Altered parasympathetic outflow and central sensitization response to continuous pain in cyclic vomiting syndrome: a functional magnetic resonance imaging study

Cyclic vomiting syndrome (CVS) is a disorder of brain-gut interaction characterized by recurrent episodes of nausea and vomiting interspersed with asymptomatic periods and associated with autonomic nervous system dysfunction. We examined the dysautonomic response to noxious stimuli for patients with CVS using our previously validated approach to integrate peripheral autonomic outflow metrics, temporal summation of pain, and brain functional MRI (fMRI). Blood oxygen level-dependent (BOLD) fMRI and ECG were acquired from patients with CVS and healthy adults during both a rest condition and a sustained cuff pressure-pain stimulus at the leg. After the latter scan, participants rated pain for the first, middle, and last 2 min to calculate temporal summation. During sustained pain, patients, relative to healthy controls, exhibited greater reduction in heart rate variability within the high-frequency range (HF-HRV) and reduced anticorrelation between HF-HRV and fMRI signal in the anterior insula, pregenual anterior cingulate cortex, and ventrolateral and dorsolateral prefrontal cortex. Compared with healthy adults, patients also exhibited increasing pain intensity over the course of sustained cuff pressure. For healthy adults, seed-based functional connectivity analysis revealed pain sensitization correlated with pain-induced increases in connectivity between primary somatosensory cortex and regions of interest in both left anterior insula/posterior orbitofrontal cortex and right presupplementary motor area. These correlations were not seen in CVS, thus supporting a conclusion of altered central coding of nociceptive stimuli and autonomic responsivity of patients with CVS in key brain regions implicated in autonomic control and interoception.<b>NEW & NOTEWORTHY</b> Patients with cyclic vomiting syndrome exhibit multiple alterations in central function in response to a sustained pressure-pain stimulus, including altered high-frequency heart rate variability and associated changes in BOLD fMRI signal in key areas of the central autonomic and interoceptive networks, as well as abnormal temporal summation of pain associated with altered connectivity patterns between the primary somatosensory cortex and key regions associated with interoception.