Calcitonin Gene-Related Peptide and Adrenomedullin Levels During Ictal and Interictal Periods in Patients With Migraine

Abstract

BackgroundPeptides related to calcitonin gene-related peptide (CGRP) have been suggested to have a role in migraine. Adrenomedullin (AM) might be a candidate molecule because it is related to pain pathways in the peripheral and central nervous systems and uses the same receptors as CGRP. MethodologyIn this study, we examined the serum CGRP and AM levels during unprovoked ictal and interictal periods of 30 migraine patients as well as 25 healthy controls. Another focus of this study was on the association of CGRP and AM levels with clinical features. ResultsMean serum AM levels were 15.80 pg/mL (11.91-21.43 pg/mL) in the ictal and 15.85 pg/mL (12.25-19.29 pg/mL) in the interictal periods in the migraine group and 13.36 pg/mL (10.84-17.18 pg/mL) in the control group. Mean serum CGRP levels were 2.93 pg/mL (2.45-3.90 pg/mL) in the ictal and 3.25 pg/mL (2.85-4.67 pg/mL) in the interictal periods in the migraine group and 3.03 pg/mL (2.48-3.80 pg/mL) in the control group. There were no statistical differences between ictal and/or interictal AM and CGRP levels (p = 0.558 and p = 0.054, respectively) which were also comparable with the results of the control group (p = 0.230, p = 0.295, p = 0.987, p = 0.139, respectively). Ictal serum CGRP and/or AM levels did not correlate with any of the reported clinical features. ConclusionsSerum AM and CGRP levels are similar in interictal and unprovoked ictal periods in migraine patients and as well in controls. These results do not indicate that these molecules do not have a role in migraine pathophysiology. Considering the broad mechanisms of action of peptides in the CGRP family, further studies are needed in larger cohorts.

Untangling the mess of CGRP levels as a migraine biomarker: an in-depth literature review and analysis of our experimental experience

“…The kit from Biorbyt showed an elevated content of CGRP (range: 150-980pg/mL) compared to what has been reported in the bibliography [ 24 – 27 , 29 , 38 , 49 , 54 ] when undiluted serum samples were used. Moreover, the reproducibility of the kit was not satisfactory as the assayed samples did not meet the intra and inter-assay coefficient of variance criteria set by the manufacturer (> 10% and > 12%, respectively).…”

“…Therefore, these methodologies, sampling differences and variable data displays did not allow for a meta-analysis, and the absolute CGRP range among all the studies could be inferred, showing a wide range of concentrations (2.45–219,700 pg/mL) [ 28 , 54 ].…”

“…Several studies have reported elevation of the peptide in ictal and/or interictal phases in medication-free periods of migraine patients [ 14 – 38 ], the reduction of the CGRP levels after abortive and prophylactic treatment [ 26 , 28 , 38 – 44 ] and the induction of migraine-like headaches when infused in humans [ 45 ]. Despite these results, there are other works contradicting the findings [ 35 , 46 – 54 ] and which emphasize the way until its eventual validation and clinical use is still far way to become a reality. The source of such discrepancies, although still unknown, is most probably multifactorial.…”