In a randomized, double-blinded, placebo controlled trial, we investigated the postoperative analgesic effect of a single intra-articular injection of 40 mg methylprednisolone acetate (MP) administered one week prior to total knee arthroplasty (TKA). Forty-eight patients with high pain osteoarthritis (≥ 5 NRS during walk) and sensitization (pressure pain threshold < 250 kPa), aged 50 to 80 years and scheduled for primary unilateral TKA under spinal anaesthesia were included. The primary outcome was the proportion of patient with moderate/severe pain during a 5 meter walk test 24 hours postoperatively. Secondary outcomes included pain at 48 hours, during the first 14 days, sensitization (quantitative sensory testing with pressure pain threshold and wind up from temporal summation) and inflammatory changes (systemic CRP, intra-articular IL-6). No difference in proportion of patients with moderate/severe pain was found between MP/placebo groups at 24 hours (67% and 74%, χ(2)=0.2, p=0.63, odds ratio 0.7, 95% CI 0.2 to 2.8) or at 48 hours (57% and 68%, χ(2)=0.5, p=0.46, odds ratio 0.6 95% CI 0.2 to 2.3), and no difference between groups in postoperative sensitization was found (p > 0.4) despite reduced preoperative intra-articular inflammation (IL-6) in the MP group vs. placebo (median change in IL6: -70 pg/mL [IQR -466 to 0] vs. +32 pg/ml [IQR -26 to 75], p= 0.029). Alternative central or peripheral analgesic interventions in this high-risk group are required.