Several imaging techniques have identified different brain areas involved in the processing of noxious stimulation and thus in the constitution of pain. However, only little is known how these brain areas communicate with one another and which areas directionally affect or modulate the activity of succeeding areas. The Granger Causality index (GCI) represents one measure for the analysis of such interactions. In applying time varying bivariate and partial variants of GCI (tvGCI), the aim of the present study was to investigate the interaction of neural activities between a set of scalp electrodes that best represent the brain electrical neural activity of major cortical areas involved in the processing of noxious laser heat stimuli and their variation in time. Bivariate and partial tvGCIs were calculated within different intervals of laser-evoked event-related potentials (LEPs) including a baseline period prior to stimulus application and three intervals immediately following stimulus application, i.e., between 170 and 200 ms (at the N2 component), between 260 ms and 320 ms (P2 component), and between 320 and 400 ms (P3 component of LEPs). Results show some similarities, but also some striking differences between bivariate and partial tvGCIs. These differences might be explained by the nature of bivariate and partial tvGCIs. However, both tvGCI approaches revealed a directed interaction between medial and lateral electrodes of the centroparietal region. This result was interpreted as a directed interaction between the anterior cingulate cortex and the secondary somatosensory cortex and the insula, structures that are significantly involved in the constitution of pain.