The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain
Abstract
We have examined the effects of cannabinoid agonists on hyperalgesia in a model of neuropathic pain in the rat and investigated the possible sites of action. The antihyperalgesic activity of the cannabinoids was compared with their ability to elicit behavioural effects characteristic of central cannabinoid activity. WIN55,212-2 (0.3-10 mg kg(-1)), CP-55,940 (0.03-1 mg kg(-1)) and HU-210 (0.001-0.03 mg kg(-1)) were all active in a 'tetrad' of tests consisting of tail-flick, catalepsy, rotarod and hypothermia following subcutaneous administration, with a rank order of potency in each of HU-210 > CP-55,940 > WIN55,212-2. The effects of WIN55,212-2 in each assay were blocked by the Cannabinoid1 (CB1) antagonist SR141716A. In the partial sciatic ligation model of neuropathic pain WIN55,212-2, CP-55,940 and HU-210 produced complete reversal of mechanical hyperalgesia within 3 h of subcutaneous administration with D50 values of 0.52, 0.08 and 0.005 mg kg(-1), respectively. In this model WIN55,212-2 was also effective against thermal hyperalgesia and mechanical allodynia. WIN55,212-2 produced pronounced reversal of mechanical hyperalgesia following intrathecal administration that was blocked by the CB1 antagonist SR141716A. Following intraplantar administration into the ipsilateral hindpaw, WIN55,212-2 produced up to 70% reversal of mechanical hyperalgesia, although activity was also observed at high doses following injection into the contralateral paw. The antihyperalgesic effect of WIN55,212-2 injected into the ipsilateral paw was blocked by subcutaneously administered SR141716A, but was not affected by intrathecally administered SR141716A. These data show that cannabinoids are highly potent and efficacious antihyperalgesic agents in a model of neuropathic pain. This activity is likely to be mediated via an action in both the CNS and in the periphery.
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Several studies report efficacy of mixed cannabinoid CB1/CB2 agonists in the Seltzer model, although CNS side-effects were observed in the same dose range that resulted in full reversal of neuropathic nociception.
“Several studies report efficacy of mixed cannabinoid CB1/CB2 agonists in this model, although CNS side-effects were nonetheless observed in the same dose range that resulted in full reversal of neuropathic nociception.68”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [68]
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- Authors
- Fox, A., Kesingland, A., Gentry, C., McNair, K., Patel, S., Urban, L., & James, I.
- Affiliations
- Novartis (Switzerland) (CH)
- Corresponding author
- Fox, Alyson
- Venue
- Pain
- Published
- 2001-05
- Volume
- 92
- Issue
- 1
- Pages
- 91-100
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W1968426375
- Cited by
- 379
- References
- 35
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 8 · 2023: 7 · 2022: 5 · 2021: 11 · 2020: 9 · 2019: 13 · 2018: 11 · 2017: 10 · 2016: 9 · 2015: 8 · 2014: 8 · 2013: 15 · 2012: 22
- FWCI
- 13.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (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 Opioid Use
- Keywords
- cannabinoid 1 receptor, CB1 receptor, neuropathic pain, antihyperalgesia, WIN 55,212-2, CP55,940, HU-210, SR141716A, mechanical hyperalgesia, thermal hyperalgesia, mechanical allodynia, intrathecal administration, intraplantar administration
- MeSH terms
- Rimonabant, Analgesics, Animals, Cannabinoids, Cyclohexanols, Disease Models, Animal, Hyperalgesia, Morpholines, Naphthalenes, Pain Measurement, Piperidines, Pyrazoles, Receptors, Drug, Sciatica, Dronabinol, Rats, Wistar, Receptors, Cannabinoid, Benzoxazines, Rats
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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