Effects of endurance exercise on serum concentration of calcitonin gene-related peptide (CGRP): a potential link between exercise intensity and headache

Cantor Tarperi 1 , Fabian Sanchis-Gomar 2 , Martina Montagnana 3 , Elisa Danese 3 , Gian Luca Salvagno 3 , Matteo Gelati 3 , Kristina Skroce 1 , Federico Schena 1 , and Giuseppe Lippi 3
  • 1 School of Sport and Exercise Sciences, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
  • 2 Department of Physiology, Faculty of Medicine, University of Valencia and INCLIVA Biomedical Research Institute, Av. Blasco Ibañez, 15, 46010 Valencia, Spain
  • 3 Section of Clinical Biochemistry, University of Verona, Verona, Italy
Cantor Tarperi
  • School of Sport and Exercise Sciences, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
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, Fabian Sanchis-Gomar
  • Corresponding author
  • Department of Physiology, Faculty of Medicine, University of Valencia and INCLIVA Biomedical Research Institute, Av. Blasco Ibañez, 15, 46010 Valencia, Spain
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, Martina Montagnana, Elisa Danese, Gian Luca Salvagno, Matteo Gelati, Kristina Skroce
  • School of Sport and Exercise Sciences, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
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, Federico Schena
  • School of Sport and Exercise Sciences, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
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and Giuseppe Lippi

Abstract

Background

Calcitonin gene-related peptide (CGRP) is a powerful neuropeptide that is strongly involved in headache pain pathogenesis by triggering vasodilation, mast cell degranulation and neurogenic inflammation. This evidence has prompted us to investigate the acute influence of endurance exercise on CGRP concentration in blood.

Methods

The study population consisted of 48 male amateur runners, who ran a half-marathon distance at 75%–85% of maximal oxygen uptake. Blood was drawn before the run (pre-run) and immediately after each runner ended his trial (post-run). The serum concentration of CGRP was measured with a commercial enzyme-linked immunosorbent assay (ELISA) technique.

Results

Overall, 22/48 subjects (45.8%) reported suffering from headache, three of whom (6.2%) had an exertional headache, whilst 26/48 (54.2%) subjects did not report at least one headache episode during the previous 6 months (i.e. headache-free). All 48 athletes successfully covered the 21.1 km distance. Serum concentration of CGRP significantly increased by 1.5-fold in the entire group, as well as in the headache-positive and headache-free cohorts. Univariate Spearman’s correlation revealed that post-run variation of serum CGRP was significantly and inversely associated with running time (r = −0.30; p = 0.036).

Conclusions

The serum concentration of CGRP is significantly enhanced by medium-distance endurance exercise and the post-exercise increase is dependent on running intensity. Accordingly, high-exercise intensity might be directly related to triggering both exertional headache and/or migraine episodes.

  • 1.

    Collaborators GBDH. Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018;17:954–76.

    • Crossref
    • PubMed
    • Export Citation
  • 2.

    Burch RC, Loder S, Loder E, Smitherman TA. The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache 2015;55:21–34.

    • Crossref
    • PubMed
    • Export Citation
  • 3.

    Amin FM, Aristeidou S, Baraldi C, Czapinska-Ciepiela EK, Ariadni DD, Di Lenola D, et al. The association between migraine and physical exercise. J Headache Pain 2018;19:83.

    • Crossref
    • PubMed
    • Export Citation
  • 4.

    Ahn AH. Why does increased exercise decrease migraine? Curr Pain Headache Rep 2013;17:379.

    • Crossref
    • PubMed
    • Export Citation
  • 5.

    Lippi G, Mattiuzzi C, Sanchis-Gomar F. Physical exercise and migraine: for or against? Ann Transl Med 2018;6:181.

    • Crossref
    • PubMed
    • Export Citation
  • 6.

    Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1–211.

  • 7.

    Hanashiro S, Takazawa T, Kawase Y, Ikeda K. Prevalence and clinical hallmarks of primary exercise headache in middle-aged Japanese on health check-up. Intern Med 2015;54:2577–81.

    • Crossref
    • PubMed
    • Export Citation
  • 8.

    Tofangchiha S, Rabiee B, Mehrabi F. A study of exertional headache’s prevalence and characteristics among conscripts. Asian J Sports Med 2016;7:e30720.

    • PubMed
    • Export Citation
  • 9.

    Chen SP, Fuh JL, Lu SR, Wang SJ. Exertional headache – a survey of 1963 adolescents. Cephalalgia 2009;29:401–7.

    • Crossref
    • PubMed
    • Export Citation
  • 10.

    Edvinsson L, Warfvinge K. Recognizing the role of CGRP and CGRP receptors in migraine and its treatment. Cephalalgia 2019;39:366–73.

    • Crossref
    • PubMed
    • Export Citation
  • 11.

    Khan S, Olesen A, Ashina M. CGRP, a target for preventive therapy in migraine and cluster headache: Systematic review of clinical data. Cephalalgia 2019;39:374–89.

    • Crossref
    • PubMed
    • Export Citation
  • 12.

    Snoer A, Vollesen AL, Beske RP, Guo S, Hoffmann J, Fahrenkrug J, et al. Calcitonin-gene related peptide and disease activity in cluster headache. Cephalalgia 2019;39:575–84.

    • Crossref
    • PubMed
    • Export Citation
  • 13.

    Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies – successful translation from bench to clinic. Nat Rev Neurol 2018;14:338–50.

    • Crossref
    • PubMed
    • Export Citation
  • 14.

    Edvinsson L. Role of CGRP in migraine. Handb Exp Pharmacol 2019;255:121–30.

  • 15.

    Lippi G, Schena F. Run for Science (R4S): the history of a successful project of precision and laboratory medicine in sport and exercise. J Lab Precis Med 2017;2:11.

    • Crossref
    • Export Citation
  • 16.

    Koppen H, van Veldhoven PL. Migraineurs with exercise-triggered attacks have a distinct migraine. J Headache Pain 2013;14:99.

    • Crossref
    • PubMed
    • Export Citation
  • 17.

    Sandoe CH, Kingston W. Exercise headache: a review. Curr Neurol Neurosci Rep 2018;18:28.

    • Crossref
    • PubMed
    • Export Citation
  • 18.

    Tepper SJ. History and review of anti-calcitonin gene-related peptide (CGRP) therapies: from translational research to treatment. Headache 2018;58(Suppl 3):238–75.

    • Crossref
    • PubMed
    • Export Citation
  • 19.

    Wyon Y, Hammar M, Theodorsson E, Lundeberg T. Effects of physical activity and acupuncture on calcitonin gene-related peptide immunoreactivity in different parts of the rat brain and in cerebrospinal fluid, serum and urine. Acta Physiol Scand 1998;162:517–22.

    • Crossref
    • PubMed
    • Export Citation
  • 20.

    Parnow A, Gharakhanlou R, Gorginkaraji Z, Rajabi S, Eslami R, Hedayati M, et al. Effects of endurance and resistance training on calcitonin gene-related peptide and acetylcholine receptor at slow and fast twitch skeletal muscles and sciatic nerve in male wistar rats. Int J Pept 2012;2012:962651.

    • PubMed
    • Export Citation
  • 21.

    Parnow AH, Gharakhanlou R, Eslami R. Effects of physical activity on calcitonin gene-related peptide content at trigeminal ganglion nerve in wistar rats. J Mazand Univ Med Sci 2012;22:25–31.

  • 22.

    Jonhagen S, Ackermann P, Saartok T, Renstrom PA. Calcitonin gene related peptide and neuropeptide Y in skeletal muscle after eccentric exercise: a microdialysis study. Br J Sports Med 2006;40:264–7; discussion 264–7.

    • Crossref
    • PubMed
    • Export Citation
  • 23.

    Goadsby PJ, Edvinsson L. Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies. Brain 1994;117(Pt 3): 427–34.

    • Crossref
    • Export Citation
  • 24.

    Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 1993;33:48–56.

    • Crossref
    • PubMed
    • Export Citation
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