Not just a matter of pain intensity: Effects of three different conditioning stimuli on conditioned pain modulation effects

INTRODUCTION: Heterotopic conditioned pain modulation (CPM) has provided potentially useful clinical information such as response to medication in neuropathic pain or the prediction of pain after surgical procedures. Despite these advances, several methodological aspects of CPM remain to be determined, such as the impact of the conditioning stimulus (CS) type upon CPM, if its evoked-pain intensity is controlled for [measured on a visual analogue scale (VAS: 0-100mm)].

OBJECTIVES: To explore potential differential effects of CPM using three distinct CS (having similar evoked-pain intensity) in the same individuals.

METHODS: We conducted a cross-over randomized study in healthy volunteers (HV) and looked-for differences in the CPM effect evoked by three differing CS [cuff-pressure pain stimulation (CuPS), cold pressor test (CoPT), and thermode-based cold painful stimulation (TCPS)] on the same test stimulus [(TS)-supra-threshold heat pain stimulation with a contact-heat thermode). CPM was calculated as a ratio: [conditioned TS VAS - unconditioned TS VAS]/[unconditioned TS VAS]. Importantly, the range of pain evoked by the unconditioned-TS and by the CS was controlled for. Also, the unpleasantness evoked by the CS [visual analogue scale (VAS: 0-100mm)] was measured before the initiation of the conditioned-TS.

RESULTS: Pain intensity VAS of the three unconditioned-TSs were similar between the three sessions. CPM was significantly different between the three types of CS (CoPT=-0.43±0.29; CuPS=-0.25±0.24; and TCPS=-0.23±0.35; P=.005): CoPT induced significantly more robust CPM compared to CuPS (P=.004) and TCPS (P=.005).

CONCLUSIONS: Significantly different intensities of CPM can be evoked on the same individual according to the nature of the CS, even when controlling for the intensity of the unconditioned-TS, and the pain evoked by the CS. This may have implications for the design of future recommendations and may impact the translation of CPM from the laboratory to clinical practice.