Anxious anticipation and pain: the influence of instructed vs conditioned threat on pain.

Negative emotions such as anxiety enhance pain perception. However, certain threat characteristics are discussed to have different or even divergent effects on pain (hypoalgesia vs hyperalgesia). In order to investigate the neurobiological basis of different threats, we compared the impact of conditioned threat (CT) vs instructed threat (IT) on pain using fMRI. In two groups, participants underwent either Pavlovian threat conditioning or an instructed threat procedure. Afterwards, in an identical test phase participants watched the same visual cues from the previous phase indicating potential threat or safety, and received painful thermal stimulation. In the test phase, pain ratings were increased in both groups under threat. Group comparisons show elevated responses in amygdala and hippocampus for pain under threat in the CT group, and higher activation of the mid-cingulate gyrus (MCC) in the IT group. Psychophysiological interaction analyses in CT demonstrated elevated connectivity of the amygdala and the insula for the comparison of pain under threat vs safety. In IT, the same comparison revealed elevated functional connectivity of the MCC and the insula. The results suggest a similar pain augmenting effect of CT and IT, which, however, seems to rely on different networks mediating the impact of threat on pain.