scholarly journals Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 224
Author(s):  
Elena V. Tchetina ◽  
Kseniya E. Glemba ◽  
Galina A. Markova ◽  
Evgeniy A. Naryshkin ◽  
Elena A. Taskina ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Postoperative Pain ◽  
Joint Replacement ◽  
Peripheral Blood ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Gene Expressions ◽  
Joint Replacement Surgery ◽  
End Stage

Osteoarthritis (OA) pain implies an indication for joint replacement in patients with end-stage OA. However, chronic postoperative pain is observed in 10–40% of patients with OA. Here, we identified genes whose expression in the peripheral blood before surgery could denote the risk of postoperative pain development. We examined the peripheral blood of 26 healthy subjects and 50 patients with end-stage OA prior to joint replacement surgery. Pain was evaluated before surgery using the visual analog scale (VAS) index and neuropathic pain questionnaires, Douleur Neuropathique 4 Questions (DN4) and PainDETECT questionnaires. Functional activity was assessed using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Three and six months after surgery, pain indices according to VAS of 30% and higher were considered. Metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)1 protein levels were measured using ELISA in the peripheral blood mononuclear cells (PBMCs). Total RNA isolated from whole blood was analysed using quantitative real-time RT-PCR for caspase-3, MMP-9, TIMP1, cathepsins K and S, tumour necrosis factor (TNF)α, interleukin (IL)-1β, and cyclooxygenase (COX)-2 gene expression. Seventeen patients reported post-surgical pain. Expression of cathepsins K and S, caspase-3, TIMP1, IL-1β, and TNFα genes before surgery was significantly higher in these patients compared to pain-free patients with OA. Receiver-operating characteristic (ROC) curve analyses confirmed significant associations between these gene expressions and the likelihood of pain development after arthroplasty. High baseline expression of genes associated with extracellular matrix destruction (cathepsins S and K, TIMP1), inflammation (IL-1β, TNFα), and apoptosis (caspase-3) measured in the peripheral blood of patients with end-stage OA before knee arthroplasty might serve as an important biomarker of postoperative pain development.

scholarly journals THU0472 CATHEPSIN S GENE EXPRESSION MEASURED IN THE PERIPHERAL BLOOD OF OSTEOARTHRITIC PATIENTS PRIOR TO SURGERY AS A BIOMARKER OF POST-OPERATIVE PAIN DEVELOPMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 473.2-473
Author(s):  
E. Tchetina ◽  
K. Glemba ◽  
G. Markova ◽  
E. Taskina ◽  
M. Makarov
Keyword(s):  
Gene Expression ◽  
Postoperative Pain ◽  
Joint Replacement ◽  
Peripheral Blood ◽  
Caspase 3 ◽  
Cathepsin S ◽  
Joint Replacement Surgery ◽  
Replacement Surgery ◽  
Post Operative Pain ◽  
End Stage

Background:Osteoarthritis (OA) is a chronic rheumatic disease, which involves pain, limited inflammation, and local destruction of the knee joint. OA pain is a major clinical symptom, which limits working capacity and denotes an important indication for joint replacement in the end-stage OA. In spite of significant number of positive outcomes, chronic postoperative pain represents a major adverse consequence of surgery, which is observed in 10-40% of OA patients. Therefore, identification of patients potentially capable of developing chronic postoperative pain prior to surgery could significantly improve therapy outcome. Recently we hypothesized that genes related to pain sensitization whose expression is upregulated in about 10-40% of the examined end-stage OA patient cohort might be responsible for postoperative pain. Retrospective analysis of gene expression in the peripheral blood of end-stage OA patients before joint replacement surgery revealed that expression of cathepsins S and K, caspase 3, and MMP-9 genes might be associated with postoperative pain development [Ann Rheum Dis,78, suppl 2:A520].Objectives:To examine the validity of our hypothesis in the prospective study.Methods:We examined peripheral blood of 26 healthy volunteers (average age 55±8.3 years old) and 40 end-stage OA patients (average age 56.5±8.9 years old) undergoing joint replacement surgery. Patients were examined before and 6 months after surgery. Pain was assessed prior to surgery using VAS index and neuropathic pain questionnaires DN4 and PainDETECT. Functional activity was evaluated by WOMAC. After surgery pain indices according to VAS of 30% and higher were considered. MMP-9 and caspase 3 protein levels were quantified by ELISA. Total RNA isolated from whole blood was used in expression studies for caspase 3; metalloproteinase (MMP)-9; cathepsins K and S genes. These were performed with quantitative real-time RT-PCR.Results:Out of 40 patients pain complaints were obtained from 9 patients (22,5%) after 6 months’ post-surgery. Prior to surgery all the examined genes were significantly upregulated in the patients who developed post-operative pain compared to healthy controls and those subjects who did not develop pain after surgery. However, no difference in the levels of the examined pain-related and functional indices in patients, who developed pain or not, was noted before surgery. ROC curve analyses confirmed significant associations (p<0.05) between expressions of the examined genes prior to surgery with the likelihood of pain development after surgery. The cut-off values for the examined gene expressions were 11.34 for cathepsin S (sensitivity of 0.89 and specificity of 0.76), 10.11 for caspase 3 (sensitivity of 0.86 and specificity of 0.65), 10.09 for cathepsin K (sensitivity of 0.86 and specificity of 0.78). Moreover, among the examined genes cathepsin S expression was the most informative predictor of postoperative pain development [AUC= 0.857, 95%CI (0.708-1.000)].Conclusion:High cathepsin S gene expression in the peripheral blood of the end-stage OA patients measured prior to joint replacement surgery could serve an important biomarker of post-operative pain development.Disclosure of Interests: :None declared

scholarly journals Characteristics of a Pathogenic Molecular Clone of an End-Stage Serum-Derived Variant of Simian Immunodeficiency Virus (SIVF359)

2001 ◽  
Vol 75 (19) ◽  
pp. 9328-9338 ◽  
Author(s):  
Lennart Holterman ◽  
Rob Dubbes ◽  
James Mullins ◽  
Gerald Learn ◽  
Henk Niphuis ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Molecular Clone ◽  
Immunodeficiency Virus ◽  
End Stage

ABSTRACT End-stage simian immunodeficiency virus (SIV) isolates are suggested to be the most fit of the evolved virulent variants that precipitate the progression to AIDS. To determine if there were common characteristics of end-stage variants which emerge from accelerated cases of AIDS, a molecular clone was derived directly from serum following in vivo selection of a highly virulent SIV isolate obtained by serial end-stage passage in rhesus monkeys (Macaca mulatta). This dominant variant caused a marked cytopathic effect and replicated to very high levels in activated but not resting peripheral blood lymphocytes. Furthermore, although this clone infected but did not replicate to detectable levels in rhesus monocyte-derived macrophages, these cells were able to transmit infection to autologous T cells upon contact. Interestingly, although at low doses this end-stage variant did not use any of the known coreceptors except CCR5, it was able to infect and replicate in human peripheral blood mononuclear cells homozygous for the Δ32 deletion of CCR5, suggesting the use of a novel coreceptor. It represents the first pathogenic molecular clone of SIV derived from viral RNA in serum and provides evidence that not only the genetic but also the biological characteristics acquired by highly fit late-stage disease variants may be distinct in different hosts.

scholarly journals Dysregulation of MS risk genes and pathways at distinct stages of disease

2017 ◽  
Vol 4 (3) ◽  
pp. e337 ◽  
Author(s):  
Sundararajan Srinivasan ◽  
Marco Di Dario ◽  
Alessandra Russo ◽  
Ramesh Menon ◽  
Elena Brini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Gene List ◽  
Literature Mining ◽  
Specific Gene ◽  
Healthy Population ◽  
Gene Expressions ◽  
Altered Expression ◽  
Risk Genes

Objective:To perform systematic transcriptomic analysis of multiple sclerosis (MS) risk genes in peripheral blood mononuclear cells (PBMCs) of subjects with distinct MS stages and describe the pathways characterized by dysregulated gene expressions.Methods:We monitored gene expression levels in PBMCs from 3 independent cohorts for a total of 297 cases (including clinically isolated syndromes (CIS), relapsing-remitting MS, primary and secondary progressive MS) and 96 healthy controls by distinct microarray platforms and quantitative PCR. Differential expression and pathway analyses for distinct MS stages were defined and validated by literature mining.Results:Genes located in the vicinity of MS risk variants displayed altered expression in peripheral blood at distinct stages of MS compared with the healthy population. The frequency of dysregulation was significantly higher than expected in CIS and progressive forms of MS. Pathway analysis for each MS stage–specific gene list showed that dysregulated genes contributed to pathogenic processes with scientific evidence in MS.Conclusions:Systematic gene expression analysis in PBMCs highlighted selective dysregulation of MS susceptibility genes playing a role in novel and well-known pathogenic pathways.

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