

Lumbar radicular pain constitutes only 5%-10% of low back pain conditions, but it accounts for 33% of the sick leave and 47% of the disability benefits due to back pain in Norway. Previous data show that the recovery from lumbar radicular pain may be influenced by physical, psychosocial, surgery-related and clinical factors. In addition, genetic factors can influence on the development of disc degeneration and the recovery after symptomatic disc herniation. The fact that inflammation contributes to the pathogenesis of disc herniation and radicular pain is now well established. The inflammatory response, initiated from the annulus fibrosus in case of disc herniation, may lead to increased levels of pro-inflammatory interleukins (ILs) close to nerve roots. This inflammatory process could also promote Modic changes. In this thesis, the role of such cytokines and genetic factors in recovery from lumbar radicular pain was addressed. The present data demonstrated a significant association between the inflammatory serum cytokine IL-6 and functional recovery from symptomatic disc herniation. Moreover, the genotype IL-1a C>T rs1800587 increased the risk of persistent pain 1-year after disc herniation. Regarding the radiological factors, we showed that type I Modic changes influences the short-term clinical outcome in patients with low back pain and radicular pain. A sex dependent effect of the opioid receptor mu 1 (OPRM1 A118G) rs1799971 genotype on recovery after disc herniation was also identified. It is concluded that inflammatory, radiological and genetic factors may be important for the recovery after lumbar disc herniation

Subjective health complaints in patients with lumbar radicular pain and disc herniation are associated with a sex - OPRM1 A118G polymorphism interaction: a prospective 1-year observational study

Background Earlier observations show that development of persistent pain may be associated with the genetic variability in the gene encoding for the μ-opioid receptor 1, the OPRM1 A118G (rs1799971). The aim of this study was to investigate the association between OPRM1 genotype and subjective health complaints in patients with radicular pain and disc herniation. Methods A prospective, 1-year observational study was conducted at a hospital back clinic, including 118 Caucasian patients with lumbar radicular pain and MRI confirmed disc herniation. Single nucleotide polymorphism genotyping regarding the OPRM1 A118G was performed. The data of individuals with AA versus AG or GG were analysed separately by linear mixed models. The Subjective Health Complaints Inventory (0-81) including 27 common complaints experienced the previous month on a scale from not at all (0) to severe (3) was used as outcome. Pain, prior duration of leg pain, age, smoking status, and lumbar disc surgery were considered as covariates. Results In total 23 of 118 patients were carriers of the OPRM1 G-allele. All patients except female carriers of the G-allele reported a decrease in pain from baseline to 1 year. Female carriers of the G-allele reported significantly higher subjective health complaints score during the study time span than male carriers of the G-allele when controlling for pain and pain duration. Conclusion The present data indicate that, when controlling for pain intensity and duration, subjective health complaints are associated with a sex - OPRM1 A118G polymorphism interaction in patients with radicular pain

Persistent lumbar radicular and low back pain; impact of genetic variability versus emotional distress

Objective Earlier studies documenting the effect of candidate genes on recovery have seldom taken into consideration the impact of emotional distress. Thus, we aimed to assess the modifying effect of emotional distress on genetic variability as a predictor for pain recovery in lumbar radicular (LRP) and low back pain (LBP). Results The study population comprised 201 patients and mean age was 41.7 years. The significant association between MMP9 rs17576 (B = 0.71, 95% CI 0.18 to 1.24, p = 0.009) and pain recovery remained statistically significant after adjusting for pain intensity at baseline, age, gender, smoking, body mass index, pain localization and emotional distress (B = 0.68, 95% CI 0.18 to 1.18, p = 0.008). In contrast, the association between OPRM1 (B = − 0.85, 95% CI − 1.66 to − 0.05, p = 0.038) and pain recovery was abolished in the multivariate analysis (B = − 0.72, 95% CI − 1.46 to 0.02, p = 0.058). Hence, MMP9 rs17576 and emotional distress independently seem to predict persistent back pain. The predictive effect of OPRM1 rs179971 with regard to the same outcome is probably dependent on other factors including emotional processing. Trial registration The Regional Committee for Medical Research and Ethics reference number 2014/175

Role of IL1A rs1800587, IL1B rs1143627 and IL1RN rs2234677 genotype regarding development of chronic lumbar radicular pain; a prospective one-year study.

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

The time course of clinical outcome measures following disc herniation.

<p>A) and B) patients grouped by <i>IL1A</i> C/T and <i>IL1RN</i> G/A genotypes. VAS activity score (<i>p</i> = 0.049 rmANOVA; <i>p</i> = 0.003 one-way ANOVA at 12 months), ODI score (<i>p</i> = 0.059 rmANOVA; <i>p</i> = 0.050 one-way ANOVA at 12 months). C) and D) patients grouped by <i>IL1B</i> T/C and <i>IL1RN G/A</i> genotypes. VAS activity score (<i>p</i> = 0.175 rm ANOVA; <i>p</i> = 0.105 one-way ANOVA at 12 months), ODI score (<i>p</i> = 0.055 rmANOVA; <i>p</i> = 0.214 one-way ANOVA at 12 months). Data are shown as means ± SEM.</p

Characteristics of patients grouped by the <i>IL1A</i>/<i>IL1B</i> and <i>IL1RN</i> genotypes.

<p>Min, minimum; max, maximum.</p><p>Characteristics of patients grouped by the <i>IL1A</i>/<i>IL1B</i> and <i>IL1RN</i> genotypes.</p

Significance of covariates.

<p>The table gives an overview between covariates and the three outcome measures: VAS and ODI. Covariates with a <i>p</i> value≤0.1 were included in the final model.</p><p>Significance of covariates.</p

Pain- and disability ratings at 12 months.

<p>The table shows the 12 months VAS and ODI scores for the patients grouped by the combinations of <i>IL1A</i> C/T, <i>IL1B</i> T/C and <i>IL1RN</i> G/A genotypes. Mean ± SEM values are shown.</p><p>Pain- and disability ratings at 12 months.</p

Track analysis of the species of Agrodes and Plochionocerus (Coleoptera: Staphylinidae)

The geographical distributions of 2 species of Agrodes and 13 species of Plochionocerus were analyzed using a panbiogeographic approach to identify their biogeographic patterns. Nine species have been recorded as being exclusively freom South America, 2 exclusively freom Central America, and 4 are shared between both areas. Two species of Agrodes and 3 of Plochionocerus are widely distributed in 2 or more subregions of the Neotropical region, and 6 species of Plochionocerus have more restricted distributions, basically ranging in a single subregion, and 4 species are restricted to a small number of localities. Three generalized tracks were identified in the Mesoamerican dominion of the Caribbean subregion, in the northwestern South American dominion of the Caribbean subregion, and in the Amazonian subregion. Species of other staphylinid genera provide additional support to these tracks