Sex‐based differences in brain alterations across chronic pain conditions

Abstract

Common brain mechanisms are thought to play a significant role across a multitude of chronic pain syndromes. In addition, there is strong evidence for the existence of sex differences in the prevalence of chronic pain and in the neurobiology of pain. Thus, it is important to consider sex when developing general principals of pain neurobiology. The goal of the current review is to evaluate what is known about sex-specific brain alterations across multiple chronic pain populations. A total of 15 sex difference and 143 single-sex manuscripts were identified out of 412 chronic pain neuroimaging manuscripts. Results from sex difference studies indicate more prominent primary sensorimotor structural and functional alterations in female chronic pain patients compared to male chronic pain patients; differences in the nature and degree of insula alterations, with greater insula reactivity in male patients; differences in the degree of anterior cingulate structural alterations; and differences in emotional-arousal reactivity. Qualitative comparisons of male-specific and female-specific studies appear to be consistent with the results from sex difference studies. Given these differences, mixed-sex studies of chronic pain risk creating biased data or missing important information and single-sex studies have limited generalizability. The advent of large scale neuroimaging databases will likely aid in building a more comprehensive understanding of sex differences and commonalities in brain mechanisms underlying chronic pain.

A transcriptional toolbox for exploring peripheral neuro-immune interactions

“…Regarding sex differences, we would like to stress that the absence of consistent sex differences in our flow and RNA-seq data does not mean that they are not present at lower effect sizes that we likely were not powered to detect. We would also like to emphatically endorse the importance of sex and gender considerations when studying neuro-immune interactions -especially since they are known to play prominent roles in the perception of pain, chronic pain conditions and immune system function [52][53][54][55][56] .…”

Are there sex differences in visceral sensitivity in young healthy men and women?

“…Thus, the major goal for future investigations remains to disentangle the complex factors and their interactions, which contribute to an increased risk for visceral pain chronification in women. This calls for studies combining different lines of research where sex differences have previously been documented, including but not limited to measures of psychological distress, neuroendocrine and immune parameters, as well as of the autonomic and central nervous system . Ultimately, a complex interplay between central and peripheral processes rather than isolated factors is likely to adversely affect brain‐gut interactions, including visceral sensitivity.…”

“…Nevertheless, our recruitment strategy precludes to draw conclusions regarding visceral sensitivity in women with natural 49,50 as well as of the autonomic 51 and central nervous system. 23,25,31,52 Ultimately, a complex interplay between central and peripheral processes rather than isolated factors is likely to adversely affect brain-gut interactions, including visceral sensitivity.…”

Sex Differences in Trauma-Related Psychopathology: a Critical Review of Neuroimaging Literature (2014–2017)

“…Centrality of the amygdala was associated with physical symptoms for all, and segregation of the insula was correlated with higher somatization among males only, with a non-significant but negative relationship among females. Decreased centrality of the insula and pregenual ACC (pgACC; involved in regulatory functions) associated with increased general early adversities in females [71]. Thus, the association between centrality of salience hubs and childhood adversities appeared to be reversed in adult males and females, as was the relationship between segregation of insula and physical symptoms.…”