CGRP as a neuropeptide in migraine: lessons from mice - PubMed (original) (raw)

Review

CGRP as a neuropeptide in migraine: lessons from mice

Andrew F Russo. Br J Clin Pharmacol. 2015 Sep.

Abstract

Migraine is a neurological disorder that is far more than just a bad headache. A hallmark of migraine is altered sensory perception. A likely contributor to this altered perception is the neuropeptide calcitonin gene-related peptide (CGRP). Over the past decade, CGRP has become firmly established as a key player in migraine. Although the mechanisms and sites of action by which CGRP might trigger migraine remain speculative, recent advances with mouse models provide some hints. This brief review focuses on how CGRP might act as both a central and peripheral neuromodulator to contribute to the migraine-like symptom of light aversive behaviour in mice.

Keywords: CGRP; calcitonin gene-related peptide; migraine; mouse model; neuropeptide; photophobia.

© 2015 The British Pharmacological Society.

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Figures

Figure 1

Figure 1

Calcitonin gene-related peptide (CGRP)-induced light-aversive behaviour in nestin/human receptor activity-modifying protein 1 (hRAMP1) mice. (A) A schematic of the CGRP receptor complex consisting of calcitonin-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and receptor component protein (RCP) is shown (reproduced from Russo [8]). (B) The conditional hRAMP1 expression strategy is outlined (modified from Zhang et al. [60]). The parental green fluorescent protein (GFP)–hRAMP1 mouse transgene contains a GFP stop sequence that prevents the expression of hRAMP1 in the absence of Cre recombinase action at loxP sites. After crossing GFP–hRAMP1 mice with nestin–cre mice, the GFP stop sequence is removed and hRAMP1 is expressed in the nervous system of double transgenic nestin/hRAMP1 mice. (C) CGRP administration by intracerebroventricular injection caused nestin/hRAMP1 mice to spend less time in the light compared with control mice or mice injected with vehicle. *P < 0.05). Data obtained from Recober et al. [34]

Figure 2

Figure 2

Potential sites of CGRP action in light-aversive behaviour. The rodent brain is shown schematically, with arrows indicating pathways between relevant nuclei and input from the trigeminovascular system and light detected by the eye. These nuclei have calcitonin gene-related peptide (CGRP) receptors and respond to CGRP to modulate either affective behaviour or spinal trigeminal nucleus activity. Not all pathways are shown in this simplified presentation. Abbreviations are as follows: Amg, amygdala; Hyp, hypothalamus (which refers to the A11 nucleus and paraventricular nucleus); TG, trigeminal ganglion (which includes neurones and satellite glia); PAG, periaqueductal gray; Po, posterior thalamic nuclei (which include the posterior, ventroposteromedial and lateral posterior thalamus); Rmg, raphe magnus nucleus; SpV, spinal trigeminal nucleus; S1, S2, somatosensory cortex; V1, V2, visual cortex. Dural mast cells and blood vessels with associated trigeminal fibres and Schwann cells (not shown) are also indicated (brown line represents the dura)

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