The use of high definition transcranial direct current stimulation (HD-tDCS) has shown analgesic effects in some chronic pain patients, but limited anti-nociceptive effects in healthy asymptomatic subjects. This double-blinded sham-controlled study assessed the effects of HD-tDCS applied on three consecutive days on central pain mechanisms in healthy participants with (N=40) and without (N=40) prolonged experimental pain induced by intramuscular injection of nerve growth factor into the right hand on Day1. Participants were randomly assigned to Sham-tDCS (N=20 with pain, N=20 without) or Active-tDCS (N=20 with pain, N=20 without) targeting simultaneously the primary motor cortex and dorsolateral prefrontal cortex for 20 min with 2mA stimulation intensity. Central pain mechanisms were assessed by cuff-algometry on the legs measuring pressure pain sensitivity, temporal summation of pain (TSP) and conditioned pain modulation (CPM), at baseline and after HD-tDCS on Day2 and Day3. Based on subject's assessment of received HD-tDCS (sham or active) they were effectively blinded. Compared with Sham-tDCS, Active-tDCS did not significantly reduce the average NGF-induced pain intensity. Tonic pain-induced temporal summation at Day2 and Day3 was significantly lower in the NGF-pain group under Active-tDCS compared to the pain group with Sham-tDCS (P≤0.05). No significant differences were found in the cuff pressure pain detection/tolerance thresholds or CPM effect across the 3 days of HD-tDCS in any of the four groups. HD-tDCS reduced the facilitation of TSP caused by tonic pain suggesting that efficacy of HD-tDCS might depend on the presence of sensitized central pain mechanisms.