title: Altered brainstem auditory evoked potentials in a rat central sensitization model are similar to those in migraine.
abstract: Migraine symptoms often include auditory discomfort. Nitroglycerin (NTG)-triggered central sensitization (CS) provides a rodent model of migraine, but auditory brainstem pathways have not yet been studied in this example. Our objective was to examine brainstem auditory evoked potentials (BAEPs) in rat CS as a measure of possible auditory abnormalities. We used four subdermal electrodes to record horizontal (h) and vertical (v) dipole channel BAEPs before and after injection of NTG or saline. We measured the peak latencies (PLs), interpeak latencies (IPLs), and amplitudes for detectable waveforms evoked by 8, 16, or 32 kHz auditory stimulation. At 8 kHz stimulation, vertical channel positive PLs of waves 4, 5, and 6 (vP4, vP5, and vP6), and related IPLs from earlier negative or positive peaks (vN1-vP4, vN1-vP5, vN1-vP6; vP3-vP4, vP3-vP6) increased significantly 2h after NTG injection compared to the saline group. However, BAEP peak amplitudes at all frequencies, PLs and IPLs from the horizontal channel at all frequencies, and the vertical channel stimulated at 16 and 32 kHz showed no significant/consistent change. For the first time in the rat CS model, we show that BAEP PLs and IPLs ranging from putative bilateral medial superior olivary nuclei (P4) to the more rostral structures such as the medial geniculate body (P6) were prolonged 2h after NTG administration. These BAEP alterations could reflect changes in neurotransmitters and/or hypoperfusion in the midbrain. The similarity of our results with previous human studies further validates the rodent CS model for future migraine research.
authors.affiliation: Molecular Neurology Program, Huntington Medical Research Institutes, 99 North El Molino Avenue, Pasadena, CA 91101, USA. Electronic address: xianghong@hmri.org.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Arakaki
authors.affiliation: Mental Retardation Research Center, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Galbraith
authors.affiliation: Neural Engineering Program, Huntington Medical Research Institutes, 734 Fair mount Avenue, Pasadena, CA 91101, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Pikov
authors.affiliation: Molecular Neurology Program, Huntington Medical Research Institutes, 99 North El Molino Avenue, Pasadena, CA 91101, USA.
authors.forename: Alfred N
authors.initials: AN
authors.lastname: Fonteh
authors.affiliation: Molecular Neurology Program, Huntington Medical Research Institutes, 99 North El Molino Avenue, Pasadena, CA 91101, USA. Electronic address: mghworks@hmri.org.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Harrington
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D059333:Central Nervous System Sensitization / Q000187:drug effects; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D008297:Male; D008881:Migraine Disorders / Q000503:physiopathology*; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D005996:Nitroglycerin
keywords: Brainstem auditory evoked potential; Migraine; Nitroglycerin