Neuropeptides
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Nitric oxide (NO) donors induce delayed headaches in migraineurs. In a corresponding rat model NO donors cause delayed ongoing activity in central trigeminal neurons which process intracranial afferent input. Cellular models indicate that NO may increase the release or production of calcitonin gene-related peptide (CGRP), a key mediator in primary headaches. ⋯ The present data suggest that prolonged increase in NO levels facilitates stimulated CGRP release from trigeminal ganglion neurons. The underlying mechanism appears to be independent of the cGMP pathway and not to interact with CGRP in the trigeminal ganglion. Delayed headaches induced by NO may change CGRP or CGRP-receptor expression.