Assessment of Differences in Temporal Pain Dynamics in Pain-Evoked fMRI Experiments Open Access
Rivera, Adrian (Spring 2022)
Published
Abstract
Pain-evoked functional magnetic resonance imaging (fMRI) experiments have helped uncover numerous features of the brain’s neural underpinnings of the pain experience. These analyses commonly contrast blood oxygenation level dependent (BOLD) responses to noxious stimuli applied in ON blocks (i.e., during application of a noxious stimulus) with the BOLD response during OFF blocks (i.e. during periods of no, or innocuous stimulation). In most studies, it is generally assumed that pain is experienced primarily during the ON blocks, with minimal pain experienced during OFF blocks. However, C fibers transmit nociceptive signals to the brain slowly (as slow as 0.5 m/s), leading to delays in the onset of pain, and painful after-sensations (AS) are sometimes experienced after noxious stimulation has ended. Previous research has shown that AS is greater in individuals with chronic pain (e.g. fibromyalgia), meaning that pain experienced during off blocks could add noise to the analysis pipeline by comparing groups who are not experiencing pain similarly over time. In many fMRI studies of pain, one to several discrete numeric rating scale (NRS; e.g. 0-100) pain ratings are obtained after the presentation of a noxious stimulus, capturing the overall rather than the moment-to-moment experience of the pain. Given that the temporal experience of pain may differ depending on the different modalities (e.g., thermal vs. mechanical) that are utilized in a study, the need to characterize the temporal nature of the pain experience of stimuli that are used in pain-evoked fMRI experiments is also essential. Therefore, in the present study we evaluated pain using a continuous visual analog scale (VAS) that recorded the experience of both a noxious mechanical and a noxious thermal stimulus on a moment-to-moment basis (every 0.1 sec). We assessed how stimulus type (thermal or mechanical), change in intensity (slowly increasing, constant, or slowly decreasing), and stimulus location (left vs. right calf) may influence the temporal progression of the pain experience during a typical fMRI block design experiment of 20 secs ON interleaved with 20 secs OFF. On average, participants took 8.63 secs (± 3.10) from the onset of the ON block to perceive the thermal stimuli as painful (i.e. > 5/100) and 5.12 secs (± 2.53) to perceive pain from the mechanical pressure stimuli. Stimulus intensity was not a predictor of when the stimulus would be perceived as painful, but rather stimulus type (whether noxious heat or noxious pressure) was the only predictor, with noxious heat taking longest to be perceived at all intensities. On aftersensations, participants reported noxious heat eliciting longer lasting painful sensations after the stimuli had been removed (time for pain to disappear was measured as VAS<5/100)—with the increasing and constant conditions taking longest to do so: 6.67 ± 2.09 secs and 6.62 ± 2.09 secs, respectively. Significantly, as many as 75% of subjects reported for the sensation of pain to reach its peak after stimulus had been turned off during the blocks where the increasing thermal stimulus was applied.
Conclusions: These results provide additional evidence that the temporal dynamics of the pain experience are not entirely in line with the onset and offset of the eliciting stimulus. Taking these nuances in the temporal dynamics of pain into account during analysis of pain-evoked BOLD could improve in the signal to noise ratio of the neural correlates of the pain experience. Modified blocks of time considering when subjects begin and stop perceiving a painful sensation, which varies dependent upon the intensity of a stimuli and the type of stimuli being applied, may ultimately lead to more precise assessment of this objective marker of pain. Our future analyses of the fMRI data from these same participants will use modified “perceived pain ON” and “perceived pain OFF” blocks accounting for these temporal differences.
Table of Contents
Introduction................................................................................................... 1
Methods......................................................................................................... 5
Results.......................................................................................................... 11
Discussion.................................................................................................... 16
Conclusion and Clinical Significance ............................................................ 22
Supplementary Figures.............................................................................. 23
References.................................................................................................. 29
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