Activation of the Transcription Factor NF-κB in the Nucleus Trigeminalis Caudalis in an Animal Model of Migraine
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INTRODUCTION
Migraine is a complex disease that involves the mediation of central and peripheral components of the trigeminal pain pathway. Several lines of evidence suggest that pain in migraine is related to the activation of the trigeminovascular system and to the activation of the nucleus trigeminal caudalis (NTC), which conveys the information from the periphery to higher sites.
Infusion of nitroglycerin (NTG) induces spontaneous-like headaches in migraineurs with a delay of hours, but not in control
Animals
Male Sprague–Dawley rats (weight 180–220 g) were divided into groups of four to six animals. All steps were taken at every stage of the experiments to avoid suffering to the animals. The rats were housed in plastic boxes with water and food available ad libitum and kept on a 12-h light:12-h dark cycle.
In the treated groups, animals were injected intraperitoneally with NTG (10 mg/kg b.w.) and perfused transcardially 4 h later (previously identified as the time of maximal Fos expression) with saline
RESULTS
Data regarding Fos expression following the administration of NTG confirmed our previous studies: NTG induced a significant activation of neurons located in lamina I and II of NTC (Fig. 1). The number of p65-immunoreactive neurons in this nucleus was significantly higher in the group treated with NTG when compared with the control group (Fig. 2). The highest concentration of p65-positive nuclei was observed in lamina I, and to a lesser extent in lamina II. Western blotting analysis confirmed
DISCUSSION
In the neuroscience and neurological fields, a general agreement exists on the trigeminovascular mediation of migraine attacks. Actually trigeminovascular-mediated neurogenic inflammation in perivascular tissues within the dura mater has been widely accepted as the “efferent arm” of the process (Moskowitz, 1992). NO and cytokines may contribute to inflammation and sensitization of primary afferents of the trigeminovascular system (Opree and Kress, 2000) and some authors have suggested that the
ACKNOWLEDGMENT
This study was supported by a grant of the Ministry of Health (RC 2002-2004) and by EU Eurohead, LSHM-CT-2004-504837.
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2020, Neurobiology of DiseaseCitation Excerpt :The data gathered in this study do not warrant definite conclusions regarding the precise mechanisms that are engaged selectively by the pre-NTG dosing of URB597. One interesting hypothesis is that the simultaneous elevations of both AEA and PEA may be required to prevent the activation of the inflammatory pathway triggered by NTG (Greco et al., 2005). Further experimental data are needed to confirm this speculation.
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2019, Progress in NeurobiologyCitation Excerpt :The increased release of artemin from the dural vasculature may play a role in the sensitization of dural afferents (McIlvried et al., 2010) and contribute to meningeal inflammation (Malin et al., 2006; Shang et al., 2016). Systemic NTG administration activates inflammatory pathways (Greco et al., 2005, 2015b; Greco et al., 2016), probably as a consequence of the increased availability of NO in trigeminovascular terminals. NTG injection indeed induced an up-regulation of pro-inflammatory genes, with a subsequent delayed inflammatory reaction in the dura mater and central areas of the rat (Reuter et al., 2002; Kim et al., 2008; Greco et al., 2016).