To address the role of the dorsolateral prefrontal cortex (DLPFC) in pain we used region of interest (ROI) and psychophysical data from a previous PET study where we observed a distinct negative correlation of DLPFC activity with the unpleasantness of capsaicin-induced heat allodynia (Lorenz et al. SFN abstract# 259.8, 2000). We analyzed the modulation that the DLPFC exerts on the connectivity between heat allodynia-specific ROI by computing inter-regional regressions separately for low and high DLPFC activity. We found that medial thalamic connectivity with the midbrain and limbic forebrain changes systematically during heat allodynia, dependent on DLPFC activity. Midbrain-thalamic connectivity was absent during high but marked during low DLPFC activity. In contrast, thalamic connectivity with the anterior insula and orbitofrontal cortex (OFC) was stronger during high compared to low DLPFC activity. Notably, positive correlations of insula and OFC activity with unpleasantness ratings were only present dur...