Hansen Jakob Møller, Fahrenkrug Jan, Petersen Jesper, Wienecke Troels, Olsen Karsten Skovgaard, Ashina Messoud
Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, DK-2600 Copenhagen, Denmark.
Department of Clinical Biochemistry, Bispebjerg Hospital, Faculty of Health Sciences, University of Copenhagen, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark.
Scand J Pain. 2013 Oct 1;4(4):211-216. doi: 10.1016/j.sjpain.2013.04.002.
Background and purpose The origin of migraine pain is still elusive, but increasingly researchers focus on the neuropeptides in the perivascular space of cranial vessels as important mediators of nociceptive input during migraine attacks. The parasympathetic neurotransmitters, pituitary adenylate cyclase activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) may be released from parasympathetic fibres and activate sensory nerve fibres during migraine attacks. Triptans are effective and well tolerated in acute migraine management but the exact mechanism of action is still debated. Triptans might reduce circulating neuropeptides. To examine this question, we examined the effect of sumatriptan on VIP and PACAP levels in vivo, under conditions without trigeminovascular system activation. Methods In 16 healthy volunteers we measured VIP and PACAP levels before and after administration of subcutaneous sumatriptan. We simultaneously collected blood samples from the internal and external jugular, the cubital veins and the radial artery, thereby covering both the cerebral and systemic circulation. VIP and PACAP determinations were assayed blindly with respect to timing and vascular compartments, but with all samples of a patient in the same assay, to minimize the influence of interassay variation. Results We found no difference in VIP and PACAP concentrations between the internal and external jugular, the cubital veins and the radial artery, (P>0.05), and the circulating levels of VIP and PACAP did not change over time (P>0.05). We found excellent agreement between neuropeptide levels in the internal and the external jugular system. Conclusion Sumatriptan did not change the levels of circulating VIP and PACAP in the intra or extra cerebral circulation in healthy volunteers. Under baseline conditions, without trigeminovascular activation, sumatriptan does not affect the release of neuropeptides VIP and PACAP. Implications Our results indicate no effect of 5-HT1B/D receptor activation on circulating levels of VIP and PACAP in humans without trigeminovascular activation. Given that neuropeptides play an important role for migraine it would be interesting to conduct a similar study in a migraine population.
背景与目的 偏头痛疼痛的起源仍不明确，但越来越多的研究人员将注意力集中在颅血管血管周围间隙中的神经肽上，认为它们是偏头痛发作期间伤害性传入的重要介质。副交感神经递质，垂体腺苷酸环化酶激活肽-38（PACAP38）和血管活性肠肽（VIP）可能在偏头痛发作期间从副交感神经纤维释放并激活感觉神经纤维。曲坦类药物在急性偏头痛治疗中有效且耐受性良好，但其确切作用机制仍存在争议。曲坦类药物可能会降低循环中的神经肽水平。为了研究这个问题，我们在未激活三叉神经血管系统的条件下，研究了舒马曲坦对体内VIP和PACAP水平的影响。方法 在16名健康志愿者中，我们测量了皮下注射舒马曲坦前后的VIP和PACAP水平。我们同时从颈内静脉、颈外静脉、肘静脉和桡动脉采集血样，从而涵盖脑循环和体循环。VIP和PACAP的测定在时间和血管腔室方面进行盲法检测，但同一患者的所有样本在同一次检测中进行，以尽量减少检测间差异的影响。结果 我们发现颈内静脉、颈外静脉、肘静脉和桡动脉之间的VIP和PACAP浓度没有差异（P>0.05），并且VIP和PACAP的循环水平随时间没有变化（P>0.05）。我们发现颈内静脉和颈外静脉系统中的神经肽水平之间具有极好的一致性。结论 舒马曲坦没有改变健康志愿者脑内或脑外循环中循环VIP和PACAP的水平。在基线条件下，未激活三叉神经血管系统时，舒马曲坦不影响神经肽VIP和PACAP的释放。意义 我们的结果表明，在未激活三叉神经血管系统的人类中，5-HT1B/D受体激活对VIP和PACAP的循环水平没有影响。鉴于神经肽在偏头痛中起重要作用，在偏头痛人群中进行类似研究将很有趣。
