Conditioned pain modulation and temporal summation in patients with knee osteoarthritis: A systematic review and meta-analysis

Abstract

This review aims to determine the current evidence on conditioned pain modulation (CPM) and temporal summation of pain (TSP) in patients with knee osteoarthritis (KOA) compared to healthy pain-free controls. A comprehensive search was conducted across. seven electronic databases (MEDLINE/PubMed, EMBASE, CINAHL, PsycINFO, Cochrane Library, Web of Science, and Scopus) were searched. Studies measuring CPM/TSP in patients with KOA compared to a group of healthy pain-free controls were included. Two reviewers independently determined study eligibility, rated risk of bias and extracted data. Where possible, data were combined into meta-analyses and pooled estimates with 95% confidence intervals (CI) for standardized mean differences (SMD) were calculated. From a total of 1943 papers identified in the initial search, 19 studies were included after screening. Most studies were of moderate to high risk of bias. Very low-certainty evidence suggests lower local CPM efficiency with a moderate effect size (556 patients and 379 controls; SMD =-0.55 [-0.86 to-0.24]; p = 0.00) and higher TSP with a small effect size when assessed both locally (910 patients and 463 controls; SMD = 0.40 [0.21 to 0.58]; p = 0.00) and remotely (468 patients and 231 controls; SMD = 0.27 [0.04 to 0.51]; p = 0.03) in KOA patients compared to pain-free controls. These findings suggest impaired CPM and facilitated TSP in patients with KOA. Clinicians should implement treatment strategies not only directed at nociceptive sources but also aimed at addressing alterations in central pain processing and symptoms related to nociplastic pain. Protocol registration: (CRD42022370869). Perspective: This study highlights the impaired conditioned pain modulation and facilitated temporal summation in knee osteoarthritis patients, suggesting central sensitization. These findings emphasize the need for targeted treatments to address both nociceptive sources and central pain processing alterations.