De Logu Francesco, Nassini Romina, Landini Lorenzo, Geppetti Pierangelo
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, Headache Center, University of Florence, Florence, Italy.
Handb Exp Pharmacol. 2019;255:65-84. doi: 10.1007/164_2018_145.
The benefit reported in a variety of clinical trials by a series of small molecule antagonists for the calcitonin gene-related peptide (CGRP) receptor, or four monoclonal antibodies against the neuropeptide or its receptor, has underscored the release of CGRP from terminals of primary sensory neurons, including trigeminal neurons, as one of the major mechanisms of migraine headaches. A large variety of excitatory ion channels and receptors have been reported to elicit CGRP release, thus proposing these agonists as migraine-provoking agents. On the other side, activators of inhibitory channels and receptors may be regarded as potential antimigraine agents. The knowledge of the intracellular pathways underlying the exocytotic process that results in CGRP secretion or its inhibition is, therefore, of importance for understanding how migraine pain originates and how to treat the disease.
一系列针对降钙素基因相关肽（CGRP）受体的小分子拮抗剂，或四种针对该神经肽或其受体的单克隆抗体，在各种临床试验中报告的益处，突出了初级感觉神经元（包括三叉神经元）末梢释放CGRP是偏头痛的主要机制之一。据报道，多种兴奋性离子通道和受体可引发CGRP释放，因此将这些激动剂视为偏头痛诱发剂。另一方面，抑制性通道和受体的激活剂可被视为潜在的抗偏头痛药物。因此，了解导致CGRP分泌或其抑制的胞吐过程的细胞内途径，对于理解偏头痛疼痛的起源以及如何治疗该疾病至关重要。
