Abstract | BACKGROUND: Reactive nitroxidative species, such as nitric oxide but particularly peroxynitrite, have been strongly implicated in pain mechanisms. Targeting peroxynitrite is anti-nociceptive in pain models, but little is known about its role in migraine mechanisms. Given the need to validate novel targets for migraine headache, our objective was to study the potential of reactive nitroxidative species, particularly peroxynitrite, as novel targets for drug discovery and their role in migraine mechanisms. METHODS: We recorded neuronal activity in rats with extracellular electrodes and examined the effects of targeting nitric oxide or peroxynitrite on ongoing and cranial-evoked firing rates of central trigeminocervical neurons. We injected calcitonin gene-related peptide (which produces migraine-like headache in migraineurs) and characterized neuronal responses to cranial stimulation and on behavioral responses to nociceptive periorbital stimulation and determined the effects of targeting reactive nitroxidative species on the mediated changes. RESULTS:
L-NAME ( nitric oxide synthase inhibitor) and Fe(III)5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato chloride (FeTPPS; peroxynitrite decomposition catalyst) inhibited ongoing and dural-evoked responses of trigeminocervical neurons, without affecting normal facial-cutaneous responses. Calcitonin gene-related peptide caused activation and sensitization of dural-responsive trigeminovascular neurons with hypersensitivity to intracranial and extracranial stimulation, and reduction of periorbital withdrawal thresholds. Only the peroxynitrite decomposition catalyst prevented these neuronal and behavioral nociceptive responses. DISCUSSION:
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Authors | Simon Akerman, Daniela Salvemini, Marcela Romero-Reyes |
Journal | Cephalalgia : an international journal of headache
(Cephalalgia)
Vol. 41
Issue 11-12
Pg. 1187-1200
(10 2021)
ISSN: 1468-2982 [Electronic] England |
PMID | 34256650
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Nitric Oxide
- Calcitonin Gene-Related Peptide
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Topics |
- Animals
- Calcitonin Gene-Related Peptide
- Headache
- Migraine Disorders
(drug therapy)
- Neurons
- Nitric Oxide
- Rats
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