Inhibition of trigeminovascular dural nociceptive afferents by Ca(2+)-activated K(+) (MaxiK/BK(Ca)) channel opening

Pain
Simon AkermanPeter J Goadsby

Abstract

Migraine is an episodic brain disorder with a significant morbidity. It is thought that activation of trigeminal afferents innervating the dura mater and large cerebral blood vessels is involved in the expression of the disorder. The selective large conductance calcium-activated potassium channels, the BK(Ca) or MaxiK channels, are intrinsic membrane proteins that are widely distributed in the brain. These channels are thought to be involved in controlling neuronal excitability and perhaps transmitter release, possibly in the trigeminocervical complex. We sought to investigate the role of MaxiK/BK(Ca) channels opening in several models of trigeminovascular nociception using NS1619, a benzimidazolone analogue. Intravenously administered NS1619 (10 mg kg(-1)) was able to inhibit neurogenic dural vasodilation (F(4,20)=19.23, P<0.05, n=6). NS1619 (intravenous) was not able to inhibit Aδ-fiber (F(3.01,18.06)=0.79, P=0.52) or C-fiber (F(3.14,18.84)=0.76, P=0.54) afferents in the trigeminal nucleus caudalis and C(1) region of the dorsal horn after dural electrical stimulation, but it was able to inhibit Aδ-fiber afferents after iontophoretic application of NS1619 (t(5)=3.23, P<0.05, n=6) after 5 min. Iontophoresed NS1619 was also able...Continue Reading

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Citations

Oct 11, 2014·Pharmacogenomics·Giovanna GentileMarina Borro
Apr 5, 2014·Headache·Jin Yan, Gregory Dussor
Oct 28, 2014·Frontiers in Physiology·Bo H BentzenMorten Grunnet
May 15, 2013·Cephalalgia : an International Journal of Headache·Simon AkermanJan Hoffmann
May 14, 2014·Cephalalgia : an International Journal of Headache·Cai-Yue LiuBei Ma
Sep 9, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Simon Akerman, Marcela Romero-Reyes
Feb 6, 2014·Expert Review of Clinical Pharmacology·Jan HoffmannPeter J Goadsby
Nov 4, 2016·Physiological Reviews·Ramon LatorreOsvaldo Alvarez
Jan 1, 2019·Brain : a Journal of Neurology·Simon AkermanPeter J Goadsby
Feb 16, 2020·CNS Drugs·Mohammad Al-Mahdi Al-KaragholiMessoud Ashina
May 19, 2020·Cephalalgia : an International Journal of Headache·Sarah L ChristensenJes Olesen
Jul 15, 2021·Cephalalgia : an International Journal of Headache·Simon AkermanMarcela Romero-Reyes
Aug 14, 2021·Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging·Adnan I QureshiCamilo R Gomez

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