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Colocalization of CGRP with 5‐HT1B/1D receptors and substance P in trigeminal ganglion neurons in rats

Vasodilatation in the dura mater has been implicated in migraine pathogenesis. Anti‐migraine triptan drugs block vasodilatation by binding to 5‐HT1B/1D receptors localized on the peripheral sensory terminals and dural blood vessel smooth muscles. Previous studies suggest that calcitonin gene‐related peptide (CGRP) released from Aδ‐fibres plays a more important role than substance P (SP) released from C‐fibres in inducing dural vasodilatation and that one of the antimigraine mechanisms of triptan drugs is inhibiting CGRP release. In the present study, the relationship between CGRP and 5‐HT1B/1D receptors, and between CGRP and SP in the trigeminal ganglion neurons in rats was examined by double immunohistochemical staining. CGRP, 5‐HT1B, 5‐HT1D and SP‐positive trigeminal ganglion neurons were all predominantly small and medium‐sized. In the trigeminal ganglia, ≈ 50% of CGRP‐positive neurons were 5‐HT1B positive. Similarly, ≈ 55% of CGRP‐positive neurons were 5‐HT1D immunoreactive. Approximately 50% of CGRP‐positive neurons were SP‐positive, while 93% of SP‐positive neurons were CGRP‐positive, suggesting that nearly all SP‐positive neurons also contain CGRP. The fibre types of the 5‐HT1B‐ and 5‐HT1D‐positive neurons were further investigated with an antibody against the A‐fibre marker 200‐kDa neurofilaments (NF200). Approximately 46% of the 5‐HT1B‐positive and 43% of the 5‐HT1D‐positive trigeminal ganglion neurons were also NF200 positive, indicating that many A‐fibre trigeminal neurons express 5‐HT1B or 5‐HT1D receptors. These results support the hypothesis that one important action of antimigraine drugs is the inhibition of CGRP release and that Aδ‐fibres may play an important role in migraine pathogenesis.