Calcitonin Gene-Related Peptide mRNA Synthesis in Trigeminal Ganglion Neurons after Cortical Spreading Depolarization.

Migraine is a debilitating neurovascular disorder characterized by recurrent headache attacks of moderate to severe intensity. Calcitonin gene-related peptide (GGRP), which is abundantly expressed in trigeminal ganglion (TG) neurons, plays a crucial role in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, activates the trigeminovascular system. In the present study, we investigated mRNA expression in TG neurons in a CSD-based mouse migraine model. Our in situ hybridization analysis showed that mRNA expression was observed in smaller-sized neuronal populations. CSD did not significantly change the density of mRNA-synthesizing neurons in the ipsilateral TG. However, the cell sizes of mRNA-synthesizing TG neurons were significantly larger in the 48 h and 72 h post-CSD groups than in the control group. The proportions of mRNA-synthesizing TG neurons bearing cell diameters less than 14 μm became significantly less at several time points after CSD. In contrast, we found significantly greater proportions of mRNA-synthesizing TG neurons bearing cell diameters of 14-18 μm at 24 h, 48, and 72 h post-CSD. We deduce that the CSD-induced upward cell size shift in mRNA-synthesizing TG neurons might be causative of greater disease activity and/or less responsiveness to CGRP-based therapy.