Skip to main content

Advertisement

Log in

Interictal levels of calcitonin gene related peptide in gingival crevicular fluid of chronic migraine patients

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Calcitonin gene related peptide (CGRP) is a mediator of neurogenic inflammation playing a major role in the pathogenesis of migraine. Increases in serum CGRP have been detected previously in migraineurs and a return to baseline values regarded as successful treatment. As gingival crevicular fluid is known to originate from the serum, the aim of this study is to measure the CGRP content of gingival crevicular fluid (GCF) in chronic migraine patients and to determine whether there is a correlation between serum and GCF values of CGRP. For this study, 24 female individuals suffering from chronic migraine with aura were age-matched with 15 healthy individuals. Serum and GCF samples were obtained from both groups and enzyme linked immunosorbent assay performed to measure CGRP concentration. The level of CGRP in the serum and GCF of chronic migraine patients was 41 ± 16 pg/mL and 0.25 ± 0.09 pg/μg respectively while in healthy individuals CGRP levels were 29 ± 8 pg/mL and 0.19 ± 0.07 pg/μg. The correlation between CGRP levels of the GCF and serum was 0.88 for migraineurs and 0.81 in the controls. Only a weak positive relationship was observed between age and CGRP levels in both groups. CGRP levels were higher in migraineurs compared with controls both in serum and GCF. Furthermore there is a strong correlation between CGRP levels of the serum and GCF. The results of this study suggest that CGRP levels of GCF have potential diagnostic purposes in patients with chronic migraine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Stewart WF, Lipton RB, Celentano DD, Reed ML (1992) Prevalence of migraine headache in the United States: relation to age, income, race and other sociodemographic factors. JAMA 267:64–69

    Article  PubMed  CAS  Google Scholar 

  2. Moskowitz MA (1991) The visceral organ brain: implications for the pathophysiology of vascular head pain. Neurology 41:182–186

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. Goadsby PJ, Edvisnson L, Ekman R (1990) Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 28:183–187

    Article  PubMed  CAS  Google Scholar 

  5. Edvinsson L, Uddman R (2005) Neurobiology in primary headaches. Brain Res Brain Res Rev 48:438–456

    Article  PubMed  Google Scholar 

  6. Li J, Vause CV, Durham PL (2008) Calcitonin gene-related peptide stimulation of nitric oxide synthesis and release from trigeminal ganglion glial cells. Brain Res 1196:22–32

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Goadsby PJ, Edvinsson L (1994) Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attack therapies. Brain 117:427–434

    Article  PubMed  Google Scholar 

  8. Cernuda-Morollón E, Larrosa D, Ramón C et al (2013) Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology 81:1191–1196

    Article  PubMed  CAS  Google Scholar 

  9. Ashina M, Bendtsen L, Jensen R, Schifter S, Jansen-Olesen I, Olesen J (2000) Plasma levels of calcitonin gene-related peptide in chronic tension-type headache. Neurology 55:1335–1340

    Article  PubMed  CAS  Google Scholar 

  10. Frese A, Schilgen M, Edvinsson L, Frandsen E, Evers S (2005) Calcitonin gene-related peptide in cervicogenic headache. Cephalalgia 25:700–703

    Article  PubMed  CAS  Google Scholar 

  11. Cady RK, Vause CV, Ho TW, Bigal ME, Durham PL (2009) Elevated saliva calcitonin gene-related peptide levels during acute migraine predict therapeutic response to rizatriptan. Headache: J Head Face Pain 49:1258–1266

    Article  Google Scholar 

  12. Jang MU, Park JW, Kho HS, Chung SC, Chung JW (2011) Plasma and saliva levels of nerve growth factor and neuropeptides in chronic migraine patients. Oral Dis 17:187–193

    Article  PubMed  Google Scholar 

  13. Kaufman E, Lamster IB (2002) The diagnostic applications of saliva—a review. CROBM 13:197–212

    Google Scholar 

  14. Leppilahti JM, Hernández-Ríos PA, Gamonal JA, Tervahartiala T, Brignardello-Petersen R, Mantyla P, Sorsa T, Hernández M (2014) Matrix metalloproteinases and myeloperoxidase in gingival crevicular fluid provide site-specific diagnostic value for chronic periodontitis. J Clin Periodontol 41:348–356

    Article  PubMed  CAS  Google Scholar 

  15. Ehlers V, Willershausen I, Kraft J, Münzel T, Willershausen B (2011) Gingival crevicular fluid MMP-8-concentrations in patients after acute myocardial infarction. Head Face Med 7:1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Yamaguchi M, Takada R, Kambe S, Hatakeyama T, Naitoh K, Yamazaki K, Kobayashi M (2005) Evaluation of time-course changes of gingival crevicular fluid glucose levels in diabetics. Biomed Microdevices 7:53–58

    Article  PubMed  CAS  Google Scholar 

  17. Noguchi E, Kato R, Ohno K, Mitsui A, Obama T, Hirano T, Itabe H, Yamamoto M (2014) The apolipoprotein B concentration in gingival crevicular fluid increases in patients with diabetes mellitus. Clin Biochem 47:67–71

    Article  PubMed  CAS  Google Scholar 

  18. Awawdeh LA, Lundy FT, Linden GJ, Shaw C, Kennedy JG, Lamey PJ (2002) Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in gingival crevicular fluid associated with painful human teeth. Eur J Oral Sci 110:185–191

    Article  PubMed  CAS  Google Scholar 

  19. Lundy FT, Shaw C, McKinnell J, Lamey PJ, Linden GJ (1999) Calcitonin gene-related peptide in gingival crevicular fluid in periodontal health and disease. J Clin Periodontol 26:212–216

    Article  PubMed  CAS  Google Scholar 

  20. Cernuda-Morollón E, Ramón C, Martínez-Camblor P, Serrano-Pertierra E, Larrosa D, Pascual J (2015) OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine. Pain 156:820–824

    Article  PubMed  CAS  Google Scholar 

  21. Becerik S, Ozçaka O, Nalbantsoy A et al (2010) Effects of menstrual cycle on periodontal health and gingival crevicular fluid markers. J Periodontol 81:673–681

    Article  PubMed  CAS  Google Scholar 

  22. Sardarian A, Andisheh Tadbir A, Zal F, Amini F, Jafarian A, Khademi F, Mostafavi-Pour Z (2015) Altered oxidative status and integrin expression in cyclosporine A-treated oral epithelial cells. Toxicol Mech Methods 25:98–104

    Article  PubMed  CAS  Google Scholar 

  23. Bigal ME, Liberman JN, Lipton RB (2006) Age-dependent prevalence and clinical features of migraine. Neurology 67:246–251

    Article  PubMed  Google Scholar 

  24. Koka S, Beebe TJ, Merry SP, DeJesus RS, Berlanga LD, Weaver AL, Montori VM, Wong DT (2008) The preferences of adult outpatients in medical or dental care settings for giving saliva, urine or blood for clinical testing. J Am Dent Assoc 139:735–740

    Article  PubMed  PubMed Central  Google Scholar 

  25. Diener HC, Charles A, Goadsby PJ, Holle D (2015) New therapeutic approaches for the prevention and treatment of migraine. Lancet Neurol 14:1010–1022

    Article  PubMed  CAS  Google Scholar 

  26. Edvinsson L (2015) The journey to establish CGRP as a migraine target: a retrospective view. Headache 55:1249–1255

    Article  PubMed  Google Scholar 

  27. Edvinsson L (2015) CGRP receptor antagonists and antibodies against CGRP and its receptor in migraine treatment. Br J Clin Pharmacol 80:193–199

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Wrobel Goldberg S, Silberstein SD (2015) Targeting CGRP: a new era for migraine treatment. CNS Drugs 29:443–452

    Article  PubMed  CAS  Google Scholar 

  29. Bigal ME, Walter S, Rapoport AM (2015) Therapeutic antibodies against CGRP or its receptor. Br J Clin Pharmacol 79:886–895

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Barbanti P, Aurilia C, Fofi L, Egeo G, Ferron P (2017) The role of anti-CGRP antibodies in the pathophysiology of primary headaches. Neurol Sci 38(Supplement 1):31–35

    Article  PubMed  Google Scholar 

  31. Giamberardino MA, Affaitati G, Curto M, Negro A, Costantini A (2016) Martelletti P (2016) Anti-CGRP monoclonal antibodies in migraine: current perspectives. Intern Emerg Med 11:1045–1057

    Article  PubMed  Google Scholar 

  32. Paemeleire K, MaassenVanDenBrink A (2018) Alcitonin-gene-related peptide pathway mAbs and migraine prevention. Curr Opin Neurol. https://doi.org/10.1097/WCO.0000000000000548

  33. Maasumi K, Tepper SJ, Rapoport AM (2017) New treatments for headache. Neurol Sci 38(Supplement 1):145–156

    Article  PubMed  Google Scholar 

Download references

Funding

The authors of the manuscript would like to thank the vice chancellery of the AJA University of Medical Sciences for the funding of this research (grant number: 2274). We would also like to thank Shiraz University of Medical sciences for their support and facilitation in the process of patient selection and sampling.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ahmadreza Sardarian.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fekrazad, R., Sardarian, A., Azma, K. et al. Interictal levels of calcitonin gene related peptide in gingival crevicular fluid of chronic migraine patients. Neurol Sci 39, 1217–1223 (2018). https://doi.org/10.1007/s10072-018-3340-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-018-3340-3

Keywords

Navigation