Offset analgesia is increased intra-orally.

BACKGROUND: Offset analgesia (OA) is commonly used to quantify endogenous pain inhibition. However, the potential role of afferent inputs and the subsequent peripheral factors from different body areas on the underlying mechanisms are still unclear. OBJECTIVES: The aim of this cross-sectional study was to compare the magnitude of OA in four different body areas representing (a) glabrous and non-glabrous skin, (b) trigeminal and extra-trigeminal areas, and (c) intra- and extra-oral tissue. METHODS: OA was assessed at the oral mucosa of the lower lip, the skin of the cheek, the forearm and the palm of the hand in 32 healthy and pain-free participants. OA testing included two trials: (1) a constant trial (30 s of constant heat stimulation at an individualised temperature of Pain50 [pain intensity of 50 out of 100]) and (2) an offset trial (10 s of individualised Pain50 , followed by 5 s at Pain50 + 1°C and 15 s at Pain50 ). Participants continuously rated their pain during each trial with a computerised visual analogue scale. RESULTS: A significant OA response was recorded at the oral mucosa (p < .001, d = 1.24), the cheek (p < .001, d = 0.84) and the forearm (p < .001, d = 1.04), but not at the palm (p = .19, d = 0.24). Significant differences were shown for OA recorded at the cheek versus the mucosa (p = .02), and between palm and mucosa (p = .007), but not between the remaining areas (p > .05). CONCLUSION: This study suggests that intra-oral endogenous pain inhibition assessed with OA is enhanced and supports the role of peripheral mechanisms contributing to the OA response.

Temporal properties of pain contrast enhancement using repetitive stimulation.

BACKGROUND: Offset analgesia (OA) is characterized by a disproportionately large reduction in pain following a small decrease in noxious stimulation and is based on temporal pain contrast enhancement (TPCE). The underlying mechanisms of this phenomenon are still poorly understood. This study is aiming to investigate whether TPCE can also be induced by repetitive stimulation, i.e., by stimuli clearly separated in time. METHODS: A repetitive TPCE paradigm was induced in healthy, pain-free subjects (n = 33) using heat stimuli. Three different interstimulus intervals (ISIs) were used: 5, 15, and 25 s. All paradigms were contrasted with a control paradigm without temperature change. Participants continuously rated perceived pain intensity. In addition, electrodermal activity (EDA) was recorded as a surrogate measure of autonomic arousal. RESULTS: Temporal pain contrast enhancement was confirmed for ISI 5 s (p < 0.001) and ISI 15 s (p = 0.005) but not for ISI 25 s (p = 0.07), however, the magnitude of TPCE did not differ between ISIs (p = 0.11). A TPCE-like effect was also detected with increased EDA values. CONCLUSIONS: TPCE can be induced by repetitive stimulation. This finding may be explained by a combination of the mechanisms underlying the OA and a facilitated pain habituation. SIGNIFICANCE: This experiment shows for the first time that temporal contrast enhancement of pain can be elicited by stimuli that are clearly separated in time with an interstimulus interval below 25 s.

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.