title: Sex dimorphism in a mediatory role of the posterior midcingulate cortex in the association between anxiety and pain sensitivity.
abstract: Behavioral studies found greater pain sensitivity in females that vanishes fully or partially when controlling for the emotional state. Furthermore, pain-related brain activation hints at the role of limbic structures in sex differences in pain processing. We aimed to investigate the role of pain-related limbic structures in mediating the relation between subjects' affective state (i.e., anxiety) and pain. Contact heat-evoked potentials (CHEPs) were recorded in 26 healthy subjects (13 males) simultaneously with innocuous (42 °C) baseline and target noxious (52 °C) series of stimuli administered to the left non-dominant volar forearm. The N2 and P2 components were analyzed, and their generators' activity was estimated using standardized low-resolution brain electromagnetic tomography. Thereafter, structural equation modeling (SEM) was applied separately for females and males, examining the mediatory role of the CHEPs' limbic structures generators [posterior midcingulate cortex (pMCC), insula, amygdala, and hippocampus] in the anxiety-pain sensitivity association. Females exhibited greater P2 amplitudes that were highly associated with larger pMCC activity (r = 0.910, p < 0.001). This correlation was also evident in males, though with less strength (r = 0.578, p = 0.039). Moreover, the P2 amplitudes were associated both in females (r = 0.645, p = 0.017) and males (r = 0.608, p = 0.028) with the activity of the amygdala\hippocampus\insula. SEM revealed that the relationship between state anxiety and pain ratings was only in females fully mediated via the effect of the pMCC on the P2 amplitude. These findings suggest that sexual dimorphism in anxiety-related brain activity may explain the differences found in CHEPs and the sex-related association between anxiety and pain.
authors.affiliation: Department of Psychology, University of Haifa, Haifa, Israel.
authors.forename: Lee-Bareket
authors.initials: LB
authors.lastname: Kisler
authors.affiliation: Laboratory of Clinical Neurophysiology, Technion Faculty of Medicine, Haifa, Israel.|Department of Neurology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Granovsky
authors.affiliation: Department of Neurology, Rambam Health Care Campus, Haifa, Israel.|Department of Neurosurgery, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Sinai
authors.affiliation: Department of Neurology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Elliot
authors.initials: E
authors.lastname: Sprecher
authors.affiliation: Department of Psychology, University of Haifa, Haifa, Israel.
authors.forename: Simone
authors.initials: S
authors.lastname: Shamay-Tsoory
authors.affiliation: Department of Physical Therapy, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel. ifogel@univ.haifa.ac.il.
authors.forename: Irit
authors.initials: I
authors.lastname: Weissman-Fogel
mesh_terms: D000293:Adolescent; D000328:Adult; D001007:Anxiety / Q000473:pathology*; D001931:Brain Mapping; D058443:Catastrophization; D002540:Cerebral Cortex / Q000503:physiopathology*; D004569:Electroencephalography; D005073:Evoked Potentials, Somatosensory / Q000502:physiology*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000473:pathology* / Q000523:psychology; D017288:Pain Threshold / Q000502:physiology; D011601:Psychophysics; D012727:Sex Characteristics; D011795:Surveys and Questionnaires; D055815:Young Adult
keywords: Contact heat-evoked potentials (CHEPs); Midcingulate cortex; Pain psychophysics; Sex differences; Standardized low-resolution brain electromagnetic tomography (sLORETA); Structural equation modeling (SEM)