Expression and function of calcitonin gene-related peptide (CGRP) receptors in trigeminal ganglia of R192Q Cacna1a knock-in mice.

摘要: Migraine is a neurovascular brain disorder suggested to be due dysfunction of the trigeminovascular system with sensitization trigeminal ganglion (TG) nociceptors. Since neuropeptide calcitonin gene-related peptide (CGRP) has been established as key player in pathogenesis migraine, CGRP receptor antagonists have considered useful compounds block headache originating from hyperactivation such TG neurons. Whereas there some information on expression receptors postmortem human tissue, data are lacking for migraineurs suffering common or genetic migraine. To help clarify these issues it very study transgenic knock-in (KI) mouse model hemiplegic migraine expressing R192Q missense mutation α1 subunit CaV2.1 calcium channels previously found patients familial type-1 (FHM-1). The aim present study, therefore, was compare and function wildtype (WT) versus KI TG. principal components receptor, namely CLR RAMP-1 proteins, were similarly expressed WT neurons (in situ culture) responded exogenous strong rise cAMP concentration. Hence, reported phenotype not up-regulation but likely caused by constitutively larger release CGRP. This observation implies that, FHM-1 TG, normal sensory neuron signaling can restored once extracellular concentration returns control level targeted treatment.