Neural and psychological mechanisms of pain perception

National Center For Complementary & Integrative Health

Investigators

Linked publications, trials & patents

Abstract

This was the eleventh year of the Section on Affective Neuroscience and Pain, and the lab continued to progress, recruit new staff members and trainees, and plan new studies. One staff scientist and four fellows (one postdoc, three postbacs) joined the lab between October 2024 and September 2025. This progress report describes progress on 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 analyzed, submitted, and published several papers related to this protocol during the review period. 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 participant’s pain threshold, tolerance, and reliability of the association between temperature and pain. Over 400 individuals have completed this procedure to date on this protocol or on our pre-screening protocol (16-AT-0077). In FY24, we conducted an initial study using two different thermodes to test whether thermode type and stimulus duration impact pain sensitivity as measured using the ASC task. In FY25, we conducted a second study (n = 36) to test for replication of our initial findings and control for the effect of thermode. In each study, participants underwent the ASC task twice during a visit, and we compared pain sensitivity as a function of stimulus duration. Analyses indicate that stimulus duration affects pain tolerance, but not pain threshold, which provides support for standard QST tasks that focus on pain threshold in clinical populations, and suggests that suprathreshold measures may be more sensitive to experimental influences. We are currently preparing this manuscript for publication (Wei et al., In prep) and expect to submit in late FY25. We published one of our key FMRI sub-studies in FY25 (Necka et al., Journal of Neuroscience). In this study, we compared two forms of expectancy-based pain modulation: placebo analgesia and pain-predictive cues. We found that the two forms of modulation are supported by both separate and interacting brain mechanisms. Our findings indicate that clinicians should be aware that pain is shaped by both information about painful procedures and information about analgesic treatments, and that researchers should not use cues as a model of placebo analgesia. We also submitted a manuscript on our third FMRI sub-study, which 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. We observe effects of cues on intensity processing in all domains, and find domain-general impacts of expectancy on brain responses regardless of modality (Zhao*, Lee*, et al., Invited revision). We anticipate that the manuscript will be accepted for publication in late FY25 or early FY26. During FY25, we began piloting a paradigm that will build on our comparisons between pain and other aversive modalities. Rather than using Pavlovian conditioning to study expectations, we will measure decision-making between different aversive outcomes and evaluate whether expected value computations depend on domain-general or domain-specific networks. Task development and piloting will be complete by the end of FY25 and we expect formal data collection and fMRI scanning to commence in early FY26. In addition to the projects mentioned above, we published collaborative papers and reviews that are relevant to this line of research. We evaluated the link between skin conductance and salience ratings to address how researchers can control for salience during pain studies (Hajdist et al., PAIN, 2025). We are also preparing a “manyverse” analysis of associations between skin conductance and pain to determine the definitive processing pipeline that might allow researchers to use autonomic responses as a biomarker for pain (Delity et al., in prep); we expect this manuscript to be submitted in late FY25 or early FY26. We also published an invited review of the relationship between pain and value-based decision-making (Lopez-Guzman and Atlas, In press). Finally, we published a longitudinal study of the relationship between loneliness, psychiatric vulnerability, and mental health during the first year of the COVID-19 pandemic (Atlas et al., 2025, Nature Mental Health) and submitted another paper on the relationship between chronic pain and mental health during the COVID-19 pandemic.