Jen-I Chen

Cerebral and spinal modulation of pain by emotions

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.

The Stress Model of Chronic Pain: Evidence from Basal Cortisol and Hippocampal Structure and Function in Humans.

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.

Cerebral Regulation of Facial Expressions of Pain

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.

Neural processing of sensory and emotional-communicative information associated with the perception of vicarious pain☆

The specific neural processes underlying vicarious pain perception are not fully understood. In this functional imaging study, 20 participants viewed pain-evoking or neutral images displaying either sensory or emotional-communicative information. The pain images displayed nociceptive agents applied to the hand or the foot (sensory information) or facial expressions of pain (emotional-communicative information) and were matched with their neutral counterparts. Combining pain-evoking and neutral images showed that body limbs elicited greater activity in sensory motor regions, whereas midline frontal and parietal cortices and the amygdala responded more strongly to faces. The pain-evoking images elicited greater activity than their neutral counterparts in the bilateral inferior frontal gyrus (IFG), the left inferior parietal lobule (IPL) and the bilateral extrastriate body area. However, greater pain-related activity was observed in the rostral IPL when images depicted a hand or foot compared to a facial expression of pain, suggesting a more specific involvement in the coding of somato-motor information. Posterior probability maps enabling Bayesian inferences further showed that the anterior IFG (BA 45 and 47) was the only region showing no intrinsic probability of activation by the neutral images, consistent with a role in the extraction of the meaning of pain-related visual cues. Finally, inter-individual empathy traits correlated with responses in the supracallosal mid/anterior cingulate cortex and the anterior insula when pain-evoking images of body limbs or facial expressions were presented, suggesting that these regions regulated the observers affective-motivational response independent from the channels from which vicarious pain is perceived.

Thicker Posterior Insula Is Associated With Disease Duration in Women With Irritable Bowel Syndrome (IBS) Whereas Thicker Orbitofrontal Cortex Predicts Reduced Pain Inhibition in Both IBS Patients and Controls

UNLABELLED Patients with irritable bowel syndrome (IBS) are affected by chronic abdominal pain and show decreased pain inhibition. Moreover, they exhibit differences in brain morphology compared with healthy volunteers. The aim of this study was to examine whether decreased pain inhibition is associated with altered brain morphology in IBS patients. Structural magnetic resonance imaging scans were acquired in 14 female patients with diarrhea-predominant IBS and 14 controls. Pain and anxiety modulation were characterized using electrical stimulation of the sural nerve and heterotopic noxious counterstimulation. IBS patients reported decreased pain inhibition (P = .02) as well as increased shock anxiety, pain catastrophizing, depressive symptoms, and trait anxiety (Ps ≤ .05). IBS patients also showed a thicker right posterior insula (pINS), associated with longer IBS duration (r = .67, P = .02). In addition, thicker right lateral orbitofrontal cortex was strongly associated with less pain inhibition in both IBS patients (r = .70, P = .02) and controls (r = .68, P = .01). Results are consistent with the role of the insula in interoception and pain and suggest that IBS may induce thickening of the pINS. Reduced pain inhibition may further involve a modification of the regulatory influence of the orbitofrontal cortex on pain-related processes. PERSPECTIVE This study investigated the brain morphology of IBS patients. IBS patients showed thicker right pINS, associated with longer disease duration but not with psychological symptoms. This suggests that IBS induces thickening of pINS, which may contribute to its pathophysiology, consistent with the role of the pINS in interoception and pain.

Reduction of physiological noise with independent component analysis improves the detection of nociceptive responses with fMRI of the human spinal cord

The evaluation of spinal cord neuronal activity in humans with functional magnetic resonance imaging (fMRI) is technically challenging. Major difficulties arise from cardiac and respiratory movement artifacts that constitute significant sources of noise. In this paper we assessed the Correction of Structured noise using spatial Independent Component Analysis (CORSICA). FMRI data of the cervical spinal cord were acquired in 14 healthy subjects using gradient-echo EPI. Nociceptive electrical stimuli were applied to the thumb. Additional data with short TR (250 ms, to prevent aliasing) were acquired to generate a spatial map of physiological noise derived from Independent Component Analysis (ICA). Physiological noise was subsequently removed from the long-TR data after selecting independent components based on the generated noise map. Stimulus-evoked responses were analyzed using the general linear model, with and without CORSICA and with a regressor generated from the cerebrospinal fluid region. Results showed higher sensitivity to detect stimulus-related activation in the targeted dorsal segment of the cord after CORSICA. Furthermore, fewer voxels showed stimulus-related signal changes in the CSF and outside the spinal region, suggesting an increase in specificity. ICA can be used to effectively reduce physiological noise in spinal cord fMRI time series.

73 NEURONAL BASE OF THE FACIAL EXPRESSION OF PAIN

of each item to discriminate fibromyalgia and other chronic rheumatologic syndromes. Results: Analysis of the metrologic properties of the FiRST questionnaire allowed to exclude four items from the initial version and identified the 6 most discriminative items. We confirmed that the 6-item FiRST questionnaire has excellent properties to discriminate FMS. Conclusion: FiRST is a new, simple and easy-to-use questionnaire with good sensitivity and specificity to detect patients with FMS. It may help physicians to detect FMS patients, for a better and earlier management both in clinical research and daily practice.

Correction: Test-retest reliability of myelin imaging in the human spinal cord: Measurement errors versus region- and aging-induced variations

[This corrects the article DOI: 10.1371/journal.pone.0189944.].

Brain processing of the temporal dimension of acute pain in short-term memory

Abstract The dynamics of noxious sensation shapes pain perception, yet the memory of the temporal dimension of pain remains almost completely unexplored. Here, brain activity during the memory of pain duration was contrasted with that associated with the memory of pain intensity using functional magnetic resonance imaging and a delayed reproduction task. Participants encoded, maintained during a short delay, and reproduced (1) the “duration” of pain (ie, onset-to-offset), (2) the “dynamics” of pain (ie, evolution of pain over time), or (3) the intensity of pain (ie, control with no explicit temporal processing required). Results show that the inferior frontal gyrus/insula and adjacent striatal structures as well as the supramarginal and middle temporal gyri are activated in the duration task compared to the control intensity task. Specific examination of the memory delay of the duration task further revealed activation in the supramarginal gyrus extending to the parietal operculum (possibly SII) and primary somatosensory cortex (SI). In contrast, the memory delay of the dynamic task involved the bilateral supplementary motor area and the frontoparietal attentional network. Although SI, SII, and insula may contribute to the memory trace of pain sensation, other areas less commonly reported in pain studies are associated with time processing and may therefore contribute to the processing of temporal aspects of pain. Results further suggest a differential role of core timing regions of the brain depending on specific task instructions and attentional allocations to the single dimension of time, as compared to the joint processing of both time and intensity.