Oxytocin as a regulatory neuropeptide in the trigeminovascular system: localization, expression and function of oxytocin and oxytocin receptors

Abstract

Recent clinical findings show oxytocin (OT) inhibits migraine headache, suggesting an unexpected role of this neuropeptide/hormone in trigeminal pain signaling. Here we show OT receptors (OTR) are extensively expressed throughout the rat trigeminovascular system. Using immunohistochemistry and qPCR, we found OTR expression in trigeminal ganglia (TG), in particular, in a large portion of the A‐delta sensory neurons and fibers. OTR also was expressed in the central target of TG afferents, the trigeminal nucleus caudalis. A small number of C‐fiber sensory neurons in the TG expressed OTR; which was colocalized with the neuropeptide CGRP (calcitonin gene related peptide). However, OT had no effect on K+‐evoked CGRP release from either isolated TG or TG afferents in the dura mater. Another peripheral TG target, the cranial arteries, were found to constrict in response to OT in vitro; an effect blocked by the OTR antagonist L368899. OT immunoreactivity was found in TG satellite glial cells but OT mRNA was undetectable in TG. Thus OT from the circulation most likely acts on OTR in the TG to affect pain transmission. These effects may help explain hormonal influences in migraine and offer a novel target for treatment.Support or Funding InformationLundbeck Foundation and Swedish Medical Research Council