Cortisol affects pain sensitivity and pain-related emotional learning in experimental visceral but not somatic pain: a randomized controlled study in healthy men and women

Abstract

Despite growing interest in the role of stress mediators in pain chronicity, the effects of the stress hormone cortisol on acute pain remain incompletely understood. In a randomized, double-blind, placebo-controlled study with N = 100 healthy volunteers, we tested the effects of oral hydrocortisone (20 mg) in 2 widely used pain models for the visceral and somatic modality. Salivary cortisol was increased in the hydrocortisone group (time × group: P < 0.001). For the visceral modality, assessed using pressure-controlled rectal distensions, hydrocortisone decreased the pain threshold from before to after treatment (time × group: P = 0.011), an effect primarily driven by women (time × sex: P = 0.027). For the somatic modality, cutaneous heat pain thresholds remained unaffected by hydrocortisone. Hydrocortisone did not alter perceived pain intensity or unpleasantness of either modality. Conditioned pain-related fear in response to predictive cues was only observed for the visceral modality (time × modality: P = 0.026), an effect that was significantly reduced by hydrocortisone compared with placebo (time × group: P = 0.028). This is the first psychopharmacological study to support that acutely increased cortisol enhances pain sensitivity and impairs pain-related emotional learning within the visceral, but not the somatic pain modality. Stress-induced visceral hyperalgesia and deficits in emotional pain-related learning could play a role in the pathophysiology of chronic visceral pain.

Are there sex differences in visceral sensitivity in young healthy men and women?

“…Studies were conducted in the same experimental setting and with identical methodology for visceral sensitivity testing (see below). Participants for both studies had been recruited via local advertisement using the same inclusion and exclusion criteria for participation in a study on effects of stress or relaxation and on effects of oral hydrocortisone on visceral pain . Please note that visceral sensitivity measures used herein were acquired in both studies before volunteers were randomized to subsequent experimental manipulations (ie, they constituted baseline measures in the primary studies).…”

“…Participants for both studies had been recruited via local advertisement using the same inclusion and exclusion criteria for participation in a study on effects of stress or relaxation 27,28 and on effects of oral hydrocortisone on visceral pain. 29 Please note that visceral sensitivity measures used herein were acquired in both studies before volunteers were randomized to subsequent experimental manipulations (ie, they constituted baseline measures in the primary studies). Thus, results reported herein are independent of the experimental manipulations conducted in the primary studies.…”

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

“…As a crucial psychological factor, stress plays a broad role in disorders of disturbed gut-brain interactions (4)(5)(6). This has most clearly been underscored by evidence that acute stress or stress mediators of the hypothalamus-pituitary-adrenal (HPA) axis increase visceral sensitivity and neural processing of visceral stimuli in patients (7) but also in healthy volunteers (8). Chronic stress burden has been identified as an important risk factor for disease onset (9), and for the exacerbation of GI symptoms, particularly of visceral pain in patients with IBS (10,11).…”

“…Building on our earlier work on the modulation of visceroception by acute stress and stress mediators (7,8,16), we herein aimed to elucidate the putative role of chronic stress in different clinically-relevant facets of normal visceroception.…”

“…This was accomplished given evidence that retrospective overall symptom ratings may be more susceptible to psychological modulation, especially in patients with IBS (18). Given our interest in visceral pain-related memory effects (8,(19)(20)(21)(22), together with evidence supporting the role of reporting bias in IBS (23), we introduced a new "memory bias" measure. This measure was based on the difference between perceptual ratings of individual distensions and retrospective overall ratings, the former being presumably more reflective of sensory-discriminative facts of visceroception, the latter possibly more prone to psychological modulation, both with relevance to collective symptom reporting in experimental and clinical trials as well as clinical practice.…”