Trigeminal antinociception induced by bicuculline in the periaqueductal gray (PAG) is not affected by PAG P/Q-type calcium channel blockade in rat

doi:10.1016/S0304-3940(02)01250-8

Neuroscience Letters

Volume 336, Issue 2, 16 January 2003, Pages 113-116

https://doi.org/10.1016/S0304-3940(02)01250-8 Get rights and content

Abstract

We have recently shown that injection of the P/Q-type (Ca_v2.1/α_1A) calcium channel blocker, ω-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.

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Acknowledgements

The authors wish to thank Simon Akerman, R. James Storer, Michele Lasalandra, Paul Hammond, Bridget Lumb, Simon McMullan, David Bulmer and Alexandra V Gourine for technical advice and support. The Wellcome Trust and the Migraine Trust supported this work. The Deutsche Forschungsgemeinschaft supported Thorsten Bartsch.

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Trigeminal antinociception induced by bicuculline in the periaqueductal gray (PAG) is not affected by PAG P/Q-type calcium channel blockade in rat

Abstract

Section snippets

Acknowledgements

Prog. Neurobiol.

Brain Res.

Trends Neurosci.

Neuroscience

Distribution of the voltage-dependent calcium channel alpha1G subunit mRNA and protein throughout the mature rat brain

Eur. J. Neurosci.

Distribution of the voltage-dependent calcium channel alpha(1A) subunit throughout the mature rat brain and its relationship to neurotransmitter pathways

J. Comp. Neurol.

The tentorial nerves and localization of intracranial pain in man

Neurology

Migraine: current understanding and treatment

N. Engl. J. Med.