Sensory Neuropeptides (Substance P, Calcitonin Gene-Related Peptide) and Vasoactive Intestinal Polypeptide in Human Saliva: Their Pattern in Migraine and Cluster Headache

Abstract

Substance P, calcitonin gene-related peptide and vasoactive intestinal polypeptide-like immunoreactivities have been evaluated in the saliva of 15 subjects suffering from migraine without aura and 16 control subjects. All three peptides were also measured in the symptomatic/non-symptomatic side saliva sampled from 10 cluster headache sufferers during the cluster period, 5 cluster headache sufferers out of the cluster period, as well as in the right and left side saliva of 18 control subjects. The most interesting result gives a clear difference in common migraine and cluster headache salivary vasoactive intestinal polypeptide-like immunoreactivity contents. In fact, these are enhanced during cluster headache attack and decreased during migraine attack when compared with the interictal period vasoactive intestinal polypeptide-like immunoreactivity levels. Another remarkable finding concerns the significant increase of substance P-like immunoreactivity and calcitonin gene-related peptide-like immunoreactivity levels, from basal values, in the saliva sampled during both migraine and cluster headache attacks. Control subjects showed a calcitonin gene-related peptide-like immunoreactivity and substance P-like immunoreactivity salivary contents significantly higher than migraine sufferers' saliva sampled in basal conditions. Conversely, calcitonin gene-related peptide-like immunoreactivities levels in controls were lower than in cluster headache sufferers' saliva obtained during intervals. Finally, during cluster headache attacks the enhancement of substance P-like immunoreactivity and vasoactive intestinal polypeptide-like immunoreactivity salivary contents interest the non-symptomatic side, whereas the symptomatic side salivary substance P-like immunoreactivity and vasoactive intestinal polypeptide-like immunoreactivity contents remain unchanged. These findings do not allow any final conclusion. However, this biochemical evaluation indicates relevant changes of the salivary neuropeptides in diseases, such as migraine and cluster headache, in which pain transmission is surely involved.

Migraine and neuropeptides

“…electrical stimulation of the superior sagittal sinus, results in elevations of CGRP and VIP, but not NPY and SP (Zagami et al, 1990). No elevation of SP in the cranial venous outflow was detected during spontaneous migraine attacks Goadsby et al, 1990), whereas the salivary SP immunoreactivity was increased during spontaneous migraine attacks without aura versus the level in control subjects (Nicolodi and Del Bianco, 1990). In chronic migraine patients, the plasma and saliva levels of SP were higher than those in control subjects, and associated with pain intensity (Jang et al, 2011).…”

Quantitative analysis of substance P, neurokinin A and calcitonin gene‐related peptide in gingival crevicular fluid associated with painful human teeth

“…The rationale is that the composition of these fluids may be changed by virtue of their proximity to an inflammatory focus. In this context, the levels of neuropeptides, particularly SP and CGRP have been measured in human saliva from patients with migraine and cluster headache (7). In general, nerves containing SP, NKA, and CGRP mediate nociception, modulate blood flow, and control certain aspects of tissue reaction to injury (8, 9).…”

Role of neuropeptides in migraine: where do they stand in the latest expert recommendations in migraine treatment?

“…A significant increase in NKA and CGRP levels has been detected during headache attacks in young migraine sufferers [Gallai et al, 1985]. SP and CGRP levels have also been reported to increase in the salivary secretions of migraine and cluster headache patients [Nikolodi and Del Bianco, 1990]. However, except for a recent investigation [Fusayasu et al, 2007], most other reports show that there is a lack of SP in the blood of human subjects during migraine headache [Goadsby et al, 1990;Friberg et al, 1994].…”