Investigating the associations of 2126 cortical structural alterations with chronic pain onset
Poster No:
2038
Submission Type:
Abstract Submission
Authors:
Wang Xiuzhi1, Liang Meng1
Institutions:
1Tianjin Medical Univesity, 天津市, China
First Author:
Co-Author:
Introduction:
Chronic pain is a prevalent condition that imposes substantial personal and societal burdens. Understanding the brain mechanisms underlying individual susceptibility to chronic pain remains a significant challenge. Previous studies on the brain mechanisms of chronic pain susceptibility have largely focused on specific brain regions or imaging metrics, lacking a comprehensive exploration of the neural underpinnings. Moreover, the causal relationship between brain alterations and chronic pain remains unclear, highlighting the need for more integrative and causally-informed investigations in this field.
Methods:
In this study, we examined the prospective associations between 2126 cortical structural MRI phenotypes-derived from T1-weighted and diffusion tensor imaging scans-and chronic pain susceptibility in UK Biobank cohort of 5,026 to 5,756 participants. The cortical phenotypes included both macrostructural features (e.g.,surface area, cortical thickness) and microstructural features (e.g., fractional anisotropy, mean diffusivity).We employed general linear models (GLMs) to identify brain structural variations significantly associated with the future onset of chronic pain, as self-reported by participants. Each model controlled for age, sex, age*sex, first 10 genetic PCs, TIV (Total intracranial volume), follow-up, multiple deprivation index (a measure of socioeconomic status), educational attainment, BMI, smoking status, alcoholic drinking status, and ever seen a doctor for nervousness, anxiety, tension, or depression that can be potential confounders. P values were corrected by the number of effective independent test.
In addition, Mendelian randomization was performed to identify potential causal relationship between brain IDPs and chronci pain. Be specific, instrumental variants (IVs) were defined as SNPs associated with the exposure at P<1*10−5 , ensuring sufficient strength across all exposures-a threshold commonly used in previous MR studies. Independent IVs were identified through LD clumping with a window size of 10,000 kb and an LD threshold of r²<0.001, ensuring that the selected IVs were not in high LD with one another. Subsequently, the effect alleles of the IVs were harmonized between the exposure and outcome datasets, with palindromic IVs excluded to avoid strand ambiguity. The F-statistics for all IVs were calculated, and IVs with F-statistic values less than 10 were removed to minimize the risk of weak instrument bias. Additionally, Steiger's test was performed to exclude IVs that exhibited a stronger correlation with the outcome than the exposure. Finally, outliers were identified and excluded using the RadialMR method. P values were corrected by the number of effective independent test.
In addition, Mendelian randomization was performed to identify potential causal relationship between brain IDPs and chronci pain. Be specific, instrumental variants (IVs) were defined as SNPs associated with the exposure at P<1*10−5 , ensuring sufficient strength across all exposures-a threshold commonly used in previous MR studies. Independent IVs were identified through LD clumping with a window size of 10,000 kb and an LD threshold of r²<0.001, ensuring that the selected IVs were not in high LD with one another. Subsequently, the effect alleles of the IVs were harmonized between the exposure and outcome datasets, with palindromic IVs excluded to avoid strand ambiguity. The F-statistics for all IVs were calculated, and IVs with F-statistic values less than 10 were removed to minimize the risk of weak instrument bias. Additionally, Steiger's test was performed to exclude IVs that exhibited a stronger correlation with the outcome than the exposure. Finally, outliers were identified and excluded using the RadialMR method. P values were corrected by the number of effective independent test.
Results:
Our regression analyses results reveal that reduced cortical surface area in the parsopercularis, a region traditionally involved in pain processing, emotional regulation, and pain-related cognition, is significantly associated with an increased risk of developing chronic pain (T=-4.214, P=2.55E-05). In addition, the Mendelian randomization indicate a significant causal effect of the surface area of parsopercularis cortex (BA 44) on chronic pain(OR=0.91, P of IVW=1.91E-2).
·Association analyses of 2126 brain structural phenotypes with chronic pain
·Significant causal effects of cortical MRI phenotypes on chronic pain
Conclusions:
These findings suggest that individual differences in the prefrontal operculum may play a critical role in determining vulnerability to chronic pain, offering potential insights for personalized pain management strategies.
Modeling and Analysis Methods:
Univariate Modeling 2
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral 1
Keywords:
Cortex
MRI
Pain
1|2Indicates the priority used for review