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The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain
Abstract
Cannabidiol, the major psycho-inactive component of cannabis, has substantial anti-inflammatory and immunomodulatory effects. This study investigated its therapeutic potential on neuropathic (sciatic nerve chronic constriction) and inflammatory pain (complete Freund's adjuvant intraplantar injection) in rats. In both models, daily oral treatment with cannabidiol (2.5-20 mg/kg to neuropathic and 20 mg/kg to adjuvant-injected rats) from day 7 to day 14 after the injury, or intraplantar injection, reduced hyperalgesia to thermal and mechanical stimuli. In the neuropathic animals, the anti-hyperalgesic effect of cannabidiol (20 mg/kg) was prevented by the vanilloid antagonist capsazepine (10 mg/kg, i.p.), but not by cannabinoid receptor antagonists. Cannabidiol's activity was associated with a reduction in the content of several mediators, such as prostaglandin E(2) (PGE(2)), lipid peroxide and nitric oxide (NO), and in the over-activity of glutathione-related enzymes. Cannabidiol only reduced the over-expression of constitutive endothelial NO synthase (NOS), without significantly affecting the inducible form (iNOS) in inflamed paw tissues. Cannabidiol had no effect on neuronal and iNOS isoforms in injured sciatic nerve. The compound's efficacy on neuropathic pain was not accompanied by any reduction in nuclear factor-kappaB (NF-kappaB) activation and tumor necrosis factor alpha (TNFalpha) content. The results indicate a potential for therapeutic use of cannabidiol in chronic painful states.
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“However, anti-hyperalgesic effects observed with these compounds are likely to be independent of cannabinoid receptors, and may be mediated through TRPV1.”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [40]
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Metadata
- Authors
- Costa, B., Trovato, A. E., Comelli, F., Giagnoni, G., & Colleoni, M.
- Affiliations
- University of Milano-Bicocca (IT)
- University of Milan (IT)
- Corresponding author
- Costa, Barbara
- ORCID
- Costa, Barbara
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 556
- Issue
- 1-3
- Pages
- 75-83
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W1967303451
- Cited by
- 395
- References
- 46
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 37 · 2023: 42 · 2022: 37 · 2021: 43 · 2020: 35 · 2019: 20 · 2018: 17 · 2017: 16 · 2016: 14 · 2015: 8 · 2014: 9 · 2013: 11 · 2012: 14
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Keywords
- cannabidiol, neuropathic pain, inflammatory pain, chronic constriction injury, complete Freund's adjuvant, hyperalgesia, capsazepine, vanilloid receptor, prostaglandin E2, nitric oxide, endothelial nitric oxide synthase, glutathione, NF-κB, TNF-α, anti-inflammatory activity, oral administration
- MeSH terms
- Administration, Oral, Animals, Cannabidiol, Cannabis, Capsaicin, Chronic Disease, Freund's Adjuvant, Hyperalgesia, Inflammation, Lipid Peroxides, Male, Nitric Oxide, Pain, Pain Measurement, Tumor Necrosis Factor-alpha, Dinoprostone, NF-kappa B, Rats, Wistar, Nitric Oxide Synthase, Sciatic Neuropathy, Rats, Cannabinoid Receptor Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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