Acute Stress Contributes to Individual Differences in Pain and Pain-Related Brain Activity in Healthy and Chronic Pain Patients

Abstract

Individual differences in pain sensitivity and reactivity are well recognized but the underlying mechanisms are likely to be diverse. The phenomenon of stress-induced analgesia is well documented in animal research and individual variability in the stress response in humans may produce corresponding changes in pain. We assessed the magnitude of the acute stress response of 16 chronic back pain (CBP) patients and 18 healthy individuals exposed to noxious thermal stimulations administered in a functional magnetic resonance imaging experiment and tested its possible contribution to individual differences in pain perception. The temperature of the noxious stimulations was determined individually to control for differences in pain sensitivity. The two groups showed similar significant increases in reactive cortisol across the scanning session when compared with their basal levels collected over 7 consecutive days, suggesting normal hypothalamic-pituitary-adrenal axis reactivity to painful stressors in CBP patients. Critically, after controlling for any effect of group and stimulus temperature, individuals with stronger cortisol responses reported less pain unpleasantness and showed reduced blood oxygenation level-dependent activation in nucleus accumbens at the stimulus onset and in the anterior mid-cingulate cortex (aMCC), the primary somatosensory cortex, and the posterior insula. Mediation analyses indicated that pain-related activity in the aMCC mediated the relationship between the reactive cortisol response and the pain unpleasantness. Psychophysiological interaction analysis further revealed that higher stress reactivity was associated with reduced functional connectivity between the aMCC and the brainstem. These findings suggest that acute stress modulates pain in humans and contributes to individual variability in pain affect and pain-related brain activity.

Mediators and Moderators of Chronic Pain Outcomes in an Online Self-Management Program

“…In this analysis, stress mediated the relationship between painACTION.com intervention and pain severity. The link between pain and stress has long been supported in the literature, 48,49 to the extent that cognitive-behavioral stress-management has been used as a treatment for chronic tension-type headaches. 22 Although not statistically significant, a similar trend was noted for depression.…”

Psychosocial versus physiological stress — Meta-analyses on deactivations and activations of the neural correlates of stress reactions

“…Second, pain processing is easily manipulated and therefore most frequently investigated in neuroimaging environments. Handling pain integrates sensory as well as affective processing (Price, 2000) and it has an arousing effect, increasing cortisol release and negative affect (Rainville, 2002; Vachon-Presseau et al, 2013a; Zubieta and Stohler, 2009). In neuroimaging environments, acute pain is induced by paradigms such as electric shocks or ice cold water which are known to increase cortisol and noradrenalin release.…”

Psychosocial Stress-Induced Analgesia: An Examination of Effects on Heat Pain Threshold and Tolerance and of Neuroendocrine Mediation

“…It has been widely reported in animals [1,2] and to a lesser and more heterogeneous extent in humans [for examples, see [3,4,5,6,7,8,9]]. In humans, SIA has been elicited using physical [10], psychological [7,11], and psychosocial [6] stressors.…”

“…It is modulated by opioid [9,20] and non-opioid mechanisms involving monoamines [21,22] as well as endocrine processes [23] involved in the regulation of stress. While the involvement of the corticotropin-releasing factor as well as glucorticosteroids has been found to be important in the development of SIA in animals [23,24,25,26,27,28,29], comparable endocrine evidence in humans is scarce.…”

“…While the involvement of the corticotropin-releasing factor as well as glucorticosteroids has been found to be important in the development of SIA in animals [23,24,25,26,27,28,29], comparable endocrine evidence in humans is scarce. On the one hand negative associations between cortisol and pain perception have been reported with regard to cortisol and pain responses to the cold pressor test as well as to noxious thermal stimulations [9,30]. On the other hand, cortisol responses did not affect the association between the effects of stress and pain rating in the cold pressor test [6].…”