Expression of messenger molecules and receptors in rat and human sphenopalatine ganglion indicating therapeutic targets

Abstract

BackgroundMigraine and Cluster Headache (CH) are two primary headaches with severe disease burden. The disease expression and the mechanisms involved are poorly known. In some attacks of migraine and in most attacks of CH, there is a release of vasoactive intestinal peptide (VIP) originating from parasympathetic cranial ganglia such as the sphenopalatine ganglion (SPG). Patients suffering from these diseases are often deprived of effective drugs. The aim of the study was to examine the localization of the botulinum toxin receptor element synaptic vesicle glycoprotein 2A (SV-2A) and the vesicular docking protein synaptosomal-associated protein 25 (SNAP25) in human and rat SPG. Additionally the expression of the neurotransmitters pituitary adenylate cyclase activating polypeptide (PACAP-38), nitric oxide synthase (nNOS), VIP and 5-hydroxttryptamine subtype receptors (5-HT1B,1D,1F) were examined.MethodsSPG from adult male rats and from humans, the later removed at autopsy, were prepared for immunohistochemistry using specific antibodies against neurotransmitters, 5-HT1B,1D,1F receptors, and botulinum toxin receptor elements.ResultsWe found that the selected neurotransmitters and 5-HT receptors were expressed in rat and human SPG. In addition, we found SV2-A and SNAP25 expression in both rat and human SPG. We report that all three 5-HT receptors studied occur in neurons and satellite glial cells (SGCs) of the SPG. 5-HT1B receptors were in addition found in the walls of intraganglionic blood vessels.ConclusionsRecent focus on the SPG has emphasized the role of parasympathetic mechanisms in the pathophysiology of mainly CH. The development of next generation’s drugs and treatment of cranial parasympathetic symptoms, mediated through the SPG, can be modulated by treatment with BoNT-A and 5-HT receptor agonists.

Parasympathetic Cholinergic and Neuropeptide Mechanisms of Migraine

“…Another argument testifying the SPG role in pathophysiology of migraine is the enrichment of SPG, besides ACh, with the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP), as one of the main migraine mediators ( 8 , 9 ). Finally, in a recent work ( 10 ) it has been suggested that parasympathetic mechanisms, in particular the neurotransmitters expressed in SPG, are important for induction of cluster headache.…”

Sphenopalatine Ganglion Pulsed Radiofrequency for the Treatment of Refractory Chronic SUNCT and SUNA: A Prospective Case Series

“…Of the 2 radiofrequency modalities normally used in management of headache and facial pain conditions, radiofrequency lesioning can result in permanent or more often temporary hypoesthesia, dysesthesia, or deafferentation pain in the palate, maxilla, or posterior pharynx 14 . Conversely PRF applies a non‐neurodestructive electrical field that has been able to increase early gene expression of c‐Fos immunoreactivity in some neurons without denaturing proteins, suggesting that PRF modulates nervous tissue rather than directly damaging it 18,19 . To avoid potentially permanent side effects and in view of the fact that radiofrequency ablation of the SPG does not seem to be superior to SPG‐PRF in the treatment of CH, 13 the latter modality was used in our patients.…”

The Therapeutic Impact of New Migraine Discoveries

“…The role of PACAP1-38 has been suggested in the ethiopathology of migraine, though some aspects are still yet to be revealed [128][129][130]. PACAP1-38 was detected in the TG [131], in the TNC [132], and also in the parasympathetic otic and sphenopalatine ganglia [133][134]. Elevated levels of PACAP were found in the interictal phase compared to the ictal phase in migraine patients and also in cluster headache attacks [135][136].…”