• Jaymin Upadhyay, Jordan Lemme, Julie Anderson, David Bleakman, Thomas Large, Jeffrey L Evelhoch, Richard Hargreaves, David Borsook, and Lino Becerra.
• Imaging Consortium for Drug Development, Boston, MA 02115, USA; Pain/Analgesia Imaging Neuroscience (P.A.I.N.) Group, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
• J. Neurosci. Methods. 2015 Sep 30; 253: 38-46.

AbstractTo date, the blood oxygenated-level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique has enabled an objective and deeper understanding of pain processing mechanisms embedded within the human central nervous system (CNS). In order to further comprehend the benefits and limitations of BOLD fMRI in the context of pain as well as the corresponding subjective pain ratings, we evaluated the univariate response, test-retest reliability and confidence intervals (CIs) at the 95% level of both data types collected during evoked stimulation of 40°C (non-noxious), 44°C (mildly noxious) and a subject-specific temperature eliciting a 7/10 pain rating. The test-retest reliability between two scanning sessions was determined by calculating group-level interclass correlation coefficients (ICCs) and at the single-subject level. Across the three stimuli, we initially observed a graded response of increasing magnitude for both VAS (visual analog score) pain ratings and fMRI data. Test-retest reliability was observed to be highest for VAS pain ratings obtained during the 7/10 pain stimulation (ICC=0.938), while ICC values of pain fMRI data for a distribution of CNS structures ranged from 0.5 to 0.859 (p<0.05). Importantly, the upper and lower confidence interval CI bounds reported herein could be utilized in subsequent trials involving healthy volunteers to hypothesize the magnitude of effect required to overcome inherent variability of either VAS pain ratings or BOLD responses evoked during innocuous or noxious thermal stimulation.Copyright © 2015 Elsevier B.V. All rights reserved.

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