Offset analgesia: A reproducibility study.

Background and aims/objectives Offset analgesia (OA) is a newly discovered pain-inhibiting mechanism, defined as a disproportionately large decrease in pain perception in response to a decrease in noxious stimulus intensity. Offset analgesia is usually evoked using heat as noxious stimulus (44-47 °C) and a slight decrease (1 °C) in stimulus intensity causes the volunteers to be pain-free for 5-10 s, despite the presence of a constant noxious stimulus. The aim of the present study was to evaluate whether the OA phenomenon is reproducible within the same day and between different days in order to evaluate whether the phenomenon can be used as a prognostic/diagnostic tool or as a potential therapeutic target in pain treatment. Methods Eighteen healthy volunteers were presented to painful thermal stimuli on the volar forearm, in three contiguous phases (first phase: 46 °C applied for 5 s; second phase: 47 °C applied for 5 s; third phase: 46 °C applied for 20 s). Continuous sensory ratings obtained with a handheld sliding VAS-scale and continuous 64-channel electroencephalographic (EEG) recordings were obtained throughout the three phases. Volunteers participated on two different days separated by a minimum of 7 days. Results Reproducibility was examined for numerous parameters (e.g. peak pain intensity, magnitude of pain-relief, AUC) related to the continuous pain ratings. Two-way ANOVA, ICC, and CV displayed a high degree of reproducibility both within the same day as well as between different days (P-values >0.05 and ICC values >0.6). EEG recordings were decomposed by spectral analysis, to obtain the normalized power in the delta, theta, alpha, beta and gamma frequency bands. Conclusion The present model displayed high reproducibility, making it suitable for further studies using OA. This may provide a unique approach to study basic pain and pharmacological intervention in healthy volunteers as well as in patients with dysfunctional pain inhibition. Continuous EEG recordings enable objective evaluation of dynamic changes in brainwave activity during OA, and can possibly be used as an objective biomarker to assess the underlying mechanisms of OA.