Vasoactive Intestinal peptide modulates c-Fos activity in the trigeminal nucleus and dura mater mast cells in sympathectomized rats

Abstract

Neurogenic inflammation in the dura mater caused by trigeminal nociceptive activation has been implicated in the pathophysiology of migraine. Vasoactive intestinal polypeptide (VIP) is a powerful neuroprotective neuropeptide that can modulate mast cell behavior. Migraine is also associated with sympathetic insufficiency. This study investigates the effects of VIP on the number of mast cells in the dura mater and on c-Fos expression in the trigeminal nucleus of sympathectomized rats. Experiments were carried out with 32 Sprague-Dawley male rats with body weights of 200-250 g. In the sympathectomized group, the left superior cervical sympathetic ganglion was removed. In the sympathectomized + VIP group, postoperative VIP 25 ng/kg/day (0.2 ml) was administered for 5 days. In the sham group, the ganglion and nerves were exposed but not dissected. Dura maters were stained with toluidine blue, and brainstems were labeled by indirect immunohistochemistry for c-Fos. Sympathectomy significantly increased the number of mast cells in both the ipsilateral and the contralateral dura mater (P < 0.001). VIP decreased the number of mast cells in both sides of the dura mater in sympathectomized rats. VIP also decreased c-Fos expression in the ipsilateral trigeminal nucleus of sympathectomized rats (P < 0.001). In the context of an experimental superior cervical ganglionectomy model of migraine, VIP is an efficient modulator of neurogenic inflammation of the dura.

Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats

“…The increase in the plasma levels of CGRP is a biomarker for trigeminovascular activation during migraine attacks and cluster headaches . In addition, to examine migraine, proto‐oncogene c‐fos expression has also been widely used as a marker for neuronal activation in brainstem . In the present study, in vivo application of GTN significantly induced an increase in the CGRP levels both in plasma and the trigeminal ganglion neurons.…”

“…The release of these neuropeptides following the activation of the trigeminal ganglion was shown to be responsible for the neurogenic inflammation. This is the phenomenon that underlies the pathophysiology of migraine . The increase in the plasma levels of CGRP is a biomarker for trigeminovascular activation during migraine attacks and cluster headaches .…”

“…Whole‐mount dural preparations were prepared onto glass slides with polylysine as previously described by Kilinc et al To observe mast cells in the dura mater, the preparations were stained with toluidine blue (pH 2.5). Dural mast cells were counted in five objective areas containing the main branches of the middle meningeal artery in both left and right sides of each dura mater and classified as either degranulated or non‐degranulated with a light microscope (CX21 Olympus, Tokyo, Japan) by a blinded observer.…”

“…This is the phenomenon that underlies the pathophysiology of migraine. 1,27,28 The increase in the plasma levels of CGRP is a biomarker for trigeminovascular activation during migraine attacks and cluster headaches. 2,7,8 In addition, to examine migraine, protooncogene c-fos expression has also been widely used as a marker for neuronal activation in brainstem.…”

Abstracts and Citations

“…An increase in cerebral blood flow upon stimulation of pre‐ or postganglionic fibers of the sphenopalatine ganglion has been demonstrated in some animals, and can be mimicked by local administration of ACh and VIP in vivo. This paper, and the paper from Kilinc et al below, extend the available data on the possible influences of the parasympathetic system on cerebrovascular control and provide some link to brainstem circuitry and GABA. I have added a recent reference from Stroke on the relative contributions from various sources to autoregulation of the cerebrovasculature.…”