title: Effects of intravenous metamizole on ongoing and evoked activity of dura-sensitive thalamic neurons in rats.
abstract: Migraine and tension-type headache (TTH) are the most common forms of primary headaches. A general key mechanism underlying development of both the diseases is the trigeminal system activation associated with the ascending nociceptive transmission via the trigemino-thalamo-cortical pathway. The ventroposteromedial (VPM) nucleus is a key thalamic structure, receiving afferent inflow from the craniofacial region; it holds the third-order neurons responsible for conveying sensory information from the extra- and intracranial nociceptors to the cortex. The VPM is currently seen as a therapeutic target for various antimigraine medications, which is shown to reduce the VPM neuronal excitability. A non-opioid analgesic metamizole is widely used in some countries for acute treatment of migraine or TTH. However, the precise mechanisms underlying anticephalgic action of metamizole remain unclear. The objective of our study performed in the rat model of trigemino-durovascular nociception was to evaluate the effects of intravenously administered metamizole on ongoing and evoked firing of the dura-sensitive VPM neurons. The experiments were carried out on rats under urethane-chloralose anesthesia. Cumulative administration of metamizole (thrice-repeated intravenous infusion of 150 mg/kg performed 30 min apart) in 56% of cases produced a suppression of both the ongoing activity of the thalamic VPM neurons and their responses to dural electrical stimulation. Although the inhibitory effect was prevailing, a number of VPM neurons were indifferent to the administration of metamizole. These data suggest that one of the main components of neural mechanism underlying anticephalgic action of metamizole is suppression of the thalamo-cortical nociceptive transmission associated with trigemino-vascular activation.
authors.affiliation: Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, St. Petersburg 199034, Russia; Department of Neuropharmacology, Valdman Institute of Pharmacology, First St. Petersburg Pavlov State Medical University, 6/8 Lev Tolstoy Street, St. Petersburg 197022, Russia. Electronic address: alexey.y.sokolov@gmail.com.
authors.forename: Alexey Y
authors.initials: AY
authors.lastname: Sokolov
authors.affiliation: Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, St. Petersburg 199034, Russia; Department of Neuropharmacology, Valdman Institute of Pharmacology, First St. Petersburg Pavlov State Medical University, 6/8 Lev Tolstoy Street, St. Petersburg 197022, Russia. Electronic address: olga@kolt.infran.ru.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Lyubashina
authors.affiliation: Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, St. Petersburg 199034, Russia. Electronic address: AVANS_d@mail.ru.
authors.forename: Ivan B
authors.initials: IB
authors.lastname: Sivachenko
authors.affiliation: Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, St. Petersburg 199034, Russia; Department of Neuropharmacology, Valdman Institute of Pharmacology, First St. Petersburg Pavlov State Medical University, 6/8 Lev Tolstoy Street, St. Petersburg 197022, Russia. Electronic address: panteleev@kolt.infran.ru.
authors.forename: Sergey S
authors.initials: SS
authors.lastname: Panteleev
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D004177:Dipyrone / Q000008:administration & dosage* / Q000494:pharmacology*; D004388:Dura Mater / Q000502:physiology*; D004558:Electric Stimulation; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D059225:Nociception / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000166:cytology* / Q000502:physiology
chemical_list: D004177:Dipyrone
keywords: Metamizole; Migraine; Neuronal activity; Tension-type headache; Thalamus; Trigemino-vascular system