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Experimental models for the study of migraine - State of the art and future developments
The possibility to investigate the mechanisms underlying migraine attacks in reliable animal models has yielded a considerable amount of data during recent years. The interpretation, if not the understanding of the very early events that are able to trigger the cascade of events that periodically constrain a considerable number of people in miserable conditions, has allowed the identification of the anatomical structures which are involved in the process and, at least partly, the mechanisms through which these structures are activated or act. The various animal models used by the different research groups are concisely presented along with the results that the researchers have collected
The Grand Challenge in Cranial Pain—From Migraine to Cranial Neuralgias: Understanding Differences and Similarities to Advance Knowledge and Management
Systemic nitroglycerin activates peptidergic and catecholaminergic pathways in rat brain.
In this study, we carried out an immunohistochemical evaluation of the neurochemical characteristics of neurons that are activated (i.e., express Fos protein) in response to systemic administration of nitroglycerin. In the brain stem, a significant percentage of activated neurons contained noradrenaline as a neurotransmitter, whereas only a few of them contained serotonin. In the paraventricular and supraoptic nuclei of the hypothalamus, numerous Fos-immunoreactive neurons were also positive for vasopressin, oxytocin, and corticotropin-releasing factor. Codistribution with corticotropin-releasing factor was also observed in the central nucleus of the amygdala. Our findings point out a prominent role for catecholaminergic and peptidergic pathways in the brain in response to systemic nitroglycerin
NADPH-diaphorase activity and Fos expression in brain nuclei following nitroglycerin administration.
Organic nitrates are considered nitric oxide donors in that they have been shown to form nitric oxide in vitro and in vivo. Nitroglycerin is an organic nitrate which possesses peculiar activities mediated, to some extent, by the central nervous system via the noradrenergic system. Previous reports have shown that systemic nitroglycerin is able to induce Fos expression in brain nuclei which are known to contain nitric oxide synthesizing enzyme. Neuronal NADPH-diaphorase has been shown to be a nitric oxide synthase. Thus, in this study we used NADPH-diaphorase histochemistry to evaluate the distribution of Fos-immunoreactive cells within neurons which contain nitric oxide synthase. The data showed co-localization of Fos with NADPH-diaphorase activity in numerous neurons of the paraventricular and supraoptic nuclei of the hypothalamus. In the brainstem, a few neurons were doubly labeled for Fos and NADPH-diaphorase activity, but NADPH-diaphorase positive fibers and Fos-immunoreactive neurons were consistently co-distributed in the locus coeruleus, parabrachial nucleus, nucleus tractus solitarius and spinal trigeminal nucleus caudalis. These findings demonstrate that nitroglycerin administration activates a selective group of neurons which are a source of nitric oxide or which are in close proximity with neuronal processes containing nitric oxide synthase, and suggest that the nitric oxide synthase synthesizing pathway may be involved at various levels in the central effect of nitroglycerin
Systemic nitroglycerin induces Fos immunoreactivity in brainstem and forebrain structures of the rat.
Nitroglycerin is a vasodilator which induces vascular relaxation by releasing nitric oxide in the wall of blood vessels. It has been suggested that the cardiovascular inhibitory responses which are induced by this drug are mediated by central structures. In this study, we evaluated the distribution and intensity of Fos immunoreactivity in rat brain nuclei following the systemic administration of nitroglycerin. In the medulla, a significant number of Fos-immunoreactive neurons were observed in the nucleus tractus solitarius, ventrolateral medulla, area postrema and spinal trigeminal nucleus caudalis. A robust staining was seen in the parabrachial nucleus, locus coeruleus and ventrolateral periaqueductal grey. In the hypothalamus, Fos-positive cells were densely packed in the paraventricular and supraoptic nuclei. Other areas where significant staining was observed include the central nucleus of the amygdala and the subfornical organ. These findings demonstrate that the systemic administration of nitroglycerin is capable of activating a spectrum of functionally diverse brain regions. This spectrum includes areas involved in reflex adjustments to nitroglycerin-induced hypotension, areas involved in sensory nociceptive perception and areas associated with integrative regulation of autonomic, behavioral and neuroendocrine functions
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