title: Trigeminal antinociception induced by bicuculline in the periaqueductal gray (PAG) is not affected by PAG P/Q-type calcium channel blockade in rat.
abstract: We have recently shown that injection of the P/Q-type (Ca(v)2.1/alpha(1A)) calcium channel blocker, omega-agatoxin IVA, into the periaqueductal gray (PAG) facilitates meningeal dural stimulation-evoked trigeminal nociceptive processing. We injected the GABA(A) antagonist bicuculline into the PAG in addition to the agatoxin and observed bicuculline's effect on neurons responding to dural stimulation recorded in the trigeminal nucleus caudalis of rats in order to determine if P/Q channel-mediated changes acted through GABAergic mechanisms. The inhibition of trigeminal nociceptive neurons characteristic of bicuculline administered into the PAG was maintained in the presence of blocked PAG P/Q-type calcium channels. This suggests the PAG descending pain modulatory pathway is not affected by P/Q-type calcium channel blockade at the postsynaptic GABAergic inhibitory interneuron and the facilitation produced by agatoxin is mediated by another mechanism. These findings have implications for disorders involving the PAG or P/Q-type channels, such as migraine, in particular for the development of preventative treatments, suggesting GABAergic and voltage-gated calcium channels could be separately modulated.
authors.affiliation: Headache Group, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Yolande E
authors.initials: YE
authors.lastname: Knight
authors.forename: Thorsten
authors.initials: T
authors.lastname: Bartsch
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D020865:Calcium Channels, P-Type / Q000187:drug effects*; D020907:Calcium Channels, Q-Type / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D008297:Male; D008845:Microinjections; D008881:Migraine Disorders / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology; D010146:Pain / Q000503:physiopathology; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects / Q000503:physiopathology*; D020867:omega-Agatoxin IVA / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D020867:omega-Agatoxin IVA; D001640:Bicuculline