Calcitonin gene-related peptide (CGRP): a new target for migraine

Annu Rev Pharmacol Toxicol. 2015;55:533-52. doi: 10.1146/annurev-pharmtox-010814-124701. Epub 2014 Oct 8.

Abstract

Migraine is a neurological disorder that manifests as a debilitating headache associated with altered sensory perception. The neuropeptide calcitonin gene-related peptide (CGRP) is now firmly established as a key player in migraine. Clinical trials carried out during the past decade have proved that CGRP receptor antagonists are effective for treating migraine, and antibodies to the receptor and CGRP are currently under investigation. Despite this progress in the clinical arena, the mechanisms by which CGRP triggers migraine remain uncertain. This review discusses mechanisms whereby CGRP enhances sensitivity to sensory input at multiple levels in both the periphery and central nervous system. Future studies on epistatic and epigenetic regulators of CGRP actions are expected to shed further light on CGRP actions in migraine. In conclusion, targeting CGRP represents an approachable therapeutic strategy for migraine.

Keywords: neuromodulation; neuropeptide; photophobia; sensitization; trigeminovasculature.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Analgesics / therapeutic use*
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Calcitonin Gene-Related Peptide / antagonists & inhibitors*
  • Calcitonin Gene-Related Peptide / genetics
  • Calcitonin Gene-Related Peptide / immunology
  • Calcitonin Gene-Related Peptide / metabolism
  • Calcitonin Gene-Related Peptide Receptor Antagonists*
  • Drug Design*
  • Epigenesis, Genetic / drug effects
  • Epistasis, Genetic / drug effects
  • Humans
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / genetics
  • Migraine Disorders / metabolism
  • Migraine Disorders / physiopathology
  • Molecular Targeted Therapy / methods*
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Pain Perception / drug effects
  • Pain Threshold / drug effects
  • Receptors, Calcitonin Gene-Related Peptide / genetics
  • Receptors, Calcitonin Gene-Related Peptide / immunology
  • Receptors, Calcitonin Gene-Related Peptide / metabolism
  • Signal Transduction / drug effects

Substances

  • Analgesics
  • Antibodies, Monoclonal
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Receptors, Calcitonin Gene-Related Peptide
  • Calcitonin Gene-Related Peptide