Abstract
BackgroundRecent work, both clinical and experimental, suggests that the hypothalamic hormone oxytocin (OT) and its receptor (OTR) may be involved in migraine pathophysiology.In order to better understand possible central actions of OT in migraine/headache pathogenesis, we mapped the distribution of OT and OTR in nerve cells and fibers in rat brain with a focus on areas related to migraine attacks and/or shown previously to contain calcitonin gene related peptide (CGRP), another neuropeptide involved in migraine.MethodsDistribution of OT and OTR in the adult, rat brain was qualitatively examined with immunohistochemistry using a series of well characterized specific antibodies.ResultsAs expected, OT was extensively localized in the cell somas of two hypothalamic nuclei, the supraoptic (SO or SON) and paraventricular nuclei (Pa or PVN). OT also was found in many other regions of the brain where it was localized mainly in nerve fibers. In contrast, OTR staining in the brain was mainly observed in cell somas with very little expression in fibers. The most distinct OTR expression was found in the hippocampus, the pons and the substantia nigra. In some regions of the brain (e.g. the amygdala and the hypothalamus), both OT and OTR were expressed (match). Mismatch between the peptide and its receptor was primarily observed in the cerebral and cerebellar cortex (OT expression) and hippocampus (OTR expression).ConclusionsWe compared OT/OTR distribution in the CNS with that of CGRP and identified regions related to migraine. In particular, regions suggested as “migraine generators”, showed correspondence among the three mappings. These findings suggest central OT pathways may contribute to the role of the hypothalamus in migraine attacks.
Highlights
Oxytocin (OT) is a nine amino acid peptide structurally similar to peptide arginine vasopressin, an antidiuretic hormone, which differs from OT in two of the nine amino acid residues
We have compared this distribution with brain areas identified in imaging studies of humans experiencing a migraine attack [27] (Fig. 1a)
We have correlated our findings with that from our recent study on CNS localization of calcitonin gene related peptide (CGRP), another neuropeptide associated with migraine pathophysiology [25] (Fig. 1b)
Summary
Oxytocin (OT) is a nine amino acid peptide (nonapeptide) structurally similar to peptide arginine vasopressin, an antidiuretic hormone, which differs from OT in two of the nine amino acid residues. These two hormones exhibit in their structure pronounced evolutionary stability [1]. A steadily increasing number of publications on the molecular, physiological, pharmacological, and behavioral significance of OT, the underlying neuroanatomical and neurochemical basis have been studied to a much lesser extent. This is especially true for OT projections within brain [10]. In order to better understand possible central actions of OT in migraine/headache pathogenesis, we mapped the distribution of OT and OTR in nerve cells and fibers in rat brain with a focus on areas related to migraine attacks and/or shown previously to contain calcitonin gene related peptide (CGRP), another neuropeptide involved in migraine
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