Analgesic and antiinflammatory effects of cannabinoid receptor agonists in a rat model of neuropathic pain
Abstract
Cannabinoid receptor (CB) agonists are known to attenuate allodynia in a range of pain models, but their long-term effects and their mechanisms of action are controversial. The present study compares the antiallodynic effects of long-term treatment with a mixed CB1/CB2 (WIN55,212-2) and a selective CB2 (GW405833) cannabinoid receptor agonist and correlates these effects with their influences on spinal cord (SC) glial activation. The substances were applied daily in a rat neuropathic pain model. Tactile allodynia was assessed, and the development of gliosis was illustrated with immunohistochemical methods. Both substances reduced mechanical allodynia. Their analgesic effect was accompanied by a significant reduction in reactive gliosis and cathepsins (CAT) X and S expression. A daily injection of either substance for 8 days was sufficient to induce a sustained antiallodynic effect, which persisted up to 6 days after the last injection. The re-appearance of mechanical allodynia after this period was associated with a breakout of a strong gliotic response in the lumbar SC. Our results emphasize the therapeutic efficacy of cannabinoid receptor agonists and their inhibitory effects on the formation of gliosis.
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Chronic administration of WIN55,212-2 produced anti-allodynic effects up to six days following the final injection.
“Chronic administration of WIN55,212-2 produced anti-allodynic effects up to six days following the final injection.”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [81]
Chronic administration of WIN55,212-2 attenuates the development of mechanical allodynia and suppresses glial activation in the spinal cord following SNL with no overt motor side-effects.
“Chronic administration of WIN55,212-2 also attenuates the development of mechanical allodynia and suppresses glial activation in the spinal cord following SNL with no overt motor side-effects.81”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [81]
GW405833 administered chronically suppressed the development of mechanical allodynia concomitant with suppression of glial activation at the level of the spinal cord.
“The CB2-specific agonist GW405833, administered chronically, suppressed the development of mechanical allodynia concomitant with suppression of glial activation at the level of the spinal cord.81”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [81]
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References 57 · Cited by 39
- Authors
- Leichsenring, A., Andriske, M., Bäcker, I., Stichel, C. C., & Lübbert, H.
- Affiliations
- Ruhr University Bochum (DE)
- Biofrontera (Germany) (DE)
- Corresponding author
- Stichel, Christine C.
- Venue
- Naunyn-Schmiedeberg s Archives of Pharmacology
- Published
- 2009-01-18
- Volume
- 379
- Issue
- 6
- Pages
- 627-636
- ISSN
- 0028-1298 (ISSN-L)
- 1432-1912
- OpenAlex
- W1990110686
- Cited by
- 39
- References
- 57
- Citations by year
- 2024: 3 · 2023: 4 · 2021: 1 · 2020: 2 · 2019: 2 · 2017: 5 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Naunyn-Schmiedeberg s Archives of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- cannabinoid receptor agonists, neuropathic pain, allodynia, WIN 55,212-2, CB2 receptor, reactive gliosis, cathepsin X, cathepsin S, long-term analgesia, mechanical allodynia
- MeSH terms
- Analgesics, Animals, Anti-Inflammatory Agents, Non-Steroidal, Cannabinoids, Disease Models, Animal, Indoles, Male, Morpholines, Naphthalenes, Neuralgia, Pain, Rats, Wistar, Receptors, Cannabinoid, Benzoxazines, Rats, Cannabinoid Receptor Agonists
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