The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat
Abstract
Our study addressed the hypothesis that spinal release of endogenous opioids underlies Delta9-tetrahydrocannabinol (Delta9-THC)-induced antinociception in Freund's adjuvant-induced arthritic and nonarthritic rats. The paw-pressure test was used to assess the antinociceptive effects of Delta9-THC versus those of morphine, and opioid and cannabinoid receptor-selective antagonists were used to characterize the involved receptors. Cerebrospinal fluid was collected after Delta9-THC injection (i.p.) for the measurement of endogenous opioid peptides. Our results indicate that morphine or Delta9-THC is equally potent and efficacious in both nonarthritic and arthritic rats. Delta9-THC-induced antinociception is attenuated by the kappa opioid receptor antagonist, nor-binaltorphimine, in arthritic rats only. Delta9-THC induces increased immunoreactive dynorphin A (idyn A) levels in nonarthritic rats while decreasing idyn A in arthritic rats. We hypothesize that the elevated idyn A level in arthritic rats contributes to hyperalgesia by interaction with N-methyl-D-aspartate receptors, and that Delta9-THC induces antinociception by decreasing idyn A release.
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Naloxone blocks the antinociceptive effects of THC in both arthritic and nonarthritic rats.
“For example, naloxone blocks the antinociceptive effects of THC in both arthritic and nonarthritic rats (Cox and Welch, 2004;Smith et al, 1998).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Cox and Welch, 2004
THC attenuates spinal dynorphin levels in arthritic rats.
“Furthermore, THC attenuates spinal dynorphin levels in arthritic rats, indicating interactions between the opioid and endocannabinoid systems (Cox and Welch, 2004).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Cox and Welch, 2004
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Self-citation
- Authors
- Cox, M. L., & Welch, S. P.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Welch, Sandra P
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 493
- Issue
- 1-3
- Pages
- 65-74
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2035976555
- Cited by
- 35
- References
- 39
- Citations by year
- 2025: 1 · 2024: 3 · 2022: 2 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 3 · 2015: 2 · 2013: 2
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k02da000186-09)
- National Institute on Drug Abuse (DA 07027, DA 05274, K02 DA-00186, T32DA007027)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- delta-9-tetrahydrocannabinol, antinociception, adjuvant-induced arthritis, endogenous opioids, kappa opioid receptor, nor-binaltorphimine, dynorphin A, NMDA receptor, hyperalgesia, morphine, cerebrospinal fluid
- MeSH terms
- Rimonabant, Animals, Arthritis, Experimental, Dose-Response Relationship, Drug, Dynorphins, Enkephalin, Leucine, Enkephalin, Methionine, Freund's Adjuvant, Injections, Intradermal, Injections, Intraperitoneal, Male, Morphine, Mycobacterium, Naloxone, Naltrexone, Narcotic Antagonists, Pain, Pain Measurement, Piperidines, Pyrazoles, Receptors, Opioid, Dronabinol, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB1, Rats, Cannabinoid Receptor Antagonists
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