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Plasma calcitonin gene-related peptide concentration is comparable to control group among migraineurs and tension-type headache subjects during interictal period: response to comments by Tfelt-Hansen and Ashina
The Journal of Headache and Pain volume 10, pages 387–388 (2009)
Dear Editor,
We thank Drs. Tfelt-Hansen and Ashina [1] for their interest in our article [2]. They have raised a valid point, namely that measurement units should be similar in the scientific literature. We assume that different units mentioned in previous studies were provided by the respective manufacturer of the kit, and we followed the same custom. However, in the interest of uniformity in the literature, as indicated by Drs. Tfelt-Hansen and Ashina, we provide revised results here (Table 1).
A concern was raised regarding the higher inter-ictal concentration of plasma CGRP in the cubital blood than reported in previous studies [3–7]. The available literature provides conflicting results regarding plasma CGRP concentration in migraineurs, both ictal as well as inter-ictal, and even when the blood was collected from different areas (external jugular/internal jugular and cubital) [2–9]. Hence, no conclusion can be reached regarding the baseline concentration of CGRP in plasma. The higher concentration reported in the present study than in previous studies can be explained by a number of methodological factors. First, the CGRP has a very short half life, barely 7 min, hence we made sure that plasma samples were frozen to −70°C within 5 min of drawing the blood [10, 11]. In a number of studies the sample was centrifuged for 15 min [6, 8, 12]. This could have resulted in lower levels. Secondly, it must be remembered that peptides are unstable molecules and they need to be preserved at −70°C. At least in one study samples were stored at –20°C until analysis, and this could have affected the results [13]. Moreover, the plasma level of CGRP follows a circadian pattern and shows troughs and peaks, but at different times according to different studies [14, 15]. We had drawn blood samples between 9 a.m. and 12 noon, when CGRP concentration is highest [14]. Furthermore, sampling methods and anticoagulants may affect the quantitative analysis with some peptides [16]. These factors could have affected the results of previous studies as they used different anticoagulants, e.g. heparin or aprotinin [6, 8, 13]. We used EDTA tubes to collect the blood on the manufacturer’s recommendation. Lastly, the measurement of CGRP is influenced by a number of factors present in the plasma that may cross-react with it (Peninsula Lab Inc., LLC), hence we used the extraction-free kit. This further reduces the chances of error.
The sensitivity of the ELISA kit used in this study was 21 pmol/l and the range was 0–6596 pmol/l (Peninsula Lab Inc., LLC) with intra-assay variation of less than 5%.
Thus, the results of these kinds of studies warrant further studies in this area with better methodologies, until conclusive evidence is yielded.
References
Tfelt-Hansen P, Ashina M (2009) CGRP in migraine. J Headache Pain. doi 10.1007/s10194-009-0139-x
Gupta R, Ahmed T, Banerjee B, Bhatia M (2009) Plasma calcitonin gene-related peptide concentration is comparable to control group among migraineurs and tension type headache subjects during inter-ictal period. J Headache Pain 10:161–166. doi: 10.1007/s10194-009-0110-x, 19277835, 1:CAS:528:DC%2BD1MXls1OksLc%3D
Goadsby PJ, Edvinsson L, Ekman R (1990) Vasoactive peptide release in the extracerebral circulation of humans during migraine attacks. Ann Neurol 28:183–187 1699472, 10.1002/ana.410280213, 1:STN:280:DyaK3M%2FisVSktQ%3D%3D
Tvedskov JF, Lipka K, Ashina M, Iversen HK, Schifter S, Olesen J (2005) No increase of calcitonin gene-related peptide in jugular blood during migraine. Ann Neurol 58:561–563 16178016, 10.1002/ana.20605, 1:CAS:528:DC%2BD2MXhtFGrsL7O
Ashina M, Bendtsen L, Jensen R, Schifter S, Olesen J (2000) Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside attacks. Pain 86:133–138 10779670, 10.1016/S0304-3959(00)00232-3, 1:CAS:528:DC%2BD3cXisFGktbg%3D
Gallai V, Sarchielli P, Floridi A, Franceshini M, Codini M, Glioti G et al (1995) Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally. Cephalalgia 15:380–384 10.1046/j.1468-2982.1995.1505384.x
Fusayasu E, Kowa T, Takeshima T, Nakaso K, Nahashima K (2007) Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods. Pain 128:209–214 17123735, 10.1016/j.pain.2006.09.017, 1:CAS:528:DC%2BD2sXis1Oqsbo%3D
Friberg L, Olesen J, Skyhøj Olsen T, Karle A, Ekman R, Fahrenkrug J (1994) Absence of vasoactive peptide release from brain to cerebral circulation during onset of migraine with aura. Cephalalgia 14:47–54 7515329, 10.1046/j.1468-2982.1994.1401047.x, 1:STN:280:DyaK2c3lvVOjsw%3D%3D
Sarchielli P, Alberti A, Codini M, Floridi A, Gallai V (2000) Nitric oxide metabolites, prostaglandins and trigeminal vasoactive peptides in internal jugular vein blood during spontaneous migraine attacks. Cephalalgia 20:907–918 11304026, 10.1046/j.1468-2982.2000.00146.x, 1:STN:280:DC%2BD3MvntlSgsg%3D%3D
Kraenzlin ME, Ch’ng JLC, Mulderry PK, Ghatei MA, Bloom R (1985) Infusion of a novel peptide, calcitonin gene-related peptide (CGRP) in man: pharmacokinetics and effects on gastric acid secretion and gastrointestinal hormones. Regul Pept 10:189–197 3922013, 10.1016/0167-0115(85)90013-8, 1:CAS:528:DyaL2MXhsl2rtrw%3D
Struthers AD, Brown MJ, Macdonald DW, Beacham JL, Stevenson JC, Morris HR, MacIntyre I (1986) Human calcitonin gene related peptide: a potent endogenous vasodilator in man. Clin Sci 70:389–393 3486086, 1:CAS:528:DyaL28XitVWju7c%3D
Frese A, Schilgen M, Edvinsson L, Frandsen E, Evers S (2005) Calcitonin gene-related peptide in cervicogenic headache. Cephalalgia 25:700–703 16109051, 10.1111/j.1468-2982.2004.00940.x, 1:STN:280:DC%2BD2Mvkt1agtg%3D%3D
Kruuse C, Frandsen E, Schifter S, Thomsen LL, Birk S, Olesen J (2004) Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache. Cephalalgia 24:547–553 15196297, 10.1111/j.1468-2982.2003.00712.x, 1:STN:280:DC%2BD2cvit12ktg%3D%3D
Wimalwasna SJ (1991) Circadian variation of plasma calcitonin gene related peptide in men. J Neuroendocrinol 3:319–322 10.1111/j.1365-2826.1991.tb00281.x
de los Santos ET, Mazzaferri EL (1991) Calcitonin gene related peptide: 24 h profile and response to volume contraction and expansion in normal men. J Clin Endocrinol Metab 72:1031–1035 10.1210/jcem-72-5-1031
Larsen A, Bronstein IB, Dahl B, Wentzel-Larsen T, Kristofferson EK, Fagerhol MK (2007) Quantification of S100A12 (EN-RAGE) in blood varies with sampling method, heparin and calcium. Scand J Immunol 65:192–201 17257225, 10.1111/j.1365-3083.2006.01875.x, 1:CAS:528:DC%2BD2sXjsVKrsbk%3D
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Gupta, R., Tanzeel, A., Banerjee, B. et al. Plasma calcitonin gene-related peptide concentration is comparable to control group among migraineurs and tension-type headache subjects during interictal period: response to comments by Tfelt-Hansen and Ashina. J Headache Pain 10, 387–388 (2009). https://doi.org/10.1007/s10194-009-0141-3
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DOI: https://doi.org/10.1007/s10194-009-0141-3