Role of neuropeptides in migraine: where do they stand in the latest expert recommendations in migraine treatment?

Abstract

Many factors have been implicated in the pathogenesis of migraine headache, including activation of the trigeminovascular system, dysfunction of: cerebral blood vessels, circulating vasoactive substances, mitochondrial energy metabolism, brain oxygenation and metabolism, platelet disorder, alterations in serotonin levels, low levels of brain tissue magnesium, altered transport of ions across the cell membrane, and inheritance and dysfunction of the brainstem periaqueductal gray matter. The headache phase of migraine is associated with cerebral vasodilation and inflammation, presumably mediated by the release of vasoactive substances and neuropeptides including CGRP (calcitonin gene-related peptide). Increased serum CGRP levels have been detected during migraine and cluster headache. One strategy to treat migraine is to inhibit the release of neuropeptides or to block their receptors. This article briefly reviews some experimental and clinical investigations focused on neuropeptide involvement in migraine. Drug Dev Res 68: 294-314, 2007.

Dysregulation of Multiple Signaling Neurodevelopmental Pathways during Embryogenesis: A Possible Cause of Autism Spectrum Disorder

“…It functions during the stimulation of brainstem reflexes and is found to lower blood velocity in the middle portion of the cerebral artery. Both the PACAP and VIP are involved in the homeostatic mechanism of the immune system and thought to have an anti-inflammatory effect on the adaptive and innate immune responses, thereby promoting Th2 action and suppressing pro-inflammatory Th1 responses [ 92 , 93 ]. The Neurotrophic agent BDNF of the nerve growth family, along with other neurotrophins, acts on tyrosine kinase receptors with greater affinity and acts on the low-affinity p75 receptor.…”

“…In sensory neurons, the CGRP is a neurotransmitter and neuromodulator that coexists with substance P, neurokinin A (NKA), and glutamate as an endogenous vasodilator peptide [ 96 ]. The CGRP increases the release of the BDNF from trigeminal ganglia, suggesting that the BDNF might be an endogenous mediator of nociception plasticity [ 93 ]. Brondino et al [ 97 ] suggested that it may also be part of a biochemical continuum that essentially focuses on autistic characters in the general population.…”