The Role of Chronic Stress in Normal Visceroception: Insights From an Experimental Visceral Pain Study in Healthy Volunteers

Abstract

Visceroception is a complex phenomenon comprising the sensation, interpretation, and integration of sensations along the gut-brain axis, including pain or defecatory urgency. Stress is considered a crucial risk factor for the development and maintenance of disorders of gut-brain signaling, which are characterized by altered visceroception. Although the broad role of stress and stress mediators in disturbed visceroception is widely acknowledged, the putative contribution of chronic stress to variations in normal visceroception remains incompletely understood. We aimed to elucidate the role of chronic stress in shaping different facets of visceroception. From a well-characterized, large sample of healthy men and women (N = 180, 50% female), volunteers presenting with low (n = 57) and elevated (n = 61) perceived chronic stress were identified based on the validated Trier Inventory for Chronic Stress (TICS). Visceral sensitivity together with perceived and recalled intensity and defecatory urgency induced by repeated rectal distensions was experimentally assessed, and compared between low and elevated stress groups. Subgroups were compared regarding state anxiety and salivary cortisol concentrations across experimental phases and with respect to psychological measures. Finally, in the full sample and in chronic stress subgroups, a recall bias in terms of a discrepancy between the perception of experimentally-induced symptoms and their recall was tested. Participants with elevated chronic stress presented with increased state anxiety and higher cortisol concentrations throughout the experimental phases compared to the group with low chronic stress. Group differences in visceral sensitivity were not evident. The elevated stress group perceived significantly higher urgency during the stimulation phase, and recalled substantially higher feelings of urgency induced by rectal distensions, while perceived and recalled intensity were comparable between groups. Volunteers with elevated stress exhibited a recall bias in terms of a higher recall relative to mean perception of urgency, whereas no such bias was observed for the intensity of experimental visceral stimulation. Our findings in healthy men and women provide first evidence that the troublesome symptom of urgency might be particularly modifiable by chronic stress and support the relevance of memory biases in visceroception. These results may help to disentangle the impact of chronic stress on altered visceroception in disturbances of gut-brain communication.

From gut feelings to memories of visceral pain

“…Results supported that chronic stress not only increased the feeling of defecatory urgency induced by rectal distensions as a particularly troublesome visceral symptom with a profound emotional dimension but was also associated with a memory bias for visceral sensations. Specifically, highly stressed individuals recalled more intense feelings of urgency than participants reporting low levels of stress, as well as relative to their initial perception (Icenhour et al, 2020). Together, these findings lend further support to the notion that persisting interoceptive hypervigilance may be distinctly shaped not only by the salience of visceral pain (Koenen et al, 2018) but also by acute and chronic stress.…”

“…Whether chronic stress impacts pain-related emotional learning and memory remains to be elucidated. First evidence of chronic stress as a possible moderator of memory processes in the context of visceroception, however, was recently established in a study elucidating the putative link between perceived chronic stress burden and various facets of visceroception in a large sample of healthy men and women (Icenhour et al, 2020). Results supported that chronic stress not only increased the feeling of defecatory urgency induced by rectal distensions as a particularly troublesome visceral symptom with a profound emotional dimension but was also associated with a memory bias for visceral sensations.…”

Associative learning and extinction of conditioned threat predictors across sensory modalities

“…Our findings support that interoceptive threat predictors may more readily evoke conditioned fear, which could drive the transition from acute to chronic pain as well as symptom chronicity, especially in vulnerable individuals. Furthermore, the risk for impaired extinction efficacy and relapse phenomena may be more pronounced in the context of aversive interoceptive signals, especially in combination with stress 83 , 85 , which demonstrably amplifies visceral nocebo effects 86 , and may contribute to a negative recall bias about aversive visceral experiences 87 . Given the evidence supporting altered extinction learning in patients with chronic pain, including IBS 77 , 78 , translational research in clinical populations is urgently needed.…”

Altered Brain Structure in Chronic Visceral Pain: Specific Differences in Gray Matter Volume and Associations With Visceral Symptoms and Chronic Stress

“…In addition, the present study is the first to investigate whether structural brain measures are related to chronic stress in patients with chronic visceral pain. This question arises given the broad role of stress and stress mediators in normal visceroception ( 50 ), visceral pain sensitivity ( 3 ), visceral pain modulation ( 69 ), and altered brain processing of acute visceral pain in IBS ( 70 ). Even more importantly, stress shapes GI symptom experience and disease course both in IBS ( 71 , 72 ) and IBD ( 37 , 38 ), and is incorporated in treatment approaches in both conditions ( 73 , 74 ).…”

“…Likert-scale response options are “never” (0), “rarely” (1), “sometimes” (2), “often” (3), and “very often” (4), with a total score ranging from 0 to 48, and higher scores indicating greater perceived presence and frequency of chronic stressors. Note that we chose this questionnaire specifically for its applicability not only to research in clinical populations but also in healthy volunteers, expanding on our early work on the role of chronic stress in the context of visceral pain ( 50 ).…”