Transcriptional analysis of trigeminal ganglia in a CFA-induced rat orofacial pain model

Although several underlying pathophysiological processes have been explored, the origin and precise pathomechanism of migraine are still being debated. Inflammatory pathways have been suggested to play role in migraine, trigeminal nociceptor sensitisation, thereby causing hyperalgesia and allodynia. The aim of the present study was to investigate gene expression changes in trigeminal ganglia (TRG), central trigeminal nucleus caudalis (TNC) and peripheral blood mononuclear cells (PBMC) evoked by Complete Freund’s Adjuvant (CFA) induced peripheral inflammation. 512 differentially expressed genes were found between CFA-treated and contralateral TRG samples 7 days after CFA injection. The mRNA expression changes of G-protein coupled receptor 39 (Gpr39), kisspeptin-1 receptor (Kiss1r), kisspeptin (Kiss1) and Lkaaear1 were selected for validation. They were most upregulated on day 3 in TRGs of the CFA-treated side. CFA-induced significant orofacial mechanical allodynia in one day with a maximum on day 3. This correlated with patterns of neuronal (Fosb), glial (Iba1), and astrocyte (Gfap) activation markers in both TRG and TNC, and surprisingly in PBMCs. Similar transcriptional changes of Cgrp, the well-known key molecule in migraine pathophysiology, were also revealed. In TNCs, gene expression changes similar to TRGs were observed but Kiss1r transcripts were not significantly altered while Neurod2 was observed only in TNC. These results could indicate the involvement of Gpr39, Kiss1r and synaptic plasticity associated Lkaaear1, Neurod2 genes in the cascade of events resulting in the sensitization underlying migraine headache and the accompanying facial allodynia. Orofacial inflammation was induced by unilateral s.c. injection of 50 µl complete Freund's adjuvant (CFA; 1 mg/ml) into the whisker pad of male rats (n=8). After 7 days, trigeminal ganglia tissue were excised from both sides of each animal (control and treated side). 15 RNA samples were sent for microarray analysis.