Sphenopalatine Ganglion (SPG) may be where CGRP monoclonal antibodies work. They do not pass into brain.  This new study helps explain why a simple inexpensive SPG Block may be as effective or more effective than CGRP medications.   This new study utilized Fluorescently-labeled fremanezumab and found it was not in the brain proper but rather found peripherally. It does not pass healthy Blood-Brain barrier.

This research concluded “Our inability to detect fluorescent (CGRP-mAbs) in the brain supports the conclusion that CGRP-mAbs prevent the headache phase of migraine by acting mostly, if not exclusively, outside the brain as the amount of CGRP-mAbs that enters the brain (if any) is too small to be physiologically meaningful.”

Where did this medication react?

CGRP work in the Sphenopalatine Ganglion, among other peripheral structures.
More specifically in “dura, dural blood vessels, trigeminal ganglion, C2 dorsal root ganglion, the parasympathetic sphenopalatine ganglion and the sympathetic superior cervical ganglion but not in the spinal trigeminal nucleus, thalamus, hypothalamus or cortex.”

This research was done in rats because living humans rarely want their brains dissected but is extremely meaningful