Is predictability of the conditioning stimulus (CS) a critical factor in conditioned pain modulation (CPM)?

Abstract

Introduction Conditioned pain modulation (CPM) allows to investigate endogenous pain modulation and its clinical outcomes. Although co-activation of emotions has been shown to affect CPM, the impact of ‘threat,’ which may accompany CPM stimulation itself, has been mostly neglected. A critical factor for the threat level of the conditioning stimulus (CS) may be its predictability. Methods 38 healthy participants (18 female) took part in a CPM study with pressure stimulation on the leg (blood-pressure cuff) serving as CS and heat stimulation on the forearm (contact thermode; CHEPS) serving as test stimulus (TS). While CS varied in intensity and –as operationalisation of threat– in temporary predictability, TS was kept constant. CPM effects were studied by EEG parameters (N2P2) and pain ratings. Results We found a significant CPM effect when considering N2P2, with low CS predictability augmenting CPM inhibition; in contrast, a surprisingly facilitatory CPM effect occurred in pain ratings (in the high CS predictability condition). The threat manipulation was only partially successful because CS intensity increased the threat ratings but not -as intended- CS predictability. Correlations between subjective and psychophysiological CPM responses were low. Discussion The differing CPM effects in subjective and psychophysiological responses, with both inhibitory and facilitatory effects, is puzzling but has already been observed earlier. The consideration of the CPM stimulation as major threat that is emotionally active is theoretically clearly justifiable but the operationalisation by means of different levels of CS predictability as in the present study might not have been ideal. Thus, further attempts of experimental verification are warranted.