Differential Effects of Thermal Stimuli in Eliciting Temporal Contrast Enhancement: A Psychophysical Study.

Offset analgesia (OA) is observed when pain relief is disproportional to the reduction of noxious input and is based on temporal contrast enhancement (TCE). This phenomenon is believed to reflect the function of the inhibitory pain modulatory system. However, the mechanisms contributing to this phenomenon remain poorly understood, with previous research focusing primarily on painful stimuli and not generalizing to nonpainful stimuli. Therefore, the aim of this study was to investigate whether TCE can be induced by noxious as well as innocuous heat and cold stimuli. Asymptomatic subjects (n = 50) were recruited to participate in 2 consecutive experiments. In the first pilot study (n = 17), the parameters of noxious and innocuous heat and cold stimuli were investigated in order to implement them in the main study. In the second (main) experiment, subjects (n = 33) participated in TCE paradigms consisting of 4 different modalities, including noxious heat (NH), innocuous heat (IH), noxious cold (NC), and innocuous cold (IC). The intensity of the sensations of each thermal modality was assessed using an electronic visual analog scale. TCE was confirmed for NH (P < .001), NC (P = .034), and IC (P = .002). Conversely, TCE could not be shown for IH (P = 1.00). No significant correlation between TCE modalities was found (r < .3, P > .05). The results suggest that TCE can be induced by both painful and nonpainful thermal stimulation but not by innocuous warm temperature. The exact underlying mechanisms need to be clarified. However, among other potential mechanisms, this may be explained by a thermo-specific activation of C-fiber afferents by IH and of A-fiber afferents by IC, suggesting the involvement of A-fibers rather than C-fibers in TCE. More research is needed to confirm a peripheral influence. PERSPECTIVE: This psychophysical study presents the observation of temporal contrast enhancement during NH, NC, and innocuous cold stimuli but not during stimulation with innocuous warm temperatures in healthy volunteers. A better understanding of endogenous pain modulation mechanisms might be helpful in explaining the underlying aspects of pain disorders.

Investigation of Correlations Between Pain Modulation Paradigms.

OBJECTIVE: Endogenous pain modulation can be quantified through the use of various paradigms. Commonly used paradigms include conditioned pain modulation (CPM), offset analgesia (OA), spatial summation of pain (SSP), and temporal summation of pain (TSP), which reflect spatial and temporal aspects of pro- and antinociceptive processing. Although these paradigms are regularly used and are of high clinical relevance, the underlying physiological mechanisms are not fully understood. DESIGN: The aim of this study is therefore to assess the association between these paradigms by using comparable protocols and methodological approaches. SETTING: University campus. SUBJECTS: Healthy and pain-free volunteers (n = 48) underwent psychophysical assessment of CPM, OA, SSP, and TSP (random order) at the same body area (volar nondominant forearm) with individualized noxious stimuli. METHODS: CPM included heat stimuli before, during, and after a noxious cold-water bath, whereas for OA, three heat stimuli were applied: baseline trial, offset trial, and constant trial. For the SSP paradigm, two differently sized heat stimulation areas were evaluated, whereas for TSP, the first and last stimulus of 10 consecutive short heat stimuli were assessed. A computerized visual analog scale was used to continuously evaluate pain intensity. The magnitudes of all associations between all paradigm pairs were analyzed with Spearman's correlation, and individual influencing factors were assessed with a multivariate linear regression model. RESULTS: Weak to moderate correlations among all four paradigms were found (P > 0.05), and no distinct influencing factors were identified. CONCLUSIONS: A limited association between pain modulation paradigms suggests that CPM, OA, SSP, and TSP assess distinct aspects of endogenous analgesia with different underlying physiological mechanisms.