Effects of N-, P/Q- and L-type calcium channel blockers on nociceptive neurones of the trigeminal nucleus with input from the dura.
In anaesthetized rats, extracellular recordings were made from neurones of the spinal trigeminal nucleus, involved in the processing of nociceptive input from the dura. Blockers of voltage-gated calcium channels (VGCCs) were administered topically to the exposed brainstem. Blockade of N-type (CaV2.2) channels reduced spontaneous activity and responses of the neurones to cold and chemical stimuli applied to the dura, suggesting that N-type channels regulate excitatory synaptic activation. Blockade of L-type (CaV1) channels enhanced spontaneous discharges of the neurones. Blockade of P/Q-type (CaV2.1) channels slightly decreased responses to chemical and cold stimuli but markedly increased spontaneous activity, an effect which was absent during concomitant application of GABA to the brainstem. The data suggest that P/Q-type VGCCs regulate a tonic synaptic inhibitory control of the brainstem neurones. The risk of migraine by genetic modifications of P/Q-type channels may thus be sought in disturbed inhibition in the network that processes nociceptive dura input.
Ebersberger
A
A
Department of Physiology, University of Jena, Jena, Germany.
Portz
S
S
Meissner
W
W
Schaible
H-G
HG
Richter
F
F
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000187:drug effects / Q000378:metabolism; D003080:Cold Temperature; D004388:Dura Mater / Q000187:drug effects / Q000502:physiology; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D014278:Trigeminal Nuclei / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type