AM404, an anandamide transport inhibitor, reduces plasma extravasation in a model of neuropathic pain in rat: role for cannabinoid receptors
Open accessAbstract
Neuropathic pain consequent to peripheral nerve injury has been associated with local inflammation. Following noxious stimulation afferent fibres release substance P (SP) and calcitonin-gene related peptide (CGRP), which are closely related to oedema formation and plasma leakage. The effect of the anandamide transport blocker AM404 has been studied on plasma extravasation after chronic constriction injury (CCI) which consists in a unilateral loose ligation of the rat sciatic nerve (Bennett and Xie, 1988). AM404 (1-3-10 mg kg(-1)) reduced plasma extravasation in the legated paw, measured as mug of Evans Blue per gram of fresh tissue. A strong effect on vascular permeability was also produced by the synthetic cannabinoid agonist WIN 55,212-2 (0.1-0.3-1 mg kg(-1)). Using specific antagonists or enzyme inhibitors, we demonstrate that cannabinoids act at several levels: data on the 3rd day suggest a strong involvement of substance P (SP) and calcitonin gene-related peptide (CGRP) in the control of vascular tone, whereas at the 7th and 14th days the major role seems to be played by prostaglandins (PGs) and nitric oxide (NO). Capsaicin injection in ligated paws of AM404- or WIN 55,212-2-treated rats resulted in an increase of Evans Blue extravasation, suggesting the involvement of the cannabinergic system in the protective effect of C fibres of ligated paws. Taken together, these data demonstrate the efficacy of cannabinoids in controlling pain behaviour through the modulation of several pain mediators and markers of vascular reactivity, such as SP, CGRP, PGs and NO.
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In CCI rats, chronic administration of either AM404 or URB597 suppresses plasma extravasation, a condition associated with neuropeptide release at peripheral levels.
“In CCI rats, chronic administration of either AM404 or URB597 suppresses plasma extravasation, a condition associated with neuropeptide release at peripheral levels.54, 55”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [54]
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- Authors
- La Rana, G., Russo, R., D'Agostino, G., Sasso, O., Raso, G. M., Iacono, A., Meli, R., Piomelli, D., & Calignano, A.
- Affiliations
- University of Naples Federico II (IT)
- University of California, Irvine (US)
- Corresponding author
- Calignano, A.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 54
- Issue
- 3
- Pages
- 521-529
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2144642698
- Cited by
- 42
- References
- 40
- Citations by year
- 2023: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 5 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 5
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Sanofi
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- AM404, neuropathic pain, chronic constriction injury, plasma extravasation, vascular permeability, cannabinoid receptors, WIN 55,212-2, substance P, calcitonin gene-related peptide, prostaglandins, nitric oxide, capsaicin, C-fibers, peripheral nerve injury, edema
- MeSH terms
- Analgesics, Analysis of Variance, Animals, Arachidonic Acids, Capillary Permeability, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme Inhibitors, Evans Blue, Hyperalgesia, Male, Morpholines, Motor Activity, Naphthalenes, Pain Measurement, Plasma, Reaction Time, Sciatica, Rats, Wistar, Pain Threshold, Receptors, Cannabinoid, Benzoxazines, Rats
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