There is an increasing interest in the use of non-invasive brain stimulation to modulate cortical activity for treating pain and psychiatric disorders. One such method is transcranial Direct Current Stimulation (tDCS) which has a reasonably high safety profile with few side effects and easy to administer. A number of studies reported that it can relieve neuropathic, musculo-skeletal and visceral pain as well as headaches and migraine. High Definition Transcranial Direct Current Stimulation (HD-tDCS) is a refinement of the tDCS method and aims to focus the area of stimulation to a specific brain region. We have tested this technique targeting a novel brain area in a human model of experimental pain. In a sham-controlled single-blinded trial we investigated the effects of HD-tDCS over two cortical targets: the primary motor cortex and the insula in a human model of capsaicin-induced pain.Thirty healthy volunteers (14 female, mean age 32.8 years) were divided into 3 groups and all had capsaicin cream (0.075%) applied for 30 minutes on a 9 cm2 area of skin on the volar surface of both arms. The areas of hyperalgesia after capsaicin application were measured by mapping the areas of primary and secondary hyperalgesia using a brush, a 19 g-Von-Frey Filament, and a calibrated 40 g-pinprick (Neurotips). Ten volunteers in each group then received 20 minutes of anodal HD-tDCS (2 mA) targeting the left primary motor cor-tex, left insular cortex or sham-placebo stimulation. Cortical targeting for stimulation was determined after running com-puter simulated brain conductivity models. Cutaneous areas of hyperalgesia were re-mapped after stimulation. The visual analogue pain scale was repeated throughout the experiment for assessing pain severity.We found a significant reduction in subjective pain scores (VAS) and areas of primary and secondary hyperalgesia after motor or insular cortex HD-tCDS compared to sham stimula-tion. The effects of insula stimulation appear to be bilateral while the reduction in cutaneous hyperalgesia was mainly contralateral to motor cortex HD-tCDS. We found that volun-teers in the stimulation groups also reported a significantly faster reduction in pain scores compared to the sham group. The volunteers failed to differentiate whether they had active or sham stimulation.In a human model of capsaicin-induced pain, anodal HD-tCDS of motor and insula cortex was shown to reduce pain and hyperalgesia compared to sham stimulation. This study shows that it is possible to stimulate the insular cortex using HD tCDS and the effects are bilateral as opposed to motor cortex stim-ulation where reduction in pain and hyperalgesia is predom-inantly contralateral.