Sex-Specific Differences in Brainstem Microstructure in Chronic Visceral Pain
Jennifer Labus, PhD1,2, Chencai Wang,PhD1,3, Priten Vora ,BS 1,2, Cathy Liu, BS1,2, Jean Stains, RN,1,2, Arpana Gupta,PhD,1,2 Emeran Mayer, MD,1,2 Ben Ellingson, PhD,1,3
1G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California Los Angeles; 2UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA; 33Department of Radiological Science, UCLA
Background: Sex-related changes in the neural organization of brainstem nuclei that are critical for processing visceral afferent signaling and descending pain modulation have not been studied in irritable bowel syndrome (IBS). Objective: Perform region of interest (ROI) analysis to test the hypothesis that there are sex differences in the microstructural properties of the locus coeruleus (LC), dorsal (DR) and median raphe (MR) nuclei, parabrachial complex (PBC), and periaqueductal gray (PAG) individuals with IBS. Methods: Diffusion tensor images were obtained in 107 female and 45 male nonobese IBS subjects on a 3T Siemens Trio. The general linear model was applied to test differences in the fractional anisotropy(FA) and mean diffusivity(MD) in ROIs controlling for age and BMI. Independent t-test were used to assess group differences in symptom and psychosocial assessments. Results: Female compared to males were younger (26.7 v 31.87 y) and reported shorter pain duration (8.7 v 12.9y). Females also had greater pain catastrophizing, visceral sensitivity, IBS symptom severity, somatic awareness, and widespread pain (p’s<05). Compared to males, females demonstrated significantly higher FA in the PAG, the primary control center for descending pain modulation, but lower FA in the noradrenergic LC, serotonergic raphe (DR, MR), and the PBC, a major viscerosensory relay center. Females also had lower MD for DR and PAG but higher MD for the MR (cluster-level significance at 5% false discovery rate). Correlation analysis revealed sex-specific associations between the brainstem region microstructure and symptom and psychosocial measures. Conclusion: There are sex differences in the neural organization of brainstem systems that are critical for viscerosensory modulation and descending pain inhibition. In IBS women brainstem nuclei microstructure was associated with IBS-specific symptoms whereas in IBS males the association was with widespread pain. The serotonergic dorsal raphe nucleus appears to contribute most to symptom presentation in women whereas the noradrenergic locus coeruleus has more influence in men.
Breakout Room: Labus, Jen
View Poster: https://uclacns.org/symposium2021/14-labus-jennifer.pdf