BACKGROUND:Low frequency ultrasound has been proved effective in accelerating the drug permeation across the skin in animals.In this study,the speed and depth of human percutaneous absorption were assessed with drug for local anesthesia mediated by low frequency ultrasound. OBJECTIVE:To determine the effects of low frequency ultrasound on local anesthesia produced by transdermal eutectic mixture of local anesthetics(EMLA) delivery. DESIGN:A double blind randomized controlled trial was conducted. SETTING and PARTICIPANTS:The study was conducted in Qindu Hospital,Fourth Military Medical University.All the subjects were twenty four voluntary students from the university. INTERVENTIONS:The healthy volunteers were included on the basis of inclusion and exclusion criteria.Their forearms were randomly allocated with EMLA plus ultrasound or EMLA alone,matched in each individual.The drug was applied on both arms,with the trial arm exposed to low frequency ultrasound after 10 minutes contact with the drug for 10 minutes,with frequency of 20 kHz and power strength of 0.5 W/cm2. MAIN OUTCOME MEASURES:The pain threshold and pain intensity in the skin were measured every 5 minutes for 2 hours in blinded manner by Transcucer Indication Model 1601C.Histological changes in the skin were determined by anatomic microscopy. RESULTS:The average latency of analgesia was (34.58±3.87) minutes in ultrasound group and (43.75±4.72) minutes in control group,with a significant difference(t=7.62,P< 0.01).No pathological change in the skin was found in ultrasound group. CONCLUSION:Low frequency ultrasound has phonophoresis effect by enhancing topical anesthesia induced by transdermal delivery of EMLA.Ultrasound mediated transdermal delivery of drugs deserves more research and practice.