Dataset Information

Implication of microglia activation and CSF-1/CSF-1Rpathway in lumbar disc degeneration-related back pain.

ABSTRACT: Back pain is common and costly. Although lumbar disc degeneration has long been regarded as a major contributor to back pain, how disc degeneration leads to back pain remains unclear. Recent studies observed microglia activation in the spinal cord after disc degeneration, suggesting activated microglia may be involved in discogenic back pain. To determine whether microglia activation participates in disc degeneration-induced back pain, we used a modified disc puncture-induced degeneration-related back pain mouse model to examine the changes in spinal microglia and investigate the potential link between microglia activation and discogenic back pain. In this study, 46 CX3CR1^GFP/+ male mice were used in experimental and sham groups. A modified posterolateral retroperitoneal approach was used to expose the L3/L4 disc to induce the needle puncture in the experimental group. Behavioral tests, including grip force and physical function, were used to measure back pain at pre- and postsurgery. The L3 dorsal root ganglions and lumbar spinal cord were obtained at postoperative weeks 1 to 4 followed by immunofluorescence with different antibodies. Micrographs were obtained by confocal microscopy, and morphometric measurements of microglia were analyzed using Imaris. The punctured disc underwent progressive degeneration and mice with disc degeneration showed impaired grip force and physical function. Compared to the control mice, the number of microglia in the lumbar spinal cord was significantly increased in the disc-punctured animals. Moreover, accumulated microglia exhibited larger soma size and lesser ramification in the disc-injured mice. Immunofluorescence demonstrated colony-stimulating factor 1, a cytokine that promotes microglia repopulation, was significantly increased in L3 dorsal root ganglions, whereas its receptor colony-stimulating factor 1 receptor was upregulated on microglia in the disc-injured mice. In summary, lumbar disc puncture caused progressive disc degeneration which induced microglia activation and back pain in mice. Increased colony-stimulating factor 1/colony-stimulating factor 1 receptor signaling is involved in the disc degeneration-induced microglia activation and back pain.

SUBMITTER: Yang G

PROVIDER: S-EPMC6243401 | biostudies-literature | 2018 Jan-Dec

REPOSITORIES: biostudies-literature

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Implication of microglia activation and CSF-1/CSF-1Rpathway in lumbar disc degeneration-related back pain.

Yang Ge G Chen Lunhao L Gao Zhihua Z Wang Yue Y

Molecular pain 20180101

Back pain is common and costly. Although lumbar disc degeneration has long been regarded as a major contributor to back pain, how disc degeneration leads to back pain remains unclear. Recent studies observed microglia activation in the spinal cord after disc degeneration, suggesting activated microglia may be involved in discogenic back pain. To determine whether microglia activation participates in disc degeneration-induced back pain, we used a modified disc puncture-induced degeneration-relate ...[more]

PMID: 30326776

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Project description:BackgroundAlthough 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.MethodsParticipants 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.ResultsOf 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.ConclusionsLDD 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.

Project description:BackgroundInflammatory and matrix degrading gene variants have been reported to be associated with disc degeneration. Some of these variants also modulate peripheral pain. This study examines the association of these genetic variants with radiographic lumbar disc degeneration and changes in pain and disability at long-term after surgical and cognitive behavioural management.Methods93 unrelated patients with chronic low back pain (CLBP) for duration of >1 year and lumbar disc degeneration were treated with lumbar fusion or cognitive intervention and exercises. Standardised questionnaires included the Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for CLBP, were filled in by patients both at baseline and at 9 years follow-up. Degenerative changes at baseline Magnetic Resonance Imaging and Computed Tomography scans, were graded as moderate and severe (N=79). Yield and quality of blood and saliva DNA was assessed by nano drop spectrophotometry. Eight SNPs in 5 inflammatory and matrix degrading genes were successfully genotyped. Single marker and haplotype association with severity of degeneration, number of discs involved, changes in ODI and VAS CLBP, was done using Haploview, linear regression and R-package Haplostats.ResultsAssociation analysis of individual SNPs revealed association of IL18RAP polymorphism rs1420100 with severe degeneration (p = 0.05) and more than one degenerated disc (p = 0.02). From the same gene two SNPs, rs917997 and rs1420106, were found to be in strong linkage disequilibrium (LD) and were associated with post treatment improvement in disability (p = 0.02). Haplotype association analysis of 5 SNPs spanning across IL18RAP, IL18R1 and IL1A genes revealed significant associations with improvement in disability (p=0.02) and reduction in pain (p=0.04). An association was found between MMP3 polymorphism rs72520913 and improvement in pain (p = 0.03) and with severe degeneration (p = 0.006).ConclusionsThe findings of the current study suggest a role of variation at inflammatory and matrix degrading genes with severity of lumbar disc degeneration, pain and disability.

Dataset Information

Implication of microglia activation and CSF-1/CSF-1Rpathway in lumbar disc degeneration-related back pain.

Publications

Implication of microglia activation and CSF-1/CSF-1Rpathway in lumbar disc degeneration-related back pain.

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