ABSTRACT
This study examines the influence of body mass index (BMI) on the relationship between quantitative sensory testing (QST) measures and clinical characteristics in fibromyalgia syndrome (FMS). Utilizing BMI as a categorical covariate (≥25 or ≥30kg/m²) in associations between QST metrics (Pain-60, conditioned pain modulation [CPM], and temporal summation of pain [TSP]) and FMS clinical features, we explored BMI's role as both a confounder (change-in-estimate criterion - change equal or higher than 10%) and effect modifier (interaction term). Significant interactions revealed overweight/obese BMI as a modifier in the relationship between CPM and both depression and symptom impact, with a homeostatic relationship between better clinical profile and pain inhibitory response observed solely in the normal weight group. Similar results were found for Pain-60 and depression. Additionally, BMI ≥30kg/m² modified TSP's effect on pain, demonstrating lower pain with increased TSP, exclusively in the non-obese group. This study highlights the significant role of BMI in moderating the relationships of important pain inhibitory control processes and pain intensity, depression, and the overall impact of FMS symptoms. Our results suggest that high BMI states disrupt the homeostatic effects of pain inhibition, reducing its salutogenic response in FMS participants. We discuss the mechanistic and therapeutic implications of targeting BMI in FMS clinical trials and the potential impact of this important relationship. PERSPECTIVE: This investigation highlights the disruptive influence of high BMI on pain inhibitory control in fibromyalgia, unbalancing clinical symptoms such as pain and depression. It underscores the necessity of integrating BMI considerations into therapeutic approaches to enhance pain management and patient outcomes.
ABSTRACT
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.