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Pain in the brain - Factors influencing pain perception and its modulation
Donnerstag, 03.06.2021:
10:15 - 11:45

Chair der Sitzung: Marian van der Meulen, University of Luxembourg
Ort: Clinical challenges and the ageing brain

Zusammenfassung der Sitzung

The way noxious stimuli are perceived is highly dependent on factors, such as the current attentional state or expectations about the painful event. Distraction from pain and placebo analgesia are prominent examples for this cognitive modulation of pain. Although these are generally very powerful mechanisms of pain modulation, prior studies have found considerable interindividual variations in the magnitude of the modulatory effect, while little is known about the influencing factors.

Here, we present a series of studies on cognitive and situational factors influencing pain perception and its modulation on the behavioural and (neuro)physiological level. A special focus is on the role of age-related changes, since little is known about a potentially altered “top-down” control of pain in old age, albeit this population is disproportionately affected by pain and its consequences.

Ana María González Roldán presents a study on age-related changes in pain processing and associated resting-state functional connectivity of regions implicated in pain processing. Turning to cognitive distraction from pain, Katharina Rischer discusses age-related neural changes and the role of executive functions therein. Complementary, Elisabeth Holl reports on the analgesic response and associated changes in heart rate and electrodermal activity in young adults, playing a distracting virtual reality game. The impact of age on the processing of acute pain and on its neural correlates is addressed by Angelika Dierolf. Shervin Vencatachellum discusses the role of mindfulness in shaping expectations about pain, by considering recent neuroimaging insights within the interoceptive predictive coding framework.

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Resting-state brain activity and pain alterations in aging

Ana M González-Roldán

University of Balearic Islands, Spain

Aging affects pain experience and brain functioning. However, how aging lead to changes in pain perception and brain functional connectivity have not yet been completely understood. In a series of studies, we analyzed imaging data (EEG and fMRI) to investigate resting-state and pain perception changes in old and young adults. Thirty-seven older and 38 younger healthy participants underwent 10 minutes’ eyes-closed fMRI scanning. Moreover, part of these participants underwent a resting-state EEG recording followed by a painful stimulation paradigm with different levels of attention to pain. We examined the relationship between resting-state functional connectivity parameters with pressure pain thresholds as well as with pain intensity and unpleasantness ratings elicited by painful stimulation. Older participants showed higher pain thresholds and pain ratings than younger. Older adults displayed increased connectivity between pain-related sensory brain regions and reduced connectivity among descending modulatory areas in comparison to younger participants. Correlational analyses showed that functional connectivity between the primary and secondary somatosensory area was positively associated with pressure pain thresholds in older participants. Moreover, beta 3 activity from anterior cingulate cortex (ACC) was positively correlated with pain intensity and unpleasantness ratings in older adults; and ACC-precentral/postcentral gyrus connectivity was positively correlated with unpleasantness ratings in older and younger adults. Altogether, these studies offer new insights into the evolution of cortical networks in normal aging and its relevance to pain perception. Furthermore, these results could explain the greater vulnerability to chronic pain disorders in older individuals. Supported by the Spanish Ministry of Science and Innovation (PID2019-110096GB-I00AEI/FEDER-UE).

Cognitive distraction from pain: An fMRI study on the role of age and executive functions

Katharina M. Rischer1, Angelika Dierolf2, Ana M. González-Roldán3, Pedro Montoya3, Fernand Anton1, Marian van der Meulen1

1University of Luxembourg; 2University of Trier; 3University of the Balearic Islands

Completing a cognitive task has been shown to be a powerful strategy to reduce concurrent pain. This reduction in pain is assumed to result from a competition between the painful stimulus and the distractive task for attentional and executive resources mediated by the prefrontal cortex (PFC), a region that is particularly affected by age-related grey matter atrophy. In the present study, we investigated the role of age-related changes in gray matter volume and executive functions in modulating the efficacy of distraction from pain.

In a first session, young and older adults completed a battery of neuropsychological tests. In a second session, we acquired functional brain images while participants completed a working memory task with two different levels of cognitive load (low vs. high load) and concurrently received individually adjusted heat stimuli (innocuous vs. painful) to their lower arm.

While we found no age-related differences in the distraction effect size on the behavioural level, young adults showed a larger neural distraction effect in several regions involved in pain processing, including the insula, caudate and midcingulate cortex. Interestingly, older adults with better executive functions, particularly, better inhibitory control abilities, showed a larger neural distraction effect in the insula, thalamus and primary somatosensory cortex, and more activation in frontal clusters during the high load task.

Altogether, these findings suggest that age alters the neural mechanisms underlying cognitive distraction from pain, and that the magnitude of these changes may be dependent on the preservation of executive functions.

Analgesic effects of interacting with a VR game and associated psychophysiological responses

Elisabeth Holl, Katharina Rischer

Universität Luxembourg, Luxembourg

Introduction: Virtual reality (VR) has been shown to be an effective tool for pain distraction by redirecting attention away from painful stimuli. Although VR therapy has been successfully implemented in clinical settings, little is known about the underlying factors that modulate analgesic responses, such as cognitive load, executive functions and VR or gaming experience.

Methods: A final sample of N = 90 healthy participants played the VR game Subnautica in a high and a low cognitive load condition. In the low load condition, participants explored the VR along a predefined route. In the high load condition, participants had to additionally memorize eight digits presented along the route. Pain heat thresholds as well as psychophysiological measures (ECG, EDA) were recorded during a non-interactive resting state period prior to playing as well as during the two VR sessions. Furthermore, participants completed questionnaires (e.g., pain attitude) and executive functioning tasks (e.g., go/nogo task).

Results: Pain thresholds did not differ for high versus low demand. However, participants achieved higher threshold for the interactive playing sessions compared to the resting state period. Psychophysiological markers (e.g., HRV) indicate lower sympathetic activity during the resting state compared to the playing session (resting state < low load < high load). Moreover, pain catastrophizing and fear of pain were significant predictors of pain thresholds.

Discussion: Results shed light on the role of inter-individual differences and psychophysiological markers of VR-based pain sensitivity and indicate factors that facilitate/impair distraction effects. This may have important implication for the use of VR-therapy.

Pain processing in older age – evidence from event-related potentials

Angelika Dierolf1, Katharina Rischer2, Ana M. González-Roldán3, Montoya Pedro3, Fernand Anton2, Marian van der Meulen2

1Universität Trier, Deutschland; 2University of Luxembourg; 3University of the Balearic Islands

Aging is known to affect neurobiological and physiological aspects of pain perception and has been associated with reduced pain sensitivity and a deterioration of descending pain inhibitory mechanisms. To investigate age differences in neural electrophysiological correlates of pain processing, we induced acute pain in healthy older (60 yrs+) and younger adults (18 to 35 yrs), using short transdermal electrical pulses administered to the inner forearm, with individually adjusted stimulation intensities. Participants received alternating blocks of painful and non-painful control stimulation and rated the intensity and unpleasantness of each stimulus on two visual analog scales. Pain-related evoked potentials were recorded with a 64-channel EEG.

Preliminary results indicate that younger and older participants rated painful stimuli more intensive and unpleasant compared to the control stimulation, with older adults showing a slight habituation over time. In younger adults, ERP amplitudes (N2, P2 P3) of painful stimulation were enhanced compared to non- painful stimulation. In contrast, older participants showed generally reduced ERPs, no difference between pain and non-painful stimulation and by tendency longer latencies for painful stimulation.

This suggests that nociceptive neural processing is altered in aging, while the reported pain perception is unaffected. Given that aging is also associated with a decline of cognitive functions and PFC volume and activity changes, this could have implications for the efficacy of cognitive pain modulation. Altogether, our results highlight the need for a deeper understanding of the mechanisms underlying pain processing in older adults, and how these age-related changes affect (cognitive) pain treatments in this population.

Reduced sensitivity to pain expectations in mindfulness? Evidence from a pain-cueing paradigm

Shervin Vencatachellum

University of Luxembourg, Luxembourg

Recent insights from neuroimaging studies suggest that mindfulness-based interventions may alleviate pain via a unique neural mechanism, involving increased sensory processing and reduced memory-driven evaluative processing. These findings raise the intriguing possibility that mindfulness may mitigate the well-documented biasing influence of prior cognitive and emotional expectations on pain perception. We tested this hypothesis across two separate studies, using a classical pain cueing paradigm which has been shown to reliably elicit conditioned hypoalgesic and hyperalgesic effects.

In the first study, healthy non-meditators were assigned to listen to either brief mindfulness or suppression instructions, in between the conditioning and testing phases of an implicit pain-cueing task. In the second study, we compared high vs. low trait mindfulness scorers during an explicit pain conditioning task. Throughout both studies, participants were asked to rate the level of anticipatory anxiety, pain intensity and pain unpleasantness that they experienced during each trial.

Findings from the first study revealed that instructed use of a mindfulness strategy resulted in reduced conditioned hypoalgesia relative to the suppression instructions. For the second study, we found evidence of reduced conditioned hyperalgesia in the high trait mindfulness group. Altogether, these findings are consistent with the notion that mindfulness-induced pain relief relies on distinct, and possibly counteracting, neuropsychological mechanisms to those involved in expectancy-driven pain modulation. I will discuss our results in light of existing neuroimaging evidence and recently formulated predictive processing models of mindfulness which posit that mindful attention leads to a prioritization of incoming sensory information over prior beliefs.

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