Sumatriptan alleviates nitroglycerin-induced mechanical and thermal allodynia in mice

Abstract

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.

Differential Development of Facial and Hind Paw Allodynia in a Nitroglycerin-Induced Mouse Model of Chronic Migraine: Role of Capsaicin Sensitive Primary Afferents

“…Bates et al showed the mechanical allodynia and heat hyperalgesia developed in the hind paw after injection of NTG, which was similar to results in the present study. 3) On the other hand, Galeotti and Ghelardini reported that NO donors NTG and sodium nitroprusside induced cold allodynia and heat hyperalgesia in the hind paw. 6) The induction of hind paw cold allodynia was different from our study, but it seems to be associated with the difference of mice strain or experimental protocol (C57BL/6 male mice vs. Swiss albino male mice, and acetone solution test vs. cold plate test).…”

“…5) In mice, a single injection of NTG induces acute mechanical, cold, and thermal hypersensitivity, which persists up to four hours post-injection. 3,6) Recently Pradhan et al reported that repetitive injections of NTG induced chronic mechanical hypersensitivity, mimicking the chronic migraines observed in human patients. 7) Since mechanical and thermal hyperalgesia are indicators of migraine-related sensory abnormalities, 7,8) a rodent model of NTG-evoked hypersensitivity is useful for investigating the mechanisms involved in the development of these abnormalities.…”

“…Most patients with migraines experience increased cutaneous sensitivity to non-noxious mechanical, cold, and thermal stimulation of the skin of the cephalic or non-cephalic regions of the body. 2) While central sensitization could contribute to the mechanisms underlying this cutaneous hypersensitivity, 2,3) the exact mechanisms are poorly understood.…”

Modulatory effect of synthetic kynurenic acid derivatives on the nitroglycerin-induced trigeminal activation and sensitization in rats

“…A dose-dependent and prolonged NTG-induced thermal and mechanical allodynia was detected in mice, which were alleviated by sumatriptan (Bates et al, 2010). NTG caused a hyperalgesic response in the tail-flick test, which was attenuated by pre-or co-treatment with non-peptide CGRP receptor antagonist MK-8825 (Greco et al, 2013), inhibition of which receptor is effective in migraine too (Olesen et al, 2004).…”

Role of pituitary adenylate cyclase-activating polypeptide (pacap) in the trigeminovascular system: preclinical and clinical results

“…c-fos, CGRP [98,136], nNOS-immunoreactivity in the NTG model [89], and c-fos [137], nNOS [111], CGRP alterations [110] following the ES of the TRG.…”