To calibrate or not to calibrate? A methodological dilemma in experimental pain research

Abstract

To calibrate or not to calibrate? This question is raised by almost everyone designing an experimental pain study with supra-threshold stimulation. The dilemma is whether to individualize stimulus intensity to the pain threshold / supra-threshold pain level of each participant or whether to provide the noxious stimulus at a fixed intensity so that everyone receives the identical input. Each approach has unique pros and cons which need to be considered to i) accurately design an experiment, ii) enhance statistical inference in the given data and, iii) reduce bias and the influence of confounding factors in the individual study e.g., body composition, differences in energy absorption and previous experience. Individualization requires calibration, a procedure already irritating the pain system but allowing to match the pain level across individuals. It leads to a higher variability of the stimulus intensity, thereby influencing the encoding of “noxiousness” reaching the central nervous system. Results might be less influenced by statistical phenomena such as ceiling/floor effects and the approach does not seem to rise ethical concerns. On the other hand, applying a fixed (standardized) intensity reduces the problem of intensity encoding leading to a large between-subjects variability in pain responses. Fixed stimulation intensities do not require pre-exposure. It can be proposed that one method is not preferable over another, however the choice depends on the study aim and the desired level of external validity. This paper discusses considerations for choosing the best approach for experimental pain studies and provides recommendations for different study designs.

How to make calibration less painful—A proposition for an automatic, reliable and time‐efficient procedure

“…Typically, those studies employ diverse stimulus intensities (e.g., non-painful, mid, and high painful stimulation) which can be determined through a wide range of calibration procedures. Calibration is implemented to map the objective stimulation intensity to the individual's subjective perception of pain, such as pain threshold (T), and align it with commonly used pain response scales, such as visual analog scales (VAS) or the numeric rating scale (NRS; Adamczyk et al, 2022;Parhizgar & Ekhtiari, 2010). Despite the efforts to find better assessment methods (Gruss et al, 2019;Lautenbacher et al, 2022;Lundeberg et al, 2001;Wang et al, 2022), subjective self-report scales remain prevalent in both laboratory and clinical settings (Karcioglu et al, 2018;Williamson & Hoggart, 2005), notwithstanding their inherent limitations and weaknesses (Wagemakers et al, 2019).…”

“…It applies the stimuli near the threshold being measured and does not require as many stimulus applications, as is typically needed in the case of the continuous stimuli method (Watson & Fitzhugh, 1900); nevertheless, it is not without limitations (Johnson, 2016). For individuals with high or low pain sensitivity, it may lead to ceiling or floor effects, hence rendering accurate measurement of the pain threshold impossible (Adamczyk et al, 2022). Furthermore, repetitive stimulation may cause habituation or sensitization, which can potentially affect the accuracy of the results (Paul et al, 2021).…”

How to make calibration less painful – a proposition of an automatic, reliable and time-efficient procedure

“…The calibration protocols 4 , as well as modalities and characteristics of pain stimulation, highly differ from one study to another 3 , making comparisons between them challenging. A well-designed calibration procedure should be characterized by three factors: standardization (unified calibration protocols for specific stimulus types), automatization (environmental factors control and high replicability), and detailed description of its implementation (e.g.…”