Recent theories have suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor. The present study examined the associations between basal levels of cortisol collected over seven consecutive days, the hippocampal volumes and brain activation to thermal stimulations administered in 16 patients with chronic back pain and 18 healthy control subjects. Results showed that patients with chronic back pain have higher levels of cortisol than control subjects. In these patients, higher cortisol was associated with smaller hippocampal volume and stronger pain-evoked activity in the anterior parahippocampal gyrus, a region involved in anticipatory anxiety and associative learning. Importantly, path modelling-a statistical approach used to examine the empirical validity of propositions grounded on previous literature-revealed that the cortisol levels and phasic pain responses in the parahippocampal gyrus mediated a negative association between the hippocampal volume and the chronic pain intensity. These findings support a stress model of chronic pain suggesting that the sustained endocrine stress response observed in individuals with a smaller hippocampii induces changes in the function of the hippocampal complex that may contribute to the persistent pain states.

No abstract

No 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.