Objectives:Chronic pain after total knee replacement (TKR) is not uncommon. Preoperative impaired conditioning pain modulation (CPM) has been used to predict chronic postoperative pain. Interestingly, exercises reduce pain sensitivity in patients with knee osteoarthritis (KOA). This pilot study investigated the association between exercise-induced hypoalgesia (EIH) and CPM on post-TKR pain relief.Methods:Before and 6 months post-TKR, 14 patients with chronic KOA performed the cold pressor test on the nonaffected leg and 2 exercise conditions (bicycling and isometric knee extension), randomized and counterbalanced. Before and during the cold pressor test and after exercises test stimuli were applied to extract the pain sensitivity difference: computer-controlled cuff inflation on the affected lower leg until the participants detected the cuff pain threshold (cPPT) and subsequently the cuff pain tolerance (cPTT) and manual pressure pain thresholds (PPTs) at the legs, arm, and shoulder. Clinical pain intensity (numerical rating scale [NRS]) and psychological distress (questionnaires) were assessed.Results:Clinical pain intensity, psychological distress, cPPT, and PPT at the affected leg improved post-TKR compared with pre-TKR (P<0.05). Preoperatively, the CPM and bicycling EIH assessed by the increase in cPTT correlated with reduction in NRS pain scores post-TKR (P<0.05). Improved CPM and EIH responses after TKR were significantly correlated with reduction in NRS pain scores post-TKR (P<0.05).Discussion:In KOA patients, hypoalgesia after cold pressor stimulation and aerobic exercise assessed preoperatively by cuff algometry was associated with pain relief 6 months after TKR. EIH as a novel preoperative screening tool should be further investigated in larger studies.