Neural dynamics of parametrically modulated human mechanical pain determined using whole-brain quantitative perfusion imaging

Abstract

Arterial spin labelling (ASL) FMRI is a powerful tool to non-invasively image tonic and ongoing pain states in both healthy participants and patients. We used ASL to image the neural correlates of extended, parametrically modulated mechanical pain in healthy human participants. The aims of this study were to: i) assess if force-calibrated pin-prick probes could safely and robustly evoke tonic mechanical pain; ii) determine the neural correlates of the parametric changes in both the force of the stimulus and the intensity of the perception that this elicits using ASL; and iii) provide an initial assessment of the capacity for amplitude of low-frequency fluctuation (ALFF) to differentiate painful versus non-painful tonic stimuli based on changes in the dynamics of the evoked signal. Our data confirm that it is possible to employ a stimulus force-locked design to induce robust, well maintained ongoing mechanical pain and to observe significant changes in rCBF relative to underlying component processes such as monitoring graded changes in the force applied to the skin (e.g., dACC, aMCC, pMCC, PCC, SI, SII, putamen, thalamus and the insula (anterior and posterior subsections); ipsilateral amygdala and hypothalamus; and the contralateral DLPFC) and tracking changes in the perceived intensity of the experience (e.g., bilateral dACC, aMCC, pMCC, PCC, thalamus, SII and the cerebellum; and contralateral SI, insula (including the dpIns). Further exploration of the data using an ALFF analysis reveals that a collection of regions (e.g. the contralateral VLPFC, inferior frontal gyrus, insula (anterior, mid and posterior subsections), SII, putamen, OFC, amygdala, and the hippocampus) exhibit unique perfusion dynamics during extended painful stimulation compared to non-painful touch. Results from this study provide further validation for the application of ASL to image experimental pain in healthy human subjects while interrogation of the data offers unique insight into the dynamic signal changes underlying the perception of a tonic mechanical pain experience.