Neural and psychological mechanisms of pain perception

National Center For Complementary & Integrative Health

Investigators

Linked publications & trials

Abstract

This was the seventh year of the Section on Affective Neuroscience and Pain, and despite setbacks due to the pandemic, the lab continued to progress, recruit new trainees, and see former fellows move on to exciting new positions. Two postbac fellows completed their training and began graduate school (medical school; clinical psychology PhD program), and three new fellows (one postdoc, two postbacs) joined the lab between October 2020 and August 2021, and two more postbacs will join by the end of this fiscal year. This progress report describes progress on our our main human subjects protocol Neural and psychological mechanisms of pain perception. The protocol includes five sub-studies designed to a) isolate different aspects of pain modulation, b) compare acute pain modalities (e.g., thermal pain versus shock-induced pain), and c) compare and contrast pain with other hedonic and perceptual domains (e.g., taste). In all studies, we measure decisions about pain experience (self-report) as well as neural and physiological responses to noxious stimuli that cause pain. During analysis, we combine computational modeling with advanced neuroimaging analyses to isolate the neural and psychological mechanisms that mediate the effects of expectations, attention, and emotion on subjective pain. We were required to the need to halt healthy volunteer research due to the COVID19 pandemic, which had a serious impact on our ability to make progress with data collection on this healthy volunteer protocol. However, we shifted gears to focus on data analysis, as well as other experiments that involve online data collection. Our protocol requires all participants to go through an initial calibration session, following screening. Participants complete questionnaires, and then undergo an adaptive staircase calibration (ASC) procedure that evaluates pain ratings in response to noxious heat stimuli and determines each participants pain threshold, tolerance, and reliability of the association between temperature and pain. 338 individuals completed this procedure to date. We published two manuscripts based on this ASC procedure in the past fiscal year (Dildine, Necka, and Atlas, 2020 Scientific Reports; Mischkowski et al., 2021, Psychosomatic Medicine) and submitted one additional manuscript (Amir et al., Under review). A subset of participants provided confidence ratings during the ASC task, and we analyzed the association between confidence in pain ratings and implicit behavioral measures during the pain rating process, namely eye tracking and reaction time (Dildine, Necka, and Atlas 2020, Scientific Reports). For the first time, we demonstrated that individuals can provide meta-cognitive judgments about their subjective pain, and that confidence is predicted by reaction time during pain rating. In future work, we will draw on these findings to measure the associations between expectations, uncertainty, and pain. We hypothesize that placebos might decrease pain but increase uncertainty. We also measured the association between dispositional mindfulness and pain during the ASC task (Mischkowski et al., 2021, Psychosomatic Medicine). We found that individuals who report higher levels of mindfulness report less pain in post-task questionnaires, but show no difference in pain ratings collected during or immediately after noxious stimulation. This suggests that the analgesic effect of mindfulness might be more linked to reappraisal of pain than the actual nociceptive process itself. Of the 338 participants who completed the ASC procedure, 171 participants completed more than one visit and underwent the calibration procedure on each visit. This allowed us to evaluate the reliability of pain sensitivity measures derived from the ASC task to determine whether individuals report stable pain sensitivity across sessions (Amir et al., Under Review). We found that pain thresholds and tolerance were moderately reliable, but that the correlation between temperature and pain has low reliability across visits. Critically, we also examined sex differences in reliability, since hormonal fluctuations are often cited as a reason to exclude female participants from pain research. Strikingly, we found that female participants were more reliable than male participants for all three pain measures. We recently submitted these findings for publication and are currently undergoing peer review. We completed data collection for three fMRI sub-studies in previous years and are currently preparing manuscripts for submission. One experiment evaluates the effects of instructions and learning on pain and brain-responses to noxious stimulation during reversal learning. We find that individuals show similar cue-based modulation of pain and pain-related responses regardless of whether they are instructed about contingencies, but that learning related responses differ between groups (Atlas et al., Submitted). We also see dissociations within brain regions involved in pain modulation, such that some regions such as the insula reverse as contingencies change, whereas others such as the periaqueductal gray and thalamus are modulated by initial learning regardless of reversals. We are also analyzing fMRI data from a study that compared thermal pain with unpleasant and pleasant tastes to evaluate whether effects of learned expectations on brain responses to pain are specific to pain or reflect domain-general value processing (Lee et al., In prep). We observe stronger modulation of subjective intensity than valence, and the magnitude of expectancy effects on perceived intensity did not differ as a function of modality. We are now measuring whether the brain mechanisms that mediate these links differ as a function of modality. We are also analyzing data from an fMRI study that compared placebo analgesia with cue-based pain modulation (Akintola*, Necka*, et al., In prep). Although we hypothesized that the two types of expectancy modulation would rely on separate mechanisms, we found that they interacted behaviorally, such that cues mattered less under placebo. We are currently evaluating whether brain responses involved in pain modulation show similar interactions or whether separate systems process cue-based and placebo-based expectations. Both of these projects were led by fellows who completed their fellowships in the summer of 2019 and we are continuing to collaborate to complete analyses and draft the manuscripts, with the help of new trainees and our data analyst. Although we received approval to resume healthy volunteer research in late Spring 2021, all but one of the lab fellows joined during the pandemic and therefore no one is familiar with data collection procedures prior to the pandemic. Therefore training has gone slower than anticipated, and we have yet to resume data collection on this protocol. However, the two new postdocs have recently completed training and are designing the final sub-studies on this protocol. We are planning to resume data collection this summer to measure the relationship between attention and perception, and resume piloting our follow up experiment comparing pain and taste perception with high resolution 7-tesla MRI. In addition to the projects mentioned above, we published several collaborative papers, reviews, and commentaries that are relevant to this line of research including two papers on the effects of instructions and learning on pain and aversive learning in psychiatric populations (Abend et al., 2021, Journal of Psychiatry and Neuroscience; Lebedev et al., 2021, Scientific Reports), one review on placebo analgesia (Atlas, In press, Trends in Cognitive Sciences), and two collaborative papers on pain and placebo analgesia (Zunhammer et al., 2021; Evers et al, 2021, Psychotherapy and Psychosomatics).