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Altered activity in the nucleus raphe magnus underlies cortical hyperexcitability and facilitates trigeminal nociception in a rat model of medication overuse headache

Authors
  • Potewiratnanond, Prangtip1
  • le Grand, Supang Maneesri2
  • Srikiatkhachorn, Anan3
  • Supronsinchai, Weera4
  • 1 Chulalongkorn University, Interdisciplinary Program of Physiology, Graduate School, Bangkok, Thailand , Bangkok (Thailand)
  • 2 Chulalongkorn University, Department of Pathology, Faculty of Medicine, Bangkok, Thailand , Bangkok (Thailand)
  • 3 King Mongkut’s Institute of Technology Ladkrabang, Faculty of Medicine, Bangkok, Thailand , Bangkok (Thailand)
  • 4 Chulalongkorn University, Department of Physiology, Faculty of Dentistry, Bangkok, Thailand , Bangkok (Thailand)
Type
Published Article
Journal
BMC Neuroscience
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Oct 21, 2019
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12868-019-0536-2
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundThe pathogenesis of medication overuse headache (MOH) involves hyperexcitability of cortical and trigeminal neurons. Derangement of the brainstem modulating system, especially raphe nuclei may contribute to this hyperexcitability. The present study aimed to investigate the involvement of the nucleus raphe magnus (NRM) in the development of cortical and trigeminal hyperexcitability in a rat model of MOH.ResultsChronic treatment with acetaminophen increased the frequency of cortical spreading depression (CSD) and the number of c-Fos-immunoreactive (Fos-IR) neurons in the trigeminal nucleus caudalis (TNC). In the control group, muscimol microinjected into the NRM increased significantly the frequency of CSD-evoked direct current shift and Fos-IR neurons in the TNC. This facilitating effect was not found in rats with chronic acetaminophen exposure. In a model of migraine induced by intravenous systemic infusion of nitroglycerin (NTG), rats with chronic exposure to acetaminophen exhibited significantly more frequent neuronal firing in the TNC and greater Fos-IR than those without the acetaminophen treatment. Muscimol microinjection increased neuronal firing in the TNC in control rats, but not in acetaminophen-treated rats. The number of Fos-IR cells in TNC was not changed significantly.ConclusionChronic exposure to acetaminophen alters the function of the NRM contributing to cortical hyperexcitability and facilitating trigeminal nociception.

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