Differential expression of cerebrospinal fluid neuroinflammatory mediators depending on osteoarthritis pain phenotype

Abstract

Neuroinflammation is implicated in the development and maintenance of persistent pain states, but there are limited data linking cerebrospinal fluid (CSF) inflammatory mediators with neurophysiological pain processes in humans. In a prospective observational study, CSF inflammatory mediators were compared between patients with osteoarthritis (OA) who were undergoing total hip arthroplasty due to disabling pain symptoms (n = 52) and pain-free comparison controls (n = 30). In OA patients only, detailed clinical examination and quantitative sensory testing were completed. Cerebrospinal fluid samples were analyzed for 10 proinflammatory mediators using Meso Scale Discovery platform. Compared to controls, OA patients had higher CSF levels of interleukin 8 (IL-8) (P = 0.002), intercellular adhesion molecule 1 (P = 0.007), and vascular cell adhesion molecule 1 (P = 0.006). Osteoarthritis patients with central sensitization possibly indicated by arm pressure pain detection threshold <250 kPa showed significantly higher CSF levels of Fms-related tyrosine kinase 1 (Flt-1) (P = 0.044) and interferon gamma-induced protein 10 (IP-10) (P = 0.024), as compared to subjects with PPDT above that threshold. In patients reporting pain numerical rating scale score ≥3/10 during peripheral venous cannulation, Flt-1 was elevated (P = 0.025), and in patients with punctate stimulus wind-up ratio ≥2, CSF monocyte chemoattractant protein 1 was higher (P = 0.011). Multiple logistic regression models showed that increased Flt-1 was associated with central sensitization, assessed by remote-site PPDT and peripheral venous cannulation pain, and monocyte chemoattractant protein-1 with temporal summation in the area of maximum pain. Multiple proinflammatory mediators measured in CSF are associated with persistent hip OA-related pain. Pain phenotype may be influenced by specific CSF neuroinflammatory profiles.

Preoperative sleep quality and adverse pain outcomes after total hip arthroplasty

“…The current research was part of a prospective, observational study (neuroPSI, neuro pain sleep immunology) of patients with disabling OA‐related pain undergoing THA (Bjurström et al., 2020). The study was conducted at a fast‐track, orthopedic surgical center (Hässleholm Hospital).…”

“…The following QST measures were defined as preoperative objective pain outcomes: pressure pain detection threshold (PPDT), pressure pain tolerance threshold (PPTT), and conditioned pain modulation (CPM). We have previously described our QST protocol in detail (Bjurström et al, 2020).…”

Effect of perioperative use of parecoxib on chronic post-surgical pain in elderly patients after hepatectomy: a prospective randomized controlled study

“…Peng et al found in aged rats that parecoxib inhibits hepatectomy-induced IL-1β and TNF-α expression in the hippocampus through the downregulation of the COX-2/PGE2 pathway [ 23 ]. Bjurstrom et al [ 16 ] reported that the proinflammatory mediators in cerebrospinal fluid are associated with persistent post-surgical pain. In clinical trials, due to technical limitations, real-time monitoring of central neuroinflammation is challenging.…”

“…The observational data unpublished from patients after liver surgery revealed a CPSP prevalence of 48.6%. Previous studies [ 16 , 17 ] were used to determine the sample size. Based on an α of 5% and a power of 80%, a sample size of 44 patients per group was sufficient to detect a difference between the parecoxib and placebo groups, given the occurrence rate of 20 and 50%, respectively.…”

Impact of Perioperative Use of Parecoxib on Chronic Postsurgical Pain in Elderly Patients Undergoing Hepatectomy: A Prospective Randomized Controlled Study

“…Peng et al found in aged rats that parecoxib inhibits hepatectomy-induced IL-1β and TNF-αexpression in the hippocampus through downregulation of the COX-2/PGE2 pathway [10]. Bjurstrom et al reported that proin ammatory mediators in cerebrospinal uid are associated with persistent postsurgical pain [18]. In clinical trials, due to technical limitations, real-time monitoring of central neuroin ammation is challenging to achieve.…”