The Impact of Obesity as a Peripheral Disruptor of Brain Inhibitory Mechanisms in Fibromyalgia: A Cross-Sectional Study.

Background/Objective: Obesity, characterized by chronic inflammation, may serve as a surrogate marker for more dysfunctional peripheral inflammation, potentially exacerbating FM symptomatology. Given this premise, this study aimed to investigate the effects of obesity as an effect modifier on neural and clinical variables, specifically those indexing pain-compensatory mechanisms in FM symptoms. Methods: A cross-sectional study was conducted with 108 participants who underwent a standardized TMS protocol assessment to measure resting motor threshold (MT), intracortical facilitation (ICF), and intracortical inhibition (ICI). Clinical data were collected using Beck's Depression Index (BDI), PROMIS, the Brief Pain Inventory (BPI), and conditioned pain modulation (CPM). Linear regression models were used to explore the relationship between these variables while examining Body Mass Index (BMI) as a potential effect modifier. If it was found to be a modifier, we stratified the sample into two groups with a BMI cutoff of 30 and performed another regression model within the subgroups. Results: BMI was identified as an effect modifier in the relationships between ICI and BDI, PROMIS fatigue, and CPM and in MT versus CPM. After stratification, non-obese fibromyalgia subjects demonstrated significant correlations between clinical symptoms and CPM and ICI activity. However, these correlations were absent in the obese group, suggesting obesity disrupts pain mechanisms and their compensatory effects. Higher MT values were associated with weaker endogenous pain control, particularly evident in the obese group. Conclusions: Obesity appears to be a significant effect modifier and delineates two patient groups across multiple clinical and neural assessments of fibromyalgia. Additionally, it suggests a role for obesity in exacerbating fibromyalgia symptoms and disrupting physiological pain-inhibitory mechanisms.