Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine
Open accessAbstract
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.
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The peripherally restricted FAAH inhibitor URB937 administration evoked an anti-hyperalgesic effect in rats.
“Others have found that the peripherally restricted FAAH inhibitor URB937 administration evoked anti-hyperalgesic effect in rats (Greco et al, 2015).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Greco et al, 2015
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Cannabinoids and Endocannabinoids
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Self-citationCannabinoids and Endocannabinoids
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Gel-forming antagonist provides a lasting effect on CGRP-induced vasodilation
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Endocannabinoid Modulation in Headache: Mechanisms, Models, and Translational Therapies
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- Authors
- Greco, R., Bandiera, T., Mangione, A., Demartini, C., Siani, F., Nappi, G., Sandrini, G., Guijarro, A., Armirotti, A., Piomelli, D., & Tassorelli, C.
- Affiliations
- Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IT)
- Italian Institute of Technology (IT)
- Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, C. Mondino National Neurological Institute, Italy
- University of Pavia (IT)
- University of California System (US)
- Corresponding author
- Greco, R
- ORCID
- Venue
- Cephalalgia
- Publisher
- SAGE Publications
- Published
- 2015-01-21
- Volume
- 35
- Issue
- 12
- Pages
- 1065-1076
- ISSN
- 0333-1024 (ISSN-L)
- 1468-2982
- OpenAlex
- W1991879618
- Cited by
- 63
- References
- 43
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 1 · 2023: 2 · 2022: 10 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 5 · 2015: 3
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cephalalgia (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Keywords
- fatty acid amide hydrolase inhibition, nitroglycerin, hyperalgesia, endocannabinoid system, anandamide, antinociception, Fos expression, nucleus caudalis, locus coeruleus, orofacial pain, tail-flick test
- MeSH terms
- Fatty Acid Amide Hydrolases, Amidohydrolases, Analgesics, Animals, Cannabinoids, Disease Models, Animal, Dose-Response Relationship, Drug, Nitroglycerin, Hyperalgesia, Male, Treatment Outcome, Rats, Sprague-Dawley, Rats, Pain Perception
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