Expression of vasopressin and its receptors in migraine-related regions in CNS and the trigeminal system: influence of sex.

Hypothalamus is a key region in migraine attacks. In addition, women are disproportionately affected by migraine. The calcitonin gene-related peptide (CGRP) system is an important key player in migraine pathophysiology. CGRP signaling could be a target of hormones that influence migraine. Our aim is to identify the expression of vasopressin and its receptors in the brain and in the trigeminovascular system with focus on the migraine-related regions and, furthermore, to examine the role of sex on the expression of neurohormones in the trigeminal ganglion. Rat brain and trigeminal ganglia were carefully harvested, and protein and mRNA levels were analyzed by immunohistochemistry and real-time PCR, respectively. Vasopressin and its receptors immunoreactivity were found in migraine-related areas within the brain and, in the trigeminal ganglion, predominantly in neuronal cytoplasm. There were no differences in the number of positive immunoreactivity cells expression of CGRP and vasopressin in the trigeminal ganglion between male and female rats. In contrast, the number of RAMP1 (CGRP receptor), oxytocin (molecular relative to vasopressin), oxytocin receptor and vasopressin receptors (V1aR and V1bR) immunoreactive cells were higher in female compared to male rats. Vasopressin and its receptors mRNA were expressed in both hypothalamus and trigeminal ganglion; however, the vasopressin mRNA level was significantly higher in the hypothalamus. A better understanding of potential hormonal influences on migraine mechanisms is needed to improve treatment of female migraineurs. It is intriguing that vasopressin is an output of hypothalamic neurons that influences areas associated with migraine. Therefore, vasopressin and the closely related oxytocin might be important hypothalamic components that contribute to migraine pathophysiology.