Dissociating nociceptive modulation by the duration of pain anticipation from unpredictability in the timing of pain

Objective Waiting longer to receive pain increases its perceived unpleasantness by inducing ‘dread’. However, it is not clear how unpredictability in the timing of the impending pain stimulus interacts with dread and whether the two factors show differential effects on the neural generators of the pain-evoked response. Methods We manipulated the duration of anticipation of laser-induced pain independently of unpredictability of stimulus delivery timing, to observe the relative effect on P2 amplitudes of the laser-evoked potential (LEP) response and its estimated sources. Results Subjects (n = 12) reported increased pain ratings after longer pain anticipation, irrespective of unpredictability in the timing of stimulus delivery. By contrast, unpredictability in stimulus timing increased the amplitude of the P2 irrespective of anticipation duration. The modulation of P2 amplitude by unpredictability was localized to midcingulate cortex (MCC) and ipsilateral secondary somatosensory (S2) areas. Greater anticipation duration increased activity in a hippocampal-insula-prefrontal network but not in MCC areas. Conclusions Distinct neural networks contribute to the P2 and are differentially affected by pain anticipation duration and unpredictability in stimulus timing. Significance ERP research into dread should be careful to appreciate the neural generators of pain-evoked responses and their potential modulation by unpredictability