METHODS: In our study, we investigated the projections from the LPBn by performing stereotaxic injections of AAV2/2Retro-hSyn-EGFP (abbreviated as EGFP) into the bed nucleus of the stria terminalis (BNST) and AAV2/2Retro-hSyn-tdTomato (abbreviated as tdTomato) into the central amygdala (CeA) in mice. The animals subsequently underwent spared nerve injury (SNI) surgery on the contralateral side to the AAV injections. To examine the expression of calcitonin gene-related peptide (CGRP) and c-Fos, we conducted immunofluorescent histochemistry.

RESULTS: Our results indicated that approximately 26 % of the LPBn neurons retrogradely labeled with either EGFP or tdTomato were dual-labeled with both markers. Moreover, a significant majority (85.49 %) of these double-labeled neurons were CGRP positive (CGRP+). In mice subjected to SNI, nearly all of these neurons (93.25 %) were c-Fos positive (c-Fos+), indicating that they were activated.

OBJECTIVE: The previous reports on the neuroprotective and GABAA receptor positive modulatory effect of hispidulin may render it as a possible novel candidate as an antimigraine agent.

METHODS: In the present study, we employed the intracisternal instillation of capsaicin in anesthetized rats to induce the activation of trigeminovascular system (TGVS), which mimics the histopathological hallmarks of migraine that include increased neuronal activation in the trigeminal cervical complex (TCC), calcitonin gene-related peptide (CGRP) immunoreactivity in the trigeminal ganglia (TG) and CGRP depletion in the dura mater.

RESULTS: Administration of hispidulin (4, 10, and 50 mg/kg, i.p.) significantly reduced all three TGVS activation parameters induced by i.c. capsaicin. However, pre-treatment of a selective antagonist for α6 subunit-containing GABAA receptor, furosemide (20 mg/kg, i.p.), did not significantly reverse the antimigraine effect of hispidulin.