Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine
Autor: | G. Nappi, Tiziano Bandiera, Rosaria Greco, Giorgio Sandrini, Antonina Stefania Mangione, Francesca Siani, Cristina Tassorelli, Chiara Demartini, Andrea Armirotti, A Guijarro, Daniele Piomelli |
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Rok vydání: | 2015 |
Předmět: |
Male
Pharmacology Amidohydrolases Rats Sprague-Dawley Nitroglycerin chemistry.chemical_compound Fatty acid amide hydrolase medicine Animals Analgesics Dose-Response Relationship Drug Cannabinoids business.industry Pain Perception General Medicine Anandamide medicine.disease Endocannabinoid system Rats Disease Models Animal Treatment Outcome Nociception Migraine chemistry Hyperalgesia Anesthesia Locus coeruleus Neurology (clinical) medicine.symptom business Tail flick test |
Zdroj: | Cephalalgia. 35:1065-1076 |
ISSN: | 1468-2982 0333-1024 |
Popis: | Background Systemic nitroglycerin (NTG) activates brain nuclei involved in nociceptive transmission as well as in neuroendocrine and autonomic functions in rats. These changes are considered relevant for migraine because NTG consistently provokes spontaneous-like migraine attacks in migraineurs. Several studies have suggested a relationship between the endocannabinoid levels and pain mediation in migraine. URB937, a peripheral inhibitor of fatty acid amide hydrolase (FAAH)—the enzyme that degrades anandamide, produces analgesia in animal models of pain, but there is no information on its effects in migraine. Aim We evaluated whether URB937 alters nociceptive responses in the animal model of migraine based on NTG administration in male rats, using the tail flick test and the plantar and orofacial formalin tests, under baseline conditions and after NTG administration. Furthermore, we investigated whether URB937 affects NTG-induced c-Fos expression in the brain. Results During the tail flick test, URB937 showed an antinociceptive effect in baseline conditions and it blocked NTG-induced hyperalgesia. URB937 also proved effective in counteracting NTG-induced hyperalgesia during both the plantar and orofacial formalin tests. Mapping of brain nuclei activated by NTG indicates that URB937 significantly reduces c-Fos expression in the nucleus trigeminalis caudalis and the locus coeruleus. Conclusions The data suggest that URB937 is capable of changing, probably via indirect mechanisms, the functional status of central structures that are important for pain transmission in an animal model of migraine. |
Databáze: | OpenAIRE |
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