| BackgroundMigraine, a common recurrent neurovascular disorder, is characterized by unilateral and throbbing headaches accompanied by photophobia, phonophobia, nausea, and vomiting. It has been discovered that the trigeminovascular system plays a key role in migraine headache pathophysiology. Several lines of evidence suggest that pain in migraine is related to the activation of both the perivascular trigeminal sensory nerve fibers and the trigeminal nucleus caudalis, which transmits the signal from the periphery to higher sites. Of note, neuropeptide release(e.g., calcitonin gene-related peptide and Substance P) and the expression of c-fos like immunoreactivity (c-fos LI) within trigeminal nucleus caudalis neurons are activation markers of thetrigeminal nerve system.CGRP has also been reported to co-exist with SP in trigeminal ganglion nerve cells and their processes, which densely innervate the cerebral blood vessels. Direct chemical, thermal, or electrical stimulation of trigeminal sensory nerves in rodents induces vascular permeability changes that are mediated predominantly by the tachykinins (e.g., SP and NKA) and vasodilatation (i.e., the axon reflex flare) that is mediated predominantly by CGRP. Furthermore, it is well established that plasma CGRP levels are increased during a migraine attack. Migraine patients that are infused with CGRP develop a delayed headache, fulfilling the criteria of a migraine. Moreover, there are reports that treatment of a migraine attack with sumatriptan reduces the elevated CGRP levels. In addition, the immediate early gene c-fos is one of the most studied genes in the central nerve system as a marker for neuronal activation. The activation of the trigeminal nucleus caudalis often has been revealed by means of expression of the immediate early gene protein c-fos. In experimental animals bolus administration of nitroglycerin (10mg/kg i.p.) led to c-fos expression within the trigeminal nucleus caudalis. Moreover, sustained c-fos expression in the trigeminal nucleus caudalis is sufficient to highlight the activation of central trigeminal pathways.ObjectivesRecently, we found that the ligation of middle meningeal artery and superficial temporal artery and severance of greater superficial petrosal nerve was effective for the treatment of intractable cases of migraine, suggesting the involvement of middle meningeal artery in migraine pathophysiology. Herein, our study investigated the effects of heating coagulation of middle meningeal artery on plasma CGRP and SP level and c-fos gene expression in trigeminal nucleus caudalis in migraine rat model triggered by nitroglycerin to explore the efficacy mechanism of heating coagulation of middle meningeal artery in the treatment of intractable cases of migraine. According this we can provide a theoretical and experimental basis for evaluating the surgery for the treatment of intractable cases of migraine.MethodsForty-eight female Wistar rats were randomly divided into four groups, with six subjects in each group. In isotonic saline group (group A), rats were treated with isotonic saline, In nitroglycerin group (group B), rats were injected subcutaneously with 10mg/kg nitroglycerin to set up the animal model of migraine, In sham operation group (group C), rats were merely exposed middle meningeal artery and then injected with nitroglycerin (10 mg/kg). In operation group (group D), rats were firstly subjected to heat coagulation of middle meningeal artery and, subsequently, injected with nitroglycerin (10mg/kg). Following the injection, the animal's behavior was continuously recorded by an observer, and each group was subdivided into another two equal groups after constructing successfully animal model. The mRNA and protein expression of c-fos gene in trigeminal nucleus caudalis were detected by RT-PCR and the Western blot respectively. Radioimmunoassay was employed to measure the contents of CGRP and SP in venous plasma.ResultsInjection of 10 mg/kg nitroglycerin was able to trigger the animal model of migraine as evidenced by the appearances of a series of symptoms, such as, scratching head frequently, climbing cage and ear red. Rats in group A occasionally showed off scratching head, whereas, rats from group B and group C presented with much severe symptoms. Of note, rats in group D appeared slightly scratching head and climbing page, without ear red compared with group B and C. At the same time, the contents of plasma CGRP for each group were respectively (12.14±4.99)pg/ml, (57.34±10.27) pg/ml, (51.40±13.13)pg/ml and (27.96±8.32)pg/ml, the contents of SP were respectively (6.78±2.09)pg/ml, (20.03±5.74)pg/ml, (22.33±6.83)pg/ml and (13.27±2.31)pg/ml. That is, the levels of plasma CGRP and SP and the c-fos gene relative expression in group B, group C, or group D was increased significantly compared with that of group A(P<0.05). Furthermore, the plasma CGRP and SP levels and the c-fos gene relative expression in group D were much lower than that in group B and group C (P<0.05), but there was no statistical difference between group B and group C (P>0.05).ConclusionsOur study suggested that heat coagulation of middle meningeal artery may attenuate head complaint of rat induced by nitroglycerin, and it concluded that the middle meningeal artery plays a primary role in the pathophysiology of rat migraine model triggered by nitroglycerin and the efficacy may play a part in containing the release of CGRP and SP and decreasing c-fos expression and containing activation of neurons in trigeminal nucleus caudalis.
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