5-HT1D Receptor Immunoreactivity in the Sphenopalatine Ganglion: Implications for the Efficacy of Triptans in the Treatment of Autonomic Signs Associated With Cluster Headache

Objective.— To determine if 5‐HT1D receptors are located in the sphenopalatine ganglion. Background.— While the 5‐HT1D receptor has been described in sensory and sympathetic ganglia in the head, it was not known whether they were also located in parasympathetic ganglia. Methods.— We used retrograde labeling combined with immunohistochemistry to examine 5‐HT1D receptor immunoreactivity in rat sphenopalatine ganglion neurons that project to the lacrimal gland, nasal mucosa, cerebral vasculature, and trigeminal ganglion. Results.— We found 5‐HT1D receptor immunoreactivity in nerve terminals around postganglionic cell bodies within the sphenopalatine ganglion. All 5‐HT1D‐immunoreactive terminals were also immunoreactive for calcitonin gene‐related peptide but not vesicular acetylcholine transporter, suggesting that they were sensory and not preganglionic parasympathetic fibers. Our retrograde labeling studies showed that approximately 30% of sphenopalatine ganglion neurons innervating the lacrimal gland, 23% innervating the nasal mucosa, and 39% innervating the trigeminal ganglion were in apparent contact with 5‐HT1D receptor containing nerve terminals. Conclusion.— These data suggest that 5‐HT1D receptors within primary afferent neurons that innervate the sphenopalatine ganglion are in a position to modulate the excitability of postganglionic parasympathetic neurons that innervate the lacrimal gland and nasal mucosa, as well as the trigeminal ganglion. This has implications for triptan (5‐HT1D receptor agonist) actions on parasympathetic symptoms in cluster headache.