The role of co-occurring insomnia and mental distress in the association between lumbar disc degeneration and low back pain related disability.

BACKGROUND: Lumbar disc degeneration (LDD) is associated with low back pain (LBP). Although both insomnia and mental distress appear to influence the pain experience, their role in the association between LDD and LBP is uncertain. Our objective was to investigate the role of co-occurring insomnia and mental distress in the association between LDD and LBP-related disability. METHODS: A total of 1080 individuals who had experienced LBP during the previous year underwent 1.5-T lumbar magnetic resonance imaging, responded to questionnaires, and participated in a clinical examination at the age of 47. Full data was available for 843 individuals. The presence of LBP and LBP-related disability (numerical rating scale, range 0-10) were assessed using a questionnaire. LDD was assessed by a Pfirrmann-based sum score (range 0-15, higher values indicating higher LDD). The role of insomnia (according to the five-item Athens Insomnia Scale) and mental distress (according to the Hopkins Symptom Check List-25) in the association between the LDD sum score and LBP-related disability was analyzed using linear regression with adjustments for sex, smoking, body mass index, education, leisure-time physical activity, occupational physical exposure, Modic changes, and disc herniations. RESULTS: A positive association between LDD and LBP-related disability was observed among those with absence of both mental distress and insomnia (adjusted B = 0.132, 95% CI = 0.028-0.236, p = 0.013), and among those with either isolated mental distress (B = 0.345 CI = 0.039-0.650, p = 0.028) or isolated insomnia (B = 0.207, CI = 0.040-0.373, p = 0.015). However, among individuals with co-occurring insomnia and mental distress, the association was not significant (B = -0.093, CI = -0.346-0.161, p = 0.470). CONCLUSIONS: LDD does not associate with LBP-related disability when insomnia and mental distress co-occur. This finding may be useful when planning treatment and rehabilitation that aim to reduce disability among individuals with LDD and LBP. Future prospective research is warranted.

Association of lumbar disc degeneration with low back pain in middle age in the Northern Finland Birth Cohort 1966.

BACKGROUND: Although it has been suggested that lumbar disc degeneration (LDD) is a significant risk factor for low back pain (LBP), its role remains uncertain. Our objective was to clarify the association between LDD and LBP and whether mental distress modifies the association. METHODS: Participants of a birth cohort underwent 1.5-T lumbar magnetic resonance imaging at the age of 47. The association between the sum score of LDD (Pfirrmann classification, range 0-15) and LBP (categorized into "no pain", "mild-to-moderate pain", "bothersome-and-frequent pain") was assessed using logistic regression analysis, with sex, smoking, body mass index, physical activity, occupational exposure, education, and presence of Modic changes and disc herniations as confounders. The modifying role of mental distress (according to the Hopkins Symptom Check List-25 [HSCL-25], the Beck Depression Inventory and the Generalized Anxiety Disorder Scale) in the association was analyzed using linear regression. RESULTS: Of the study population (n = 1505), 15.2% had bothersome and frequent LBP, and 29.0% had no LBP. A higher LDD sum score increased the odds of belonging to the "mild-to-moderate pain" category (adjusted OR corresponding to an increase of one point in the LDD sum score 1.11, 95% CI 1.04-1.18, P = 0.003) and the "bothersome-and-frequent pain" category (adjusted OR 1.20, 95% CI 1.10-1.31, P < 0.001), relative to the "no pain" category. Mental distress significantly modified the association between LDD and LBP, as a linear positive association was consistently observed among individuals without mental distress according to HSCL-25 (adjusted B 0.16, 95% CI 0.07-0.26, P < 0.001), but not among individuals with higher mental distress. CONCLUSIONS: LDD was significantly associated with both mild-to-moderate and bothersome-and-frequent LBP. However, the co-occurrence of mental distress diminished the association between LDD and LBP bothersomeness. Our results strongly suggest that mental symptoms affect the pain experience.

Lack of R-Ras Leads to Increased Vascular Permeability in Ischemic Retinopathy.

PURPOSE: The role of R-Ras in retinal angiogenesis and vascular permeability was evaluated in an oxygen-induced retinopathy (OIR) model using R-Ras knockout (KO) mice and in human diabetic neovascular membranes. METHODS: Mice deficient for R-Ras and their wild-type (WT) littermates were subjected to 75% oxygen from postnatal day 7 (P7) to P12 and then returned to room air. At P17 retinal vascularization was examined from whole mounts, and retinal vascular permeability was studied using Miles assay. Real-time RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of R-Ras in retina during development or in the OIR model. The degree of pericyte coverage and vascular endothelial (VE)-cadherin expression on WT and R-Ras KO retinal blood vessels was quantified using confocal microscopy. The correlation of R-Ras with vascular endothelial growth factor receptor 2 (VEGFR2) and human serum albumin on human proliferative diabetic retinopathy membranes was assessed using immunohistochemistry. RESULTS: In retina, R-Ras expression was mostly restricted to the vasculature. Retinal vessels in the R-Ras KO mice were significantly more permeable than WT controls in the OIR model. A significant reduction in the direct physical contact between pericytes and blood vessel endothelium as well as reduced VE-cadherin immunostaining was found in R-Ras-deficient mice. In human proliferative diabetic retinopathy neovascular membranes, R-Ras expression negatively correlated with increased vascular leakage and expression of VEGFR2, a marker of blood vessel immaturity. CONCLUSIONS: Our results suggest that R-Ras has a role in controlling retinal vessel maturation and stabilization in ischemic retinopathy and provides a potential target for pharmacologic manipulation to treat diabetic retinopathy.