Cyclic vomiting syndrome (CVS) is the most severe recurrent vomiting disorder in humans and is more prevalent than previously appreciated (1 in 50 school-aged children). Although the pathogenesis remains unknown, corticotropin-releasing factor (CRF) is a tenable candidate brain-gut neuroendocrine mediator of vomiting in CVS. CRF has a well-established role in inducing gastric stasis and vomiting in animals and its resulting behavioral, autonomic, endocrine effects resemble those clinical features seen in CVS. The model of CRF-induced emeses may explain the antiemetic utility of dexamethasone during chemotherapy-induced vomiting and migraine headaches. We hypothesize that systemic CRF levels and hypothalamic-pituitary-ad renal (HPA) axis activity are heightened during episodes of CVS and migraine headache especially in those who experience concomitant nausea and vomiting. To provide direct clinical evidence of involvement of CRF pathways in CVS and migraine, we will examine CRF and HPA axis activation (ACTH, cortisol, catecholamines) in subjects with CVS, migraine headaches and controls under three conditions including: 1) when well (i.e. in between episodes), 2) during acute episodes of cyclic vomiting or migraine headaches treated with a saline placebo, and, 3) during acute episodes of cyclic vomiting or migraine headaches in which CRF is treated by dexamethasone. Under each condition, we will establish the diurnal variation of CRF and HPA axis activity and compare them to pediatric controls, both healthy and with non-CVS vomiting (gastroenteritis). In a randomized, double blind, cross-over design, we will examine the effect of dexamethasone on CRF and HPA axis activity, objective signs and subjective GI and migraine headache symptoms. CVS and migraine headaches may ultimately both be disorders involving dysregulation of CRF pathways.
| Li, B U; Misiewicz, Larry (2003) Cyclic vomiting syndrome: a brain-gut disorder. Gastroenterol Clin North Am 32:997-1019 |
