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The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain
Abstract
It has been postulated that the G protein-coupled receptor, GPR55, is a third cannabinoid receptor. Given that the ligands at the CB(1) and CB(2) receptors are effective analgesic and anti-inflammatory agents, the role of GPR55 in hyperalgesia associated with inflammatory and neuropathic pain has been investigated. As there are no well-validated GPR55 tool compounds, a GPR55 knockout (GPR55(-/-)) mouse line was generated and fully backcrossed onto the C57BL/6 strain. General phenotypic analysis of GPR55(-/-) mice revealed no obvious primary differences, compared with wild-type (GPR55(+/+)) littermates. GPR55(-/-) mice were then tested in the models of adjuvant-induced inflammation and partial nerve ligation. Following intraplantar administration of Freund's complete adjuvant (FCA), inflammatory mechanical hyperalgesia was completely absent in GPR55(-/-) mice up to 14 days post-injection. Cytokine profiling experiments showed that at 14 days post-FCA injection there were increased levels of IL-4, IL-10, IFN gamma and GM-CSF in paws from the FCA-injected GPR55(-/-) mice when compared with the FCA-injected GPR55(+/+) mice. This suggests that GPR55 signalling can influence the regulation of certain cytokines and this may contribute to the lack of inflammatory mechanical hyperalgesia in the GPR55(-/-) mice. In the model of neuropathic hypersensitivity, GPR55(-/-) mice also failed to develop mechanical hyperalgesia up to 28 days post-ligation. These data clearly suggest that the manipulation of GPR55 may have therapeutic potential in the treatment of both inflammatory and neuropathic pain.
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“Deletion of a putative novel cannabinoid receptor, GPR55, is also associated with the failure to develop mechanical hyperalgesia following partial sciatic nerve ligation.72”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [72]
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Metadata
- Authors
- Staton, P. C., Hatcher, J. P., Walker, D. J., Morrison, A. D., Shapland, E. M., Hughes, J. P., Chong, E., Mander, P. K., Green, P. J., Billinton, A., Fulleylove, M., Lancaster, H. C., Smith, J. C., Bailey, L. T., Wise, A., Brown, A. J., Richardson, J. C., & Chessell, I. P.
- Affiliations
- GlaxoSmithKline (United Kingdom) (GB)
- King's College London (GB)
- Corresponding author
- Staton, Penny C.
- Venue
- Pain
- Published
- 2008-09-30
- Volume
- 139
- Issue
- 1
- Pages
- 225-236
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2015263236
- Cited by
- 270
- References
- 49
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 14 · 2023: 12 · 2022: 15 · 2021: 21 · 2020: 18 · 2019: 10 · 2018: 9 · 2017: 20 · 2016: 15 · 2015: 16 · 2014: 10 · 2013: 14 · 2012: 23
- FWCI
- 13.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- GPR55, cannabinoid receptors, mechanical hyperalgesia, inflammatory pain, neuropathic pain, adjuvant-induced inflammation, cytokine expression, analgesia
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Female, Hyperalgesia, Inflammation, Ligation, Male, Mice, Inbred C57BL, Molecular Sequence Data, Neuralgia, Pain Measurement, Physical Stimulation, Mice, Knockout, Inflammation Mediators, Receptors, Cannabinoid, Mice
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