Systemic nitroglycerin increases nNOS levels in rat trigeminal nucleus caudalis

Abstract

Systemic administration of nitroglycerin, a nitric oxide donor, triggers in migraineurs a delayed attack of unknown mechanisms. Subcutaneous nitroglycerin (10 mg/kg) produced a significant increase of nitric oxide synthase (NOS)- and c-fos-immunoreactive neurons in the cervical part of trigeminal nucleus caudalis in rats after 4 h. This effect was not observed in the thoracic dorsal horn. Similar increase of NOS and c-fos was obtained in the brain stem after a somatic nociceptive stimulus, i.e. on the side of the formalin injection in the lip. Nitric oxide is thus able to increase NOS availability in second order nociceptive trigeminal neurons, which may be relevant for central sensitization and the understanding of its effect in migraine.

Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect

“…It is also well-known, that NTG-a nitric oxide donor (NO)-can initiate trigeminal activation and sensitization in animals as well (Pardutz et al, 2000;Tassorelli and Joseph, 1995). In rats, it has been shown that NTG produced an increase in the area covered by 5-HT-immunoreactive fibres (Pardutz et al, 2002), which suggests that NO influences the 5-HT system.…”

Role of pituitary adenylate cyclase-activating polypeptide (pacap) in the trigeminovascular system: preclinical and clinical results

“…c-fos, CGRP [98,136], nNOS-immunoreactivity in the NTG model [89], and c-fos [137], nNOS [111], CGRP alterations [110] following the ES of the TRG.…”

“…It is abundant in the superficial layers of the dorsal horn of the spinal cord [89][90][91]. The inhibition of NOS was showed to be able to ameliorate the symptoms of spontaneous migraine attacks [92].…”

“…The delay in the action of NO triggers a typical attack in migraineurs, which is possibly related to the activation of trigeminal Aδ and C fibres leading to central sensitization at the level of TNC [89].…”

Modulatory effect of synthetic kynurenic acid derivatives on the nitroglycerin-induced trigeminal activation and sensitization in rats

“…Increase in neuronal NOS-(nNOS) and CaMKIIα-IR neurones in the C1-C2 were detected four hours after systemic administration of NTG in male rats, suggesting the presence of selfamplifying mechanisms in this area, possibly linked to a central sensitization process (Pardutz et al, 2000;. The changes observed in expression of sensitization markers were attenuated by lysine acetylsalicylate and by NS398 (selective cyclooxygenase-2 inhibitor) (Pardutz et al, 2004;Varga et al, 2007;.…”