Abstract
Migraine is a painful neurologic disorder with premonitory symptomatology that can include disturbed appetite. Migraine pathophysiology involves abnormal activation of trigeminocervical complex (TCC) neurons. Neuropeptide Y (NPY) is synthesized in the brain and is involved in pain modulation. NPY receptors are present in trigeminal ganglia and trigeminal nucleus caudalis suggesting a role in migraine pathophysiology. The present study aimed to determine the effect of systemic administration of NPY on TCC neuronal activity in response to dural nociceptive trigeminovascular activation. We performed in vivo electrophysiology in anesthetized rats, administered NPY (10, 30, and 100 µg·kg), and investigated the receptors involved by studying NPY Y1 (30 µg·kg), Y2 (30 µg·kg), and Y5 receptor agonists (100·µg·kg), and NPY Y1 receptor antagonist (30 µg·kg). NPY (30 and 100 µg·kg) significantly reduced TCC neuronal firing in response to dural-evoked trigeminovascular activation, but only NPY (30 µg·kg) significantly reduced spontaneous trigeminal firing. NPY Y1 receptor agonist also significantly reduced dural-evoked and spontaneous TCC neuronal firing. NPY (10 µg·kg), NPY Y2, and Y5 receptor agonists, and the NPY Y1 receptor antagonist had no significant effects on nociceptive dural-evoked neuronal firing in the TCC or spontaneous trigeminal firing. This study demonstrates that NPY dose dependently inhibits dural-evoked trigeminal activity, through NPY Y1 receptor activation, indicating antinociceptive actions of NPY in a migraine animal model. Based on the role of NPY in appetite regulation, it is possible that disruption of the NPY system might explain changes of appetite in migraineurs.
Highlights
Migraine is considered a complex brain disorder[3,22] and is the sixth most common cause of disability in the world.[19]
We explored neuropeptide Y (NPY) Y1, Y2, and Y5 receptor pharmacology in this animal model because mRNA encoding human NPY Y1 and NPY Y2 receptors is detected in the cerebral and meningeal arteries and in human trigeminal ganglia[47]; NPY Y1, Y2, and Y5 receptors are present in rodent trigeminal nucleus,[40] and these receptors have a major role in hypothalamic appetite control.[53]
Most neurons were located in lamina V of the dorsal horn at the level of the cervicomedullary junction, at an average depth of 476 6 27 mm, and the electrode placement was confirmed in all animals by an electrothermolytic lesion in the trigeminocervical complex (TCC) (Fig. 1C, D)
Summary
Migraine is considered a complex brain disorder[3,22] and is the sixth most common cause of disability in the world.[19] Neuroimaging studies in the premonitory phase, which represents the earliest clinical manifestations of the migraine attack,[23] have demonstrated hypothalamic activation,[32] while a somewhat different hypothalamic site is activated during the attack.[13] This is in agreement with earlier animal studies,[6,7,11,31] establishing the hypothalamus as an important brain area in migraine pathophysiology Disturbed appetite, such as thirst, hunger, or food craving, or feeding schedules have been reported anecdotally as triggers,[9] or as Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Oliveira et al 157 (2016) 1666–1673 symptoms in the premonitory phase of the migraine attack.[14,18,43] Importantly, these premonitory symptoms are regulated in part by the hypothalamus that in turn implicates appetite-related neuropeptides, including neuropeptide Y (NPY)
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