7 results on '"Stone, Laura"'
Search Results
2. Differential Deoxyribonucleic Acid Methylation in Painful Versus Non-Painful Degenerating Intervertebral Discs: A Human Case Study
- Author
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Yeater, Taylor D., Lee, Peter, Kawarai, Yuya, and Stone, Laura S.
- Abstract
Chronic back pain poses a significant health concern. Though back pain is often attributed to disc degeneration (DD), intervertebral disc (IVD) degeneration is frequently experienced without pain. Why does DD lead to discogenic LBP in some cases and remain asymptomatic in others? A growing body of evidence suggests epigenetic modifications, such as DNA methylation, contribute to pathological DD. Understanding DNA methylation in discogenic LBP is crucial due to its reversibility, offering a promising therapeutic target. The goal of this study was to identify DNA methylation patterns associated with painful vs. pain-free DD. In a case involving a subject with LBP and DD at multiple IVD levels, a lumbar discogram was performed before surgery to pinpoint the discs causing pain. Despite severe degeneration, one spinal level (L5/S1) scored 0/10 on the discogram while L3/L4 and L4/L5 produced pain reports of 10/10 and 8/10, respectively. Next, DNA was isolated from the nucleus pulposus of discs collected during surgery. Methylation analysis was conducted using Illumina Infinium MethylationEPIC v2.0 BeadChip. SeSAMe pipeline in R determined methylation levels (beta values). After filtering for greater than 20% effect size, 315 gene-associated promoter sites were identified. Pathway enrichment analysis revealed terms related to nerve growth (e.g., TRK receptor binding, substrate adhesion-dependent cell spreading, netrin-1 signaling), as well as immune processes (e.g., neutrophil extravasation, T-cell polarity, CD28 co-stimulation). These findings suggest a potential epigenetic mechanism behind the disconnect between DD and pain; thus, raising the possibility of diagnostic or therapeutic strategies for discerning or treating painful disc degeneration.
- Published
- 2024
- Full Text
- View/download PDF
3. Struck From Behind: Maintaining Quality of Life With Chronic Low Back Pain
- Author
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Lebovits, Allen, Hainline, Brian, Stone, Laura S., Seminowicz, David A., Brunz, James T., Rosenquist, Richard W., and Cowan, Penney
- Published
- 2009
- Full Text
- View/download PDF
4. DNA Methylation in Degenerating Human Intervertebral Discs
- Author
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Lee, Seunghwan, Kawarai, Yuya, Ouellet, Jean, Haglund, Lisbet, Szyf, Moshe, and Stone, Laura S.
- Abstract
Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP) and is associated with widespread changes in gene expression, extracellular matrix (ECM) degradation, inflammation, and innervation. Epigenetic modifications, including DNA methylation, can drive changes in gene expression without modifying DNA sequences. To date, little is known about epigenetic dysregulation in degenerated IVDs. The objective of this study was to investigate changes in DNA methylation in degenerating human IVDs from chronic LBP patients. Human lumbar IVD segments at L4/5 level including control (n=4) and degenerating (n=6) were homogenized in liquid nitrogen with a mortar and pestle and genomic DNA was extracted using the Qiagen DNeasy Blood and Tissue kit. Epigenome-wide 5mC mapping was performed following bisulfite sequencing using the Infinium MethylationEPIC BeadChip 850k Arrays. All analysis was performed in the R package RnBeads 2.0. Principal component analysis and hierarchical clustering analysis revealed group differences between healthy and degenerating IVDs. Pathway analysis revealed enrichment in genes related to ECM organization, signaling by receptor tyrosine kinases and signaling by interleukins. Further analysis at the single gene promoter level showed hypermethylation in ECM-related genes linked to IVD degeneration including sparc and col2a1 and hypomethylation of pro-inflammatory cytokines associated with IVD degeneration including IL-1b and IL-8. These changes in methylation would be expected to result in loss of ECM and increased inflammation. Persistent reprogramming of gene expression by DNA methylation could drive IVD degeneration and inflammation. Understanding the role of DNA methylation in IVD pathology may provide a scientific framework for the development of new therapeutic approaches.
- Published
- 2022
- Full Text
- View/download PDF
5. Sex differences in the serum proteomic profile during acute low back pain โ A preliminary study of the relationship to future low back pain
- Author
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Jenkins, Luke C, Chang, Wei-Ju, Humburg, Peter, Wasinger, Valerie C, Stone, Laura S, Dorsey, Susan G, Renn, Cynthia, Starkweather, Angela, and Schabrun, Siobhan M
- Abstract
The molecular processes driving the transition from acute to chronic low back pain (LBP) remain poorly understood and are likely to be sexually dimorphic. This study aimed to explore sex-differences in the serum proteomic profile of people experiencing an acute LBP episode and determine if serum protein concentrations were associated with three-month outcome. Serum samples were collected through venepuncture from 30 female and 29 male participants experiencing an acute LBP episode. Serum samples underwent trypsin digestion and fractionation using hydrophobic interaction chromatography and were then analysed using mass-spectrometry (MS). MS spectra were searched in the Swissprot database for protein identification. Sex differences in protein abundance changes were evident upon inspection of fold changes. Multivariable data analysis identified 21 serum proteins during the acute episode that correctly classified 93% of males and 23 serum proteins that correctly classified 90% of females with ongoing LBP at three months. Pathway analysis suggested the differentially expressed proteins during acute LBP were frequently involved in immune, inflammatory, complement or coagulation responses. This data provides preliminary evidence that biological processes during an acute LBP episode may contribute to resolution, or persistence, of LBP symptoms at three months, however, these processes differ between males and females.
- Published
- 2023
- Full Text
- View/download PDF
6. Inter- and Trans-generational Inheritance of Paternal Chronic Pain to Male and Female Offspring in Mice
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Millecamps, Magali, Gregoire, Stephanie, and Stone, Laura
- Abstract
Major life events can alter an individual's molecular profile behavior and impact behavior. There is increasing recognition that, in some circumstances, these alterations can be transmitted to offspring through biological (germline) or environmental inheritance. For example, both inter- and trans-generational transmission of stress and trauma have been documented in both humans and rodents. The goal of the present study was to assess inter- and trans-generational inheritance of paternal chronic pain. Nine-month-old CD1 male mice without or with chronic neuropathic pain for 6 months (Sham and Spared Nerve Injury (SNI), respectively) were mated with naïve young CD1 females (F0). Intergenerational inheritance was assessed in their direct progeny (F1) and transgenerational inheritance in further descendants (F2). F2 was generated by mating unrelated females and males from F1 SNI or Sham lineages. Sensitivity to mechanical and cold stimuli were assessed using von Frey filament and acetone tests, respectively. Males and females from F1 and F2 were tested at 2.5 months of age (n=15-70/group). A subset of animals of each sex and generation received intra-plantar CFA (Complete Freud Adjuvant) and were monitored for 3 days (n=11-15/group). No differences between mice from the two lineages were observed in mechanical sensitivity at baseline or in response to CFA. In contrast, F1 females and F2 males from SNI lineages were hypersensitive to cold at baseline compared to sham lineages. Interestingly, F1 females and F2 males from SNI lineages demonstrated weaker behavioral responses to acetone after CFA-injection compared to sham lineages. Paternal experience can influence offspring development. Our results provide evidence that a family history of chronic pain can lead to sex-specific inter- and trans-generational inheritance of cutaneous hypersensitivity. Further studies are required to dissect the mechanisms driving these phenomena. Grant support from Canadian Institutes of Health Research PJT-362909 to LSS.
- Published
- 2022
- Full Text
- View/download PDF
7. Sex Differences in the Serum Proteomic Profile During Acute Low Back Pain-A Preliminary Study of the Relationship to Future Low Back Pain.
- Author
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Jenkins LC, Chang WJ, Humburg P, Wasinger VC, Stone LS, Dorsey SG, Renn C, Starkweather A, and Schabrun SM
- Subjects
- Humans, Female, Male, Adult, Young Adult, Blood Proteins analysis, Middle Aged, Acute Pain blood, Proteome metabolism, Low Back Pain blood, Sex Characteristics, Proteomics
- Abstract
The molecular processes driving the transition from acute to chronic low back pain (LBP) remain poorly understood and are likely to be sexually dimorphic. This study aimed to explore sex differences in the serum proteomic profile of people experiencing an acute LBP episode and determine if serum protein concentrations were associated with three-month outcome. Serum samples were collected through venepuncture from 30 female and 29 male participants experiencing an acute LBP episode. Serum samples underwent trypsin digestion and fractionation using hydrophobic interaction chromatography and were then analysed using mass-spectrometry. Mass-spectrometry spectra were searched in the Swissprot database for protein identification. Sex differences in protein abundance changes were evident upon inspection of fold changes. Multivariable data analysis identified 21 serum proteins during the acute episode that correctly classified 93% of males and 23 serum proteins that correctly classified 90% of females with ongoing LBP at 3 months. Pathway analysis suggested the differentially expressed proteins during acute LBP were frequently involved in immune, inflammatory, complement, or coagulation responses. This data provides preliminary evidence that biological processes during an acute LBP episode may contribute to the resolution, or persistence, of LBP symptoms at 3 months, however, these processes differ between males and females. PERSPECTIVE: Differential expression of serum proteins was observed between male and female participants during an acute LBP episode. This preliminary work provides a foundation for future research targeting distinct immune system processes in males and females that may interfere with the transition from acute to chronic LBP., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
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