Interpretation of subjective ratings within pain research: What about context effects? an induced secondary hyperalgesia example

Abstract

In many experimental and clinical studies, subjective ratings of experimentally induced pain experiences are used to evaluate the nociceptive function. However, our understanding of how these subjective ratings are produced and influenced is limited. Not taking into account variability in how the subjective responses are produced, e.g. due to experience with (experimental) pain, might lead to biased, underpowered or even misinterpreted studies or clinical decisions. Here, we illustrate such variability in the case of studying secondary hyperalgesia using High Frequency Stimulation (HFS) as a conditioning stimulus. Recently, different findings have been reported related to the effect of HFS on single electrical stimuli. While most studies report an increased pain rating at the test electrode after HFS relative to the control site, in some studies this difference between test and control ratings is the result of a decrease in pain ratings at the control site. In these reports, the observations are explained by nociceptive mechanisms like habituation or descending inhibition. In our view these mechanisms do not (fully) explain the observable event, nor the differences between the studies. Here, we provide a phenomenological analysis of the observable event and based on this analysis hypothesize that ratings can be affected by prior experience with experimental stimuli (i.e. familiarization with HFS). Acceptance of the hypothesis suggests the (co–)existence of alternative mechanisms at experiments with HFS, as earlier suggested underlying mechanisms are unable to explain these observations. We argue that both the observable event and the differences between the studies can be explained by mechanisms underlying so-called context effects, i.e. well-known phenomena in other sensory modalities whereby the participant’s response is altered based on earlier provided stimuli. Importantly, from a theoretical perspective context effects could (have) play(ed) a role in (many) more experimental procedures within pain research than only when HFS is used, but seemingly to date have not received attention. Consequently, with some experimental procedures within pain research, observed variation might be wrongly attributed to changes in nociceptive function due to an explanatory focus on nociceptive mechanisms. On the short-term, acceptance of the hypothesis highlights an urgent need to perform research in which the effect and magnitude of context effects are evaluated in commonly performed procedures within pain research. On the long-term, dependent on the findings of these studies, this might lead to revisiting not only experimental (familiarization) procedures, but also revising the way earlier results from these experimental procedures have been interpreted.