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 2 hours 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 2 hours 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.

Auditory brainstem function in women with vestibular migraine: a controlled study

“…As previous studies have suggested [33–35], there were no differences in auditory brainstem click responses between groups during the migraine interictal period. However, other authors found significant differences [36, 37].…”

Dynamic sodium imaging at ultra-high field reveals progression in a preclinical migraine model

“…In preclinical rodent models of migraine, NTG-induced central sensitization is a well-characterized model that has demonstrated increased brain sodium levels [24], hypersensitivity to pain based on behavioral response [18,24,28,31,53], altered cerebral blood flow [22,27], increased cFos expression in the trigeminal nucleus caudalis (TNC) [24,54], increased expression of nitric oxide synthase [21,42] and abnormalities in brainstem auditory evoked potentials (BAEPs) of rats [4]. In clinical cohorts, NTG administration triggers a mild immediate headache, which is stronger in migraine sufferers than in healthy subjects and derives from the acute vasodilatory effects of nitric oxide (NO) impacting the cerebral vasculature.…”

Metabolic assessment of a migraine model using relaxation‐enhanced 1H spectroscopy at ultrahigh field

“…There is considerable evidence that the administration of nitric oxide (NO) donors, such as NTG, in humans induces headaches similar to those in migraine attacks (11, 20). As such, NTG-induced sensitization is a widely accepted migraine model in rodents (5,7–9), as well as humans (10). In preclinical models, NTG causes allodynia and hyperalgesia (21), brain sodium elevation and activation of cFos in the trigeminal nucleus caudalis neurons (TNC) (5), and abnormalities in the brain stem auditory evoked potentials of rats (7).…”

“…It follows that the identification of specific metabolic changes may improve understanding of migraine and open new avenues for therapy development. This study, therefore, evaluates biochemical and metabolic imbalances hypothesized to reflect dysfunctional pathways paralleling migraine impacts in humans by means of a frequently studied nitroglycerin (NTG) triggered animal migraine model (5, 7–9). In clinical cohorts, NTG typically triggers a mild headache that is short-lived and stops rapidly after administration is completed, based on a short (2-min) half-life (10, 11).…”