Several lines of evidence suggest a major role of calcitonin gene-related 
peptide (CGRP) in the pathogenesis of migraine and other primary headaches. 
Inhibition of CGRP receptors by olcegepant and telcagepant has been successfully 
used to treat acute migraine and to reduce the activity of spinal trigeminal 
neurons involved in meningeal nociception in rodents. The site of CGRP receptor 
inhibition is unclear, however. In adult Wistar rats anaesthetized with 
isofluorane systemic intravenous infusion (0.9 mg/kg) or unilateral facial 
injection (1 mM in 100 microl) of capsaicin was used to induce activity in the 
trigeminal nociceptive system. Animals were pre-treated either by saline or 
olcegepant. In comparison with vehicle infusion or the non-injected side of the 
face, capsaicin significantly increased the expression of the activation markers 
Fos in the spinal trigeminal nucleus and phosphorylated extracellular 
signal-regulated kinase in the trigeminal ganglion. Pre-treatment with 
olcegepant (900 microg/kg) inhibited the capsaicin-induced expression of Fos 
throughout the spinal trigeminal nucleus by 57%. In contrast, the expression of 
phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion 
was not changed by olcegepant pre-treatment. CGRP receptor inhibition, which has 
been shown to decrease spinal trigeminal activity, is likely to occur in the 
central nervous system rather than in the periphery including the trigeminal 
ganglion. This may be important for future therapeutic interventions with CGRP 
receptor antagonists in migraine.