Sumatriptan alleviates nitroglycerin-induced mechanical and thermal allodynia in mice.
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.
Bates
E A
EA
Department of Neurology, University of California, San Francisco, CA 94158, USA.
Nikai
T
T
Brennan
K C
KC
Fu
Y-H
YH
Charles
A C
AC
Basbaum
A I
AI
Ptácek
L J
LJ
Ahn
A H
AH
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D013181:Cortical Spreading Depression / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D005996:Nitroglycerin / Q000633:toxicity*; D010812:Physical Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000187:drug effects; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D018170:Sumatriptan / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000633:toxicity*
D016760:Proto-Oncogene Proteins c-fos; D058829:Serotonin 5-HT1 Receptor Antagonists; D014665:Vasodilator Agents; D018170:Sumatriptan; D005996:Nitroglycerin