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.