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

ObjectiveWaiting 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.MethodsWe 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.ResultsSubjects (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.ConclusionsDistinct neural networks contribute to the P2 and are differentially affected by pain anticipation duration and unpredictability in stimulus timing.SignificanceERP research into dread should be careful to appreciate the neural generators of pain-evoked responses and their potential modulation by unpredictability.