BACKGROUND: Principles of brain plasticity is used in the treatment of patients with functional limitations to improve sensorimotor function. Training is included in the treatment of knee injury to improve both patient-reported function and sensorimotor function. However, impairment in sensorimotor function often persists despite training. Therefore, it was suggested that training programs need to be more effective to improve sensorimotor function after knee injury. The aim of the current study was to investigate if principles of brain plasticity that have been successfully used on the hand and foot to improve sensorimotor function can be applied on the knee. We hypothesized that temporary anesthesia of the skin area above and below the knee would improve sensorimotor function of the ipsilateral knee and leg. METHODS: In this first double-blind exploratory study, 28 uninjured subjects (mean age 26 years, range 19-34, 50% women) were randomized to temporary local cutaneous application of anesthetic (EMLA) (n = 14) or placebo cream (n = 14). Fifty grams of EMLA, or placebo, was applied on the leg 10 cm above and 10 cm below the center of patella, leaving the area around the knee without cream. Measures of sensory function (perception of touch, vibration sense, knee kinesthesia) and motor function (knee muscle strength, hop test) were assessed before and after 90 minutes of treatment with EMLA or placebo. The paired t-test was used for comparisons within groups and the independent t-test for comparisons between groups. The number of subjects needed was determined by an a priori sample size calculation. RESULTS: No statistically significant or clinically relevant differences were seen over time (before vs. after) in the measures of sensory or motor functions in the EMLA group or in the placebo group. There were no differences between the groups due to treatment effect (EMLA vs. placebo). CONCLUSION: We found no effect of temporary cutaneous anesthesia on sensorimotor function of the ipsilateral knee and leg in uninjured subjects. The principles used in this study remain to be tested in subjects with knee injury.