Cited by 276Pain Mechanisms and TreatmentsCannabis and Cannabinoid ResearchIon Channels and Receptors

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The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain

Staton, Penny C., Hatcher, Jon P., Walker, Deborah J., Morrison, Alastair D., Shapland, Ellen M., Hughes, Jane P., Chong, Elizabeth, Mander, Palwinder K., Green, Paula J., Billinton, Andy, Fulleylove, Michael, Lancaster, Hilary C., Smith, Jason C., Bailey, Leigh T., Wise, Alan, Brown, Andrew J., Richardson, Jill C., Chessell, Iain P.·2008·Pain

DOI 10.1016/j.pain.2008.04.006

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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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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.
ORCID: Morrison, Alastair D.
Smith, Jason C.
Brown, Andrew J.
Richardson, Jill C.
Venue: Pain
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2008-09-30
Volume: 139
Issue: 1
Pages: 225-236
ISSN: 0304-3959 (ISSN-L)
DOI: 10.1016/j.pain.2008.04.006
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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The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain

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