Objectives. To assess the effects of intra-articular therapy on pain sensitivity in the knee and surrounding tissues in knee OA patients. Methods. Twenty-five knee OA patients with symptomatic knee OA were included in this interventional cohort study. Pressure pain thresholds (PPT) were recorded before, immediately after, and two weeks after ultrasound guided intra-articular injection of lidocaine combined with glucocorticosteroid. Computer-controlled and manual pressure algometers were used to assess PPT on the knee, vastus lateralis, tibialis anterior, and the extensor carpi radialis longus muscles (control site). Results. Significantly increased PPTs were found following intra-articular injection, at both the knee (P < 0.0001) and the surrounding muscles (P < 0.042). The treatment effects were sustained for two weeks, and at some points the effect was even greater at two weeks (P < 0.026). Albeit not statistically significant, a similar trend was observed at the control site. Conclusions. Intra-articular anesthesia, combined with glucocorticosteroid, reduced pain sensitivity in both the knee and surrounding muscles for at least two weeks.