The role of pain catastrophizing in modulating irritable bowel syndrome symptoms through brain-spinal cord integration

Irritable bowel syndrome (IBS) is a prevalent disorder characterized by abnormal brain-gut interactions. Notable, psychosocial stressors have been consistently observed to increase susceptibility to additional physical symptoms of IBS. However, the neuropsychological mechanism underlining this disordered top-down control by the central nervous system remains unclear. To address this issue, we investigated gray matter characteristics in the brain and spinal cord of 53 IBS patients and 35 healthy controls (HCs) using simultaneous three-dimensional T1-weighted cortico-spinal imaging. All participants had their IBS symptom severity and pain-related negative emotions quantified using a comprehensive clinical and psychosocial symptom questionnaire battery. We used partial least-squares correlation analysis to assess the associations from complex, heterogeneous variable sets. Our results showed that gut-brain dysregulation may be related to abnormal changes in brain gray matter volumes, particularly in superior frontal gyrus, middle frontal gyrus and precentral gyrus. Mediation analyses indicated that pain catastrophizing is associated with these gray matter abnormalities, which may be linked to more severe physical symptoms of IBS. Additionally, the gray matter properties in segments C5 to C6 of the spinal cord serve as serial mediators in the relationship between the top-down brain control and gut function, influencing abdominal pain severity. Our study provides novel insights into the top-down control mechanisms contributing to IBS symptoms, emphasizing the potential benefits of early intervention for pain catastrophizing. WHAT IS KNOWN: 1. Irritable bowel syndrome is a common disorder characterized by abnormal brain–gut interactions. 2. Many patients of irritable bowel syndrome experience non-painful abdominal discomfort and psychological symptoms. 3. Dysregulated behavioral and psychological responses may then impact spinal dorsal horn neurons, ultimately affecting the enteric nervous system and exacerbating IBS symptoms. 4. Research has predominantly focused on brain sensitization following visceral inflammation or stress, with limited attention given to characterizing the spinal circuits responsible for transmitting visceral sensory information. WHAT IS NEW HERE: 1. Gut-brain dysregulation might cause abnormal changes in brain gray matter volumes, particularly in the superior frontal gyrus, middle frontal gyrus and precentral gyrus. 2. Pain catastrophizing significantly contributes to gray matter abnormalities, which may, in turn, exacerbate the physical symptoms of IBS. 3. The gray matter properties in segments C5-C6 of the spinal cord serve as serial mediators in the relationship between the top-down brain control and gut function, influencing abdominal pain severity.