Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine

Neurology. 2013 Oct 1;81(14):1191-6. doi: 10.1212/WNL.0b013e3182a6cb72. Epub 2013 Aug 23.


Objective: To determine calcitonin gene-related peptide (CGRP) levels outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine (CM).

Methods: Women older than 17 years and diagnosed with CM were recruited. Matched healthy women with no headache history and women with episodic migraine (EM) served as control groups, together with a series of patients with episodic cluster headache in a pain-free period. CGRP levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack and having taken no symptomatic medication the day before. For ethical reasons, preventatives were not stopped.

Results: We assessed plasma samples from 103 women with CM, 31 matched healthy women, 43 matched women with EM, and 14 patients with episodic cluster headache matched for age. CGRP levels were significantly increased in CM (74.90 pg/mL) as compared with control healthy women (33.74 pg/mL), women with EM (46.37 pg/mL), and patients with episodic cluster headache (45.87 pg/mL). Thresholds of 43.45 and 58.22 pg/mL optimize the sensitivity and specificity to differentiate CM from healthy controls and EM, respectively. In the CM group, CGRP levels were significantly increased in women with a history of migraine with aura vs those only experiencing migraine without aura. Variables such as age, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption, or kind of preventative treatment did not significantly influence CGRP levels.

Conclusion: Increased CGRP level measured in peripheral blood outside migraine attacks and in the absence of symptomatic medication could be a biomarker helping in the diagnosis of CM.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Calcitonin Gene-Related Peptide / biosynthesis*
  • Calcitonin Gene-Related Peptide / blood
  • Chronic Disease
  • Cluster Headache / blood
  • Cluster Headache / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / blood*
  • Migraine Disorders / classification
  • Migraine Disorders / genetics
  • Migraine with Aura / blood
  • Migraine with Aura / genetics
  • Migraine without Aura / blood
  • Migraine without Aura / genetics
  • Up-Regulation / physiology*
  • Young Adult


  • Biomarkers
  • Calcitonin Gene-Related Peptide