The incidence of chronic postoperative pain after total knee replacement (TKR) is approx. 20%, and hence preoperative risk factors are important to identify. Recent studies have indicated that preoperative inflammatory markers might hold prognostic information for the development of chronic postoperative pain. Long non-coding RNA (lncRNA) regulates the expression of genes related to e.g. inflammatory processes. The current study aimed to investigate the preoperative lncRNA signature as possible preoperative predictive markers for chronic postoperative pain following TKR. Serum samples, collected preoperatively from 20 knee osteoarthritis (KOA) patients, were analyzed for 84 validated circulatory lncRNA. Pain intensity was assessed using a visual analog scale (VAS) before and one-year after TKR. Differences for the lncRNA expression were analyzed between patients with chronic postoperative pain (VAS≥3) and those with a normal postoperative recovery (VAS<3). LncRNA Myeloid Zinc Finger 1 Antisense RNA 1 (MZF1-AS1) (fold change -3.99; p-value: 0.038) (shown to be involved neuropathic pain) Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) (fold change -3.39; p-value: 0.044) (shown to be involved neuropathic pain); Patched 1 pseudogene (LOC100287846) (fold change -6.99; p-value: 0.029) (unknown in pain) were down-regulated preoperatively in the group with chronic postoperative pain compared to the group normal postoperative pain recovery. These findings suggest, that TKR patients with chronic postoperative pain present preoperative downregulations of three specific lncRNA detectable at the systemic level. The presented study might give new insights into the complexity of chronic postoperative pain development and show how non-coding RNA plays a role in the underlying molecular mechanisms of pain. © 2021 Walter de Gruyter GmbH, Berlin/Boston.

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