RNA expression preoperatively and postoperatively following total knee replacement: a pilot study in patients with and without chronic postsurgical pain

Abstract

Background and objectiveDifferences in gene expression may provide insight into the biological pathways involved in chronic postsurgical pain (CPSP). We compared blood RNA microarrays preoperatively and postoperatively following total knee arthroplasty (TKA) in patients with and without CPSP.MethodsPatients scheduled for primary TKA had whole blood samples obtained preoperatively and at 48 hours and 6 months postsurgery. RNA expression (54 613 transcripts) were assayed using the “Affymetrix HG-U133 plus 2.0” microarray. Genes that met the threshold criteria of ±1.5-fold differential change in expression (CPSP vs non-CPSP), with p<0.0125, were considered for pathway analysis. WikiPathways was used to identify biological pathways that were affected (p<0.01) by differentially regulated genes.ResultsFour of 16 (25%) patients had CPSP at 6 months. Preoperatively, 325 (0.6%) genes met the criteria, with 292 (89.9%) having greater expression in the CPSP group. Twelve biological pathways were affected, with the mitogen-activated kinase, phosphatidylinositide 3-kinase–protein kinase B–mammalian target of rapamycin, and brain-derived neurotrophic factor signaling pathways having known association with pain. At 48 hours, 26 genes met the criteria; 7 pathways were affected, including transforming growth factor-β with known association with pain. At 6 months 55 genes met the criteria, with 49 increased in the CPSP group. Four biological pathways were affected, with only the chemokine signaling pathway having known association with pain.ConclusionsDespite a lack of clinical differences, patients who develop CPSP have upregulated pain pathways preoperatively; however, only the chemokine pathway remained differentially upregulated at 6 months postsurgery.

Effect of 24 mg dexamethasone preoperatively on surgical stress, pain and recovery in robotic-assisted laparoscopic hysterectomy

“…Surgical recovery showed strong correllations with signaling responses in multiple cells, most predominantly in CD14 + monocytes [ 27 ]. Other temporal studies demonstrated mRNA expression in preoperative and postoperative blood samples associated with development of chronic pain after surgery [ 28 ].…”

Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study

“…General responses to surgical and accidental trauma are well described 30 , 31 . Three recent studies, including our own, used targeted approaches and association with surgical outcomes to show changes in cytokine profiles and gene expression following TKA 9 , 14 , 15 . In the current study, using transcriptomics analyses in purified PBCMs and whole blood, we showed that TKA surgery leads to pronounced transcriptional changes in peripheral blood within 24 h, consistent with the previously described responses to trauma 30 – 32 and the changes described in patients recovering from total hip arthroplasty 13 .…”

“…Using whole blood samples collected within 72 h after surgery, Gaudillière et al identified correlations between signaling responses in CD14+ monocyte subsets with recovery from hip surgery 13 . Microarray analyses in blood samples collected before and after surgery identified changes in gene expression associated with the development of persistent pain after TKA 14 . Using serum and synovial fluid samples from patients undergoing TKA, we recently reported a distinct cytokine profile in patients who developed stiffness early after TKA 9 , and we were able to correlate perioperative cytokine levels with persistent postoperative pain after TKA 15 .…”