Posted on 13-07-2022

Sex-dependent differences in connectivity between the amygdala and cognitive-affective processing regions in adolescents with chronic neuropathic pain (NeuP)

Chronic neuropathic pain (NeuP) in children and adolescents is thought to occur through a different mechanism than in adults. While neuroimaging studies have focused largely on understanding chronic pain in pediatric populations that have complex regional pain syndrome, little is known about the neural mechanisms underlying pediatric peripheral NeuP.

Recent work has investigated brain network connectivity using resting state functional connectivity (rsFC) in order to observe intrinsic brain states and possible abnormalities in those with chronic pain. The amygdala is a limbic brain region involved in the affective dimension of pain and its modulation. Studies in adults with chronic pain have reported higher rsFC than pain-free individuals of the amygdala with corticolimbic areas involved in cognitive-affective control, memory, and sensory-discriminative processing, as well as with regions of the frontoparietal network. The amygdala is also sensitive to changes in sex hormones, especially during adolescence, but it is unknown whether adolescents have altered connectivity with the amygdala, and if these connectivity patterns are generalized across the sexes and pediatric chronic pain conditions like NeuP.

In this study, UTCSP scientist Dr. Massieh Moayedi and colleagues investigated amygdala rsFC in male and female adolescents with chronic NeuP. It was hypothesized that rsFC of the amygdala to nociceptive, cognitive-affective, and pain modulatory areas would be different in adolescents with chronic NeuP compared to healthy individuals. It was also hypothesized that differences in connectivity would be related to measures of pain intensity and pain catastrophizing.

Seventeen adolescents aged 11-18 years with chronic NeuP underwent a single session of fMRI scans. All participants used a visual analog scale to report their average and worst pain intensity over the previous week. Each participant completed the child’s version of the pain catastrophizing scale. Patient data were compared with healthy adolescents’ scans.

The authors found that those with NeuP in comparison to the controls showed stronger negative rsFC between the right amygdala and the right dorsolateral prefrontal cortex (dlPFC), and stronger positive rsFC between the right amygdala and the left angular gyrus (AG). The dlPFC and AG are regions of the cognitive-control network (frontoparietal regions), suggesting that there is an impact on cognitive-affective processing in the NeuP group. More specifically, in males, lower pain intensity was found to be correlated with stronger negative amygdala – dlPFC rsFC. In females, there was a correlation between lower pain intensity and stronger positive amygdala – AG rsFC. These findings suggest that differences in limbic pain modulatory circuits exist in adolescents with NeuP, where amygdala rsFC relationships are inhibitory in nature and sex-dependent. Future work should continue to investigate sex-differences displayed in underlying brain mechanisms of adolescents with NeuP.

To read more about this study, please see:

Verriotis, M., Sorger, C., Peters, J., Ayoub, L. J., Seunarine, K. K., Clark, C. A., Walker, S. M., & Moayedi, M. (2022). Amygdalar Functional Connectivity Differences Associated With Reduced Pain Intensity in Pediatric Peripheral Neuropathic Pain. Frontiers in Pain Research, 3. https://www.frontiersin.org/articles/10.3389/fpain.2022.918766

Written by: Vaidhehi Veena Sanmugananthan

Edited by: Georgia Hadjis