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

Background and objective: Differences 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.

Methods: Patients 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.

Results: Four 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.

Conclusions: Despite 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.