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Intravenous dextromethorphan/quinidine inhibits activity of dura‐sensitive spinal trigeminal neurons in rats
Author(s) -
Sokolov A.Y.,
Lyubashina O.A.,
Berkovich R.R.,
Panteleev S.S.
Publication year - 2015
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.631
Subject(s) - medicine , anesthesia , nociception , stimulation , migraine , pharmacology , trigeminal ganglion , electrophysiology , spinal trigeminal nucleus , trigeminal nerve , neuroscience , sensory system , psychology , receptor
Background Migraine is a chronic neurological disorder characterized by episodes of throbbing headaches. Practically all medications currently used in migraine prophylaxis have a number of substantial disadvantages and use limitations. Therefore, the further search for principally new prophylactic antimigraine agents remains an important task. The objective of our study was to evaluate the effects of a fixed combination of dextromethorphan hydrobromide and quinidine sulphate ( DM/Q ) on activity of the spinal trigeminal neurons in an electrophysiological model of trigemino‐durovascular nociception. Methods The study was performed in 15 male W istar rats, which were anaesthetized with urethane/α‐chloralose and paralysed using pipecuronium bromide. The effects of cumulative intravenous infusions of DM/Q (three steps performed 30 min apart, 15/7.5 mg/kg of DM/Q in 0.5 mL of isotonic saline per step) on ongoing and dural electrical stimulation‐induced neuronal activities were tested in a group of eight rats over 90 min. Other seven animals received cumulative infusion of equal volumes of saline and served as control. Results Cumulative administration of DM/Q produced steady suppression of both the ongoing activity of the spinal trigeminal neurons and their responses to electrical stimulation of the dura mater. Conclusions It is evident that the observed DM/Q ‐induced suppression of trigeminal neuron excitability can lead to a reduction in nociceptive transmission from meninges to higher centres of the brain. Since the same mechanism is believed to underlie the pharmacodynamics of many well‐known antimigraine drugs, results of the present study enable us to anticipate the potential efficacy of DM/Q in migraine.