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

Emotions have powerful effects on pain perception. However, the brain mechanisms underlying these effects remain largely unknown. In this study, we combined functional cerebral imaging with psychophysiological methods to explore the neural mechanisms involved in the emotional modulation of spinal nociceptive responses (RIII-reflex) and pain perception in healthy participants. Emotions induced by pleasant or unpleasant pictures modulated the responses to painful electrical stimulations in the right insula, paracentral lobule, parahippocampal gyrus, thalamus, and amygdala. Right insula activation covaried with the modulation of pain perception, consistent with a key role of this structure in the integration of pain signals with the ongoing emotion. In contrast, activity in the thalamus, amygdala, and several prefrontal areas was associated with the modulation of spinal reflex responses. Last, connectivity analyses suggested an involvement of prefrontal, parahippocampal, and brainstem structures in the cerebral and cerebrospinal modulation of pain by emotions. This multiplicity of mechanisms underlying the emotional modulation of pain is reflective of the strong interrelations between pain and emotions, and emphasizes the powerful effects that emotions can have on pain. Descending pain-modulatory pathways originate from various cerebral structures involved in emotions (6-8) and sensorimotor functions (9). These regions are thought to affect spinal nociception through their projections to several brainstem structures, including the periaqueductal gray matter (PAG), rostroventral medulla (RVM), dorsolateral pontine tegmentum (DLPT), and nucleus cuneiformis (NCF) (10). All of these structures are thus potential cerebral sources of the descending modulation of pain by emotions. In turn, the modulation of spinal activity is expected to affect the transmission of nociceptive signals and the response of their target brain regions through the multiple ascending pathways. However, the important interconnectivity between emotional brain networks and areas implicated in the affective dimension of pain suggests that additional supraspinal mechanisms might also contribute to the emotional modulation of pain experiences. Among the potential cortical candidates, the anterior cingulate cortex (ACC) (11) and the insula (12) are well positioned to contribute to the emotional modulation of pain.Whereas the ACC appears to be involved in the motoric and motivational aspects of pain and emotions, the insula is thought to generate subjective interoceptive feelings as a result of the gradual posterior-to-anterior integration of primary interoceptive information with contextual emotional and cognitive information (12).The cerebral correlates of the emotional modulation of pain perception have been explored in two brain imaging studies. In one study, pain-related activation in the entorhinal cortex was increased by expectation-induced anticipatory anxiety of a highly painful stimulation (13). Also, the increased activation in the entorhinal...

Facial expression of affective states plays a key role in social interactions. Interestingly, however, individuals differ substantially in their level of expressiveness, ranging from high expressive to stoic individuals. Here, we investigate which brain mechanisms underlie the regulation of facial expressiveness to acute pain. Facial responses, pain ratings, and brain activity (BOLD-fMRI) evoked by noxious heat and warm (control) stimuli were recorded in 34 human volunteers with different degrees of facial expressiveness. Within-subject and between-subject variations in blood oxygenation level-dependent (BOLD) responses were examined specifically in relation to facial responses. Pain expression was inversely related to frontostriatal activity, consistent with a role in downregulating facial displays. More detailed analyses of the peak activity in medial prefrontal cortex revealed negative BOLD responses to thermal stimuli, an effect generally associated with the default mode network. Given that this negative BOLD response was weaker in low expressive individuals during pain, it could reflect stronger engagement in, or reduced disengagement from, self-reflective processes in stoic individuals. The occurrence of facial expressions during pain was coupled with stronger primary motor activity in the face area and-interestingly-in areas involved in pain processing. In conclusion, these results indicate that spontaneous pain expression reflects activity within nociceptive pathways while stoicism involves the active suppression of expression, a manifestation of learned display rules governing emotional communication and possibly related to an increased self-reflective or introspective focus.