Involvement of the hypothalamus–raphe–spinal defecation center axis in stress-induced defecation in rats

Abstract Stress-induced defecation disorders, such as irritable bowel syndrome (IBS), are widespread. However, the pathophysiology of these disorders remains unclear. While the vagus nerve has been the primary focus of research on the brain‒gut axis, this nerve poorly innervates the distal colon and rectum. Here we provide evidence that the hypothalamus‒raphe‒spinal cord‒pelvic nerve pathway mediates stress-induced defecation in rats. We used viral tracing, pharmacological, and chemogenetic approaches to show that hypothalamic neurons projecting to the raphe nucleus activate descending serotonergic neurons probably via oxytocinergic signaling, thereby stimulating colorectal motility through the pelvic nerves. Inhibiting this pathway suppresses stress-induced defecation. These findings highlight the role of the hypothalamus‒raphe‒spinal defecation center axis in transmitting psychological stress to the colorectum and offer new insights into the pathophysiology of IBS.