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Central pain dysregulation in knee osteoarthritis reveals the need for treatments targeting both peripheral and nociplastic mechanisms.  

Researchers conducted a study published in June 2025 in the issue of the Journal of Pain to evaluate existing evidence on conditioned pain modulation (CPM) and temporal summation of pain (TSP) in individuals with knee osteoarthritis (KOA) compared to pain-free controls.  

They searched across 7 electronic databases [MEDLINE/PubMed, EMBASE, CINAHL, PsycINFO, Cochrane Library, Web of Science, and Scopus] to identify studies comparing CPM and TSP in individuals with KOA and healthy pain-free controls, 2 independent reviewers assessed study eligibility, evaluated the risk of bias, and extracted relevant data. When feasible, data were pooled into meta-analyses, and standardized mean differences (SMD) with 95% CI were estimated.  

The results showed that out of 1,943 records, 19 studies met the inclusion criteria. Most studies had a moderate to high risk of bias. Very low-certainty evidence indicated reduced local CPM efficiency in individuals with KOA compared to controls, with a moderate effect size (556 patients and 379 controls; SMD = -0.55 [-0.86 to -0.24]; P= 0.00) [SMD = -0.55 [-0.86 to -0.24]; P= 0.00]. The TSP was elevated in KOA  both locally with a small effect size (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) [SMD = 0.40 [0.21 to 0.58]; P= 0.00; SMD = 0.27 [0.04 to 0.51]; P= 0.03].  

Investigators concluded that individuals with KOA exhibited impaired CPM and enhanced TSP. 

Source: jpain.org/article/S1526-5900(25)00691-1/abstract