AbstractBackgroundElectrical stimulation used for brain mapping in the postero‐superior insula can evoke pain. The effects of prolonged high frequency insular stimulation on pain thresholds are unknown.Objective/HypothesisProlonged high frequency insular stimulation, by virtue of its inhibitory properties on networks, could decrease thermal nociception.MethodsEpileptic subjects had electrodes implanted in the insular cortex for the purpose of epileptic focus resection. Thermal and pressure nociceptive thresholds were tested bilaterally on the forearm on two consecutive days. Randomly assigned double‐blind high frequency (150 Hz) insular stimulation took place for 10 min before pain testing either on the first day or on the second day.ResultsSix subjects (three females; mean age of 35 years) were included. Insular stimulation increased heat pain threshold on the ipsilateral (p = 0.003; n = 6) and contralateral sides (p = 0.047; n = 6). Differences in cold pain threshold did not reach statistical significance (ipsilateral: p = 0.341, contralateral: p = 0.143; n = 6), but one subject had a profound decrease in both heat and cold pain responses. Pressure pain threshold was not modified by insular stimulation (ipsilateral: p = 0.1123; contralateral: p = 0.1192; n = 6). Two of the three subjects who had a postero‐superior operculo‐insulectomy developed central pain with contralateral thermal nociceptive deficit.ConclusionsHigh frequency inhibitory postero‐superior insular stimulation may have the potential to decrease thermal nociception. Together with previous studies, our data support the notion that the integrity of this brain region is necessary for thermal but not pressure nociceptive processing.