The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Ethical guidelines for investigations of experimental pain in conscious animals.
Zimmermann, M. (1983) · Pain · doi:10.1016/0304-3959(83)90201-4 · Cited by 7,762
A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man
Bennett, G. J., & Xie, Y.-K. (1988) · Pain · doi:10.1016/0304-3959(88)90209-6 · Cited by 5,376
Wendel, A. (1981) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(81)77046-0 · Cited by 3,032
Pharmacology of cannabinoid CB1 and CB2 receptors
Pertwee, R. G. (1997) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(97)82001-3 · Cited by 1,526
Bisogno, T., Hanuš, L., PETROCELLIS, L. D., Tchilibon, S., Ponde, D. E., Brandi, I., Moriello, A. S., Davis, J. B., Mechoulam, R., & Marzo, V. D. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704327 · Cited by 1,315
Cannabidiol and (−)Δ 9 -tetrahydrocannabinol are neuroprotective antioxidants
Hampson, A. J., Grimaldi, M., Axelrod, J., & Wink, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.8268 · Cited by 850
Subbaramaiah, K., Chung, W. J., Michaluart, P., TELANG, N. T., Tanabe, T., Inoue, H., Jang, M., Pezzuto, J. M., & Dannenberg, A. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.34.21875 · Cited by 786
SR 144528, the First Potent and Selective Antagonist of the CB2 Cannabinoid Receptor
Rinaldi, M. L., Barth, F., Millan, J., Derocq, J., Casellas, P., Congy, C., Oustric, D., Sarran, M., Bouaboula, M., Calandra, B., et al. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37266-0 · Cited by 716
Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis
Rog, D. J., Nurmikko, T. J., Friede, T., & Young, C. A. (2005) · Neurology · doi:10.1212/01.wnl.0000176753.45410.8b · Cited by 679
Malfait, A. M., Gallily, R., Sumariwalla, P. F., Malik, A. S., Andreakos, E., Mechoulam, R., & Feldmann, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.160105897 · Cited by 669
Russo, E. B., & Guy, G. W. (2005) · Medical Hypotheses · doi:10.1016/j.mehy.2005.08.026 · Cited by 608
Blake, D. R., Robson, P., Ho, M., Jubb, R. W., & McCabe, C. S. (2006) · Rheumatology · doi:10.1093/rheumatology/kei183 · Cited by 433
Iuvone, T., Esposito, G., Esposito, R., Santamaria, R., Di Rosa, M., & Izzo, A. A. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2003.02327.x · Cited by 361
Cannabinoids and neuroinflammation
Walter, L. M., & Stella, N. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705667 · Cited by 341
Costa, B., Giagnoni, G., Franke, C., Trovato, A. E., & Colleoni, M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705920 · Cited by 291
Hyperalgesia in experimental neuropathy is dependent on the TNF receptor 1
Sommer, C., Schmidt, C., & George, A. (1998) · Experimental Neurology · doi:10.1006/exnr.1998.6797 · Cited by 291
Costa, B., Colleoni, M., Conti, S., Parolaro, D., Franke, C., Trovato, A. E., & Giagnoni, G. (2004) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-004-0871-3 · Cited by 243
Nitric Oxide: A Novel Mediator of Inflammation
Clancy, R. M., & Abramson, S. B. (1995) · Experimental Biology and Medicine · doi:10.3181/00379727-210-43927aa · Cited by 233
Amaya, F., Oh‐hashi, K., Naruse, Y., Iijima, N., Ueda, M., Shimosato, G., Tominaga, M., Tanaka, Y., & Tanaka, M. (2003) · Brain Research · doi:10.1016/s0006-8993(02)03972-0 · Cited by 226
Esposito, G., De Filippis, D., Maiuri, M. C., De Stefano, D., Carnuccio, R., & Iuvone, T. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.01.047 · Cited by 225
Bridges, D., Ahmad, K., & Rice, A. S. C. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704110 · Cited by 222
Naik, A. K., Tandan, S. K., Dudhgaonkar, S. P., Jadhav, S. H., Kataria, M., Prakash, V. R., & Kumar, D. (2005) · European Journal of Pain · doi:10.1016/j.ejpain.2005.08.006 · Cited by 194
VR1, but not P2X3, increases in the spared L4 DRG in rats with L5 spinal nerve ligation
Fukuoka, T., Tokunaga, A., Tachibana, T., Dai, Y., Yamanaka, H., & Noguchi, K. (2002) · Pain · doi:10.1016/s0304-3959(02)00067-2 · Cited by 190
SZALLASI, A., & Blumberg, P. M. (1990) · Life Sciences · doi:10.1016/0024-3205(90)90518-v · Cited by 185
Kanai, Y., Nakazato, E., Fujiuchi, A., Hara, T., & Imai, A. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.05.003 · Cited by 149
Costa, B., Conti, S., Giagnoni, G., & Colleoni, M. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704900 · Cited by 142
Alba, J. D., Clayton, N. M., Collins, S. D., Colthup, P. V., Chessell, I. P., & Knowles, R. G. (2005) · Pain · doi:10.1016/j.pain.2005.10.028 · Cited by 133
Scott, D. A., Wright, C. E., & Angus, J. A. (2004) · Pain · doi:10.1016/j.pain.2004.01.020 · Cited by 129
Hypolocomotor effects in rats of capsaicin and two long chain capsaicin homologues
Marzo, V. D., Lastres‐Becker, I., Bisogno, T., PETROCELLIS, L. D., Milone, A., Davis, J. B., & Fernández‐Ruíz, J. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(01)01012-3 · Cited by 126
Pharmacology of Cannabinoid CB 1 and CB 2 Receptors
Pertwee, R. G. (1997) · Pharmacology & Therapeutics · Cited by 112
Local nitric oxide synthase activity in a model of neuropathic pain
Levy, D., & Zochodne, D. W. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00186.x · Cited by 104
Costa, B., Trovato, A. E., Colleoni, M., Giagnoni, G., Zarini, E., & Croci, T. (2005) · Pain · doi:10.1016/j.pain.2005.03.043 · Cited by 104
Chu, Y., Guan, Y., SKINNER, J. T., Raja, S. N., Johns, R. A., & Tao, Y. (2005) · Pain · doi:10.1016/j.pain.2005.09.024 · Cited by 101
Cyclooxygenase inhibition in nerve-injury- and TNF-induced hyperalgesia in the rat
Schäfers, M., Marziniak, M., Sorkin, L. S., Yaksh, T. L., & Sommer, C. (2003) · Experimental Neurology · doi:10.1016/j.expneurol.2003.09.015 · Cited by 99
The Pharmacology and Therapeutic Potential of Plant Cannabinoids
Cascio, M. G., Pertwee, R. G., & Marini, P. (2017) · Springer eBooks · doi:10.1007/978-3-319-54564-6_9 · Cited by 94
Hecker, M., Preiß, C., Klemm, P. L., & Busse, R. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15660.x · Cited by 88
Finn, D. P., Beckett, S. R. G., Roe, C. H., Madjd, A., Fone, K. C. F., Kendall, D. A., Marsden, C. A., & Chapman, V. (2004) · European Journal of Neuroscience · doi:10.1111/j.0953-816x.2004.03177.x · Cited by 76
SZALLASI, A., Bíró, T., Szabó, T. G., Modarres, S., Petersen, M., Klusch, A., Blumberg, P. M., Krause, J. E., & Sterner, O. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702440 · Cited by 56
Glutathione reductase activity, riboflavin status, and disease activity in rheumatoid arthritis.
Mulherin, D. M., Thurnham, D. I., & Situnayake, R. D. (1996) · Annals of the Rheumatic Diseases · doi:10.1136/ard.55.11.837 · Cited by 50
O’Rielly, D. D., & Loomis, C. W. (2006) · Anesthesiology · doi:10.1097/00000542-200602000-00019 · Cited by 47
MODULATION OF OXIDANT STATUS BY MELOXICAM IN EXPERIMENTALLY INDUCED ARTHRITIS
Agha, A. M., El-Khatib, A. S., & AL-ZUHAIR, H. (1999) · Pharmacological Research · doi:10.1006/phrs.1999.0522 · Cited by 36
Simplicio, P. D., Giorgio, L. A. D., Cardaioli, E., LECIS, R., MICELI, M., Rossi, R., Anichini, R., Mian, M., Seghieri, G., & Franconi, F. (1995) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1995.tb01983.x · Cited by 35
Antinociceptive activity of ricinoleic acid, a capsaicin-like compound devoid of pungent properties
Vieira, C., Evangelista, S., Cirillo, R., Terracciano, R., Lippi, A., Maggi, C. A., & Manzini, S. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00727-5 · Cited by 32
Mononuclear Phagocyte Antimicrobial and Antitumor Activity: the Role of Oxygen Intermediates
Murray, H. W., & Cohn, Z. A. (1980) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12543457 · Cited by 29
[202] Glutathione reductase (Yeast)
Colman, R. F. (1971) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(71)17088-7 · Cited by 19
Modulation of Nitric Oxide Synthesis in Inflammation
Gad, M. Z., & Khattab, M. M. (2011) · Arzneimittelforschung · doi:10.1055/s-0031-1300229 · Cited by 19
Cited by
Sorted by citations
Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.
Russo, E. B. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01238.x · Cited by 1,535
De Petrocellis, L., Ligresti, A., Moriello, A. S., Allarà, M., Bisogno, T., Petrosino, S., Stott, C. G., & Di Marzo, V. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01166.x · Cited by 946
Antioxidative and Anti-Inflammatory Properties of Cannabidiol
Atalay, S., Jarocka-Karpowicz, I., & Skrzydlewska, E. (2019) · Antioxidants · doi:10.3390/antiox9010021 · Cited by 889
Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb
Izzo, A. A., Borrelli, F., Capasso, R., Marzo, V. D., & Mechoulam, R. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.07.006 · Cited by 879
Cannabidiol: State of the art and new challenges for therapeutic applications
Pisanti, S., Malfitano, A. M., Ciaglia, E., Lamberti, A., Ranieri, R., Cuomo, G., Abate, M., Faggiana, G., Proto, M., Fiore, D., et al. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.041 · Cited by 664
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 ›
Are you an author, or do you see a problem with this page? Request a review
