The Journal of Neuroscience, 2002, 22:RC213:1-6
RAPID COMMUNICATION
P/Q-Type Calcium-Channel Blockade in the Periaqueductal
Gray Facilitates Trigeminal Nociception: A Functional Genetic
Link for Migraine?
Yolande E.
Knight,
Thorsten
Bartsch,
Holger
Kaube, and
Peter J.
Goadsby
Headache Group, Institute of Neurology, London, WC1N 3BG,
United Kingdom
The discovery of mis-sense mutations in the 
1A subunit of the
P/Q-type calcium channel in patients with familial hemiplegic migraine
indicates the potential involvement of dysfunctional ion channels in
migraine. The periaqueductal gray (PAG) region of the brainstem
modulates craniovascular nociception and, through its role in the
descending pain modulation system, may contribute to migraine
pathophysiology. In this study we sought to investigate the possible
link between the genetic mutations found in migraineurs and the PAG as
a modulator of craniovascular nociception. We microinjected the
P/Q-type calcium-channel blocker 
-agatoxin IVA into the rat ventrolateral PAG (vlPAG). We examined its effect on the nociceptive transmission of second-order neurons recorded in the trigeminal nucleus
caudalis and activated by stimulation of the parietal dura
mater. After injection of agatoxin into the vlPAG
(n = 20) responses to dural stimulation were
facilitated by 143% (p < 0.0001) for
A
-fiber activity and 180% for C-fiber activity
(p < 0.05). Similarly, spontaneous
background activity increased by 163% (p < 0.0001). These results demonstrate that P/Q-type calcium channels in
the PAG play a role in modulating trigeminal nociception and suggest a
role for dysfunctional P/Q-type calcium channels in migraine pathophysiology.
Key words:
migraine; electrophysiology; periaqueductal gray; P/Q-type calcium channel; trigeminal; nociception
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