title: P/Q-type calcium-channel blockade in the periaqueductal gray facilitates trigeminal nociception: a functional genetic link for migraine?
abstract: The discovery of mis-sense mutations in the alpha1A 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 omega-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 Adelta-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.
authors.affiliation: Headache Group, Institute of Neurology, London, WC1N 3BG, United Kingdom.
authors.forename: Yolande E
authors.initials: YE
authors.lastname: Knight
authors.forename: Thorsten
authors.initials: T
authors.lastname: Bartsch
authors.forename: Holger
authors.initials: H
authors.lastname: Kaube
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020865:Calcium Channels, P-Type / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D008881:Migraine Disorders / Q000209:etiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects / Q000503:physiopathology; D014277:Trigeminal Neuralgia / Q000139:chemically induced* / Q000503:physiopathology; D020867:omega-Agatoxin IVA / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D018756:GABA Antagonists; D020867:omega-Agatoxin IVA