title: Predictive validity of endpoints used in electrophysiological modelling of migraine in the trigeminovascular system.
abstract: The trigeminovascular system has a pivotal role in the pathomechanism of migraine. The aim of the present study was to further develop existing models of migraine making them more suitable for testing the effects of compounds with presumed antimigraine activity in anaesthetised rats. Simultaneous recording of ongoing activity of spontaneously active neurons in the trigeminocervical complex as well as their discharges evoked by electrical stimulation of the dura mater via activation of A- and C-sensory fibres were carried out. Effects of sumatriptan, propranolol and topiramate were evaluated prior to and after application of a mixture containing inflammatory mediators on the dura. Propranolol (10 mg/kg s.c) and topiramate (30 mg/kg s.c.) resulted in a tendency to decrease the level of both spontaneous and evoked activity, while sumatriptan (1 mg/kg s.c.) did not exhibit any effect on recorded parameters. Application of an inflammatory soup to the dura mater boosted up spontaneous activity, which could be significantly attenuated by propranolol and topiramate but not by sumatriptan. In addition, all compounds prevented the delayed increase of spontaneous firing. In contrast to the ongoing activity, evoked responses were not augmented by inflammatory mediators. Nevertheless, inhibitory effect of propranolol and topiramate was evident when considering A- or C-fibre responses. Findings do not support the view that electrically evoked responses are useful for the measurement of trigeminal sensitization. It is proposed however, that inhibition of enhanced firing (immediate and/or delayed) evoked by inflammatory mediators as an endpoint have higher predictive validity regarding the clinical effectiveness of compounds.
authors.affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Plc, Gyömrői út 19-21, 1103 Budapest, Hungary. Electronic address: b.farkas@richter.hu.
authors.forename: Bence
authors.initials: B
authors.lastname: Farkas
authors.affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Plc, Gyömrői út 19-21, 1103 Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Kardos
authors.affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Plc, Gyömrői út 19-21, 1103 Budapest, Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Orosz
authors.affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Plc, Gyömrői út 19-21, 1103 Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Tarnawa
authors.affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Plc, Gyömrői út 19-21, 1103 Budapest, Hungary.
authors.forename: Csongor
authors.initials: C
authors.lastname: Csekő
authors.affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Plc, Gyömrői út 19-21, 1103 Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Lévay
authors.affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Plc, Gyömrői út 19-21, 1103 Budapest, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Farkas
authors.affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Plc, Gyömrői út 19-21, 1103 Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Lendvai
authors.affiliation: Pharmacology and Drug Safety Research, Gedeon Richter Plc, Gyömrői út 19-21, 1103 Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Kovács
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018170:Sumatriptan / Q000494:pharmacology* / Q000627:therapeutic use; D000077236:Topiramate; D014276:Trigeminal Nerve / Q000503:physiopathology*; D014278:Trigeminal Nuclei / Q000473:pathology*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D014665:Vasodilator Agents; D000077236:Topiramate; D005632:Fructose; D018170:Sumatriptan; D011433:Propranolol
keywords: Headache; Inflammatory soup; Pain; Rat model; Sensitization