Sumatriptan alleviates nitroglycerin-induced mechanical and thermal allodynia in mice
T Nikai
Department of Anaesthesiology, Shimane University, Izumo, Japan,
Anatomy and
Search for more papers by this authorKC Brennan
Department of Neurology, University of California Los Angeles, Los Angeles, CA and
Search for more papers by this authorY-H Fu
Departments of Neurology,
Howard Hughes Medical Institute, Chevy Chase, MD, USA, and
Search for more papers by this authorAC Charles
Department of Neurology, University of California Los Angeles, Los Angeles, CA and
Search for more papers by this authorAI Basbaum
Anatomy and
Physiology, University of California San Francisco,
W. M. Keck Foundation Center for Integrative Neuroscience, San Francisco
Search for more papers by this authorLJ Ptáček
Departments of Neurology,
Howard Hughes Medical Institute, Chevy Chase, MD, USA, and
Search for more papers by this authorCorresponding Author
AH Ahn
Departments of Neurology,
Anatomy and
Andrew H Ahn MD, PhD, 1550 4th Street, UCSF Box 2722, San Francisco, CA 94158, USA. Tel. + 1-415-476-3557, fax + 1-415-476-1974, e-mail [email protected]; Louis J Ptáček MD, 1550 4th Street, UCSF Box 2292, San Francisco, CA 94158, USA. Tel. + 1-415-502-5614, fax + 1-415-502-5641, e-mail [email protected]Search for more papers by this authorT Nikai
Department of Anaesthesiology, Shimane University, Izumo, Japan,
Anatomy and
Search for more papers by this authorKC Brennan
Department of Neurology, University of California Los Angeles, Los Angeles, CA and
Search for more papers by this authorY-H Fu
Departments of Neurology,
Howard Hughes Medical Institute, Chevy Chase, MD, USA, and
Search for more papers by this authorAC Charles
Department of Neurology, University of California Los Angeles, Los Angeles, CA and
Search for more papers by this authorAI Basbaum
Anatomy and
Physiology, University of California San Francisco,
W. M. Keck Foundation Center for Integrative Neuroscience, San Francisco
Search for more papers by this authorLJ Ptáček
Departments of Neurology,
Howard Hughes Medical Institute, Chevy Chase, MD, USA, and
Search for more papers by this authorCorresponding Author
AH Ahn
Departments of Neurology,
Anatomy and
Andrew H Ahn MD, PhD, 1550 4th Street, UCSF Box 2722, San Francisco, CA 94158, USA. Tel. + 1-415-476-3557, fax + 1-415-476-1974, e-mail [email protected]; Louis J Ptáček MD, 1550 4th Street, UCSF Box 2292, San Francisco, CA 94158, USA. Tel. + 1-415-502-5614, fax + 1-415-502-5641, e-mail [email protected]Search for more papers by this authorAbstract
The association between the clinical use of nitroglycerin (NTG) and headache has led to the examination of NTG as a model trigger for migraine and related headache disorders, both in humans and laboratory animals. In this study in mice, we hypothesized that NTG could trigger behavioural and physiological responses that resemble a common manifestation of migraine in humans. We report that animals exhibit a dose-dependent and prolonged NTG-induced thermal and mechanical allodynia, starting 30–60 min after intraperitoneal injection of NTG at 5–10 mg/kg. NTG administration also induced Fos expression, an anatomical marker of neuronal activity in neurons of the trigeminal nucleus caudalis and cervical spinal cord dorsal horn, suggesting that enhanced nociceptive processing within the spinal cord contributes to the increased nociceptive behaviour. Moreover, sumatriptan, a drug with relative specificity for migraine, alleviated the NTG-induced allodynia. We also tested whether NTG reduces the threshold for cortical spreading depression (CSD), an event considered to be the physiological substrate of the migraine aura. We found that the threshold of CSD was unaffected by NTG, suggesting that NTG stimulates migraine mechanisms that are independent of the regulation of cortical excitability.
Supporting Information
Supplemental Data Cardiovascular monitoring after NTG injection does not reveal haemodynamically significant changes.
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