Neuropeptide y inhibits the trigeminovascular pathway through NPY Y1 receptor: Implications for migraine

Margarida Martins Oliveira, Simon Akerman, Isaura Tavares, Peter J. Goadsby*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)
159 Downloads (Pure)


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 -1), and investigated the receptors involved by studying NPY Y 1 (30 μg·kg -1), Y 2 (30 μg·kg -1), and Y 5 receptor agonists (100·μg·kg -1), and NPY Y 1 receptor antagonist (30 μg·kg -1). NPY (30 and 100 μg·kg -1) significantly reduced TCC neuronal firing in response to dural-evoked trigeminovascular activation, but only NPY (30 μg·kg -1) significantly reduced spontaneous trigeminal firing. NPY Y 1 receptor agonist also significantly reduced dural-evoked and spontaneous TCC neuronal firing. NPY (10 μg·kg -1), NPY Y 2, and Y 5 receptor agonists, and the NPY Y 1 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 Y 1 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.

Original languageEnglish
Pages (from-to)1666-1673
Number of pages8
Issue number8
Publication statusPublished - 8 Jun 2016


  • Appetite
  • Headache
  • Migraine
  • Neuropeptide Y
  • Trigeminovascular


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