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PMID: 9539680 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors.

Pain ·Vol. 75 ·No. 1 ·1998-03-00 ·Pages 111-119

Richardson JD, Kilo S, Hargreaves KM

Abstract

Central antinociceptive effects of cannabinoids have been well documented. However, relatively little is known about the peripheral effects of the cannabinoids on inflammation. In the present study, we evaluated the effects of peripherally administered cannabinoids on three indices of inflammation: carrageenan-induced thermal hyperalgesia, carrageenan-induced edema, and capsaicin-induced plasma extravasation. In addition, we determined the effect of cannabinoids on capsaicin-evoked neuropeptide release from isolated rat hindpaw skin. Our results indicate that cannabinoids produce antihyperalgesia via interaction with a peripheral CB1 receptor. Peripheral, but not systemic, administration of 0.01 ng anandamide inhibited the induction of hyperalgesia. Peripheral administration of anandamide also attenuated hyperalgesia after its development via interaction with the CB1 cannabinoid receptor subtype as indicated by its reversal with the CB1 receptor antagonist SR 141716A. Additionally, peripheral, but not systemic, administration of 0.01 ng anandamide inhibited edema. Peripherally administered cannabinoids also interacted with CB1 receptors to inhibit capsaicin-evoked plasma extravasation into the hindpaw. One potential mechanism for the anti-inflammatory actions of the cannabinoids is the inhibition of neurosecretion from the peripheral terminals of nociceptive primary afferent fibers. This hypothesis is supported by the finding that anandamide inhibited capsaicin-evoked release of calcitonin gene-related peptide from isolated hindpaw skin. Collectively, these results indicate that cannabinoids reduce inflammation via interaction with a peripheral CB1 receptor. A potential mechanism for this effect is the inhibition of neurosecretion from capsaicin-sensitive primary afferent fibers.

MeSH Terms
Animals Anti-Inflammatory Agents/pharmacology Arachidonic Acids/pharmacology Calcitonin Gene-Related Peptide/metabolism Capillary Permeability/drug effects Capsaicin/pharmacology Carrageenan Edema/chemically induced,prevention & control Endocannabinoids Hindlimb/blood supply Hyperalgesia/chemically induced,physiopathology,prevention & control Male Polyunsaturated Alkamides Rats Rats, Sprague-Dawley Receptors, Cannabinoid Receptors, Drug/drug effects,physiology Skin/drug effects,metabolism
Chemicals
Anti-Inflammatory Agents Arachidonic Acids Endocannabinoids Polyunsaturated Alkamides Receptors, Cannabinoid Receptors, Drug methanandamide Carrageenan Calcitonin Gene-Related Peptide Capsaicin anandamide
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Richardson Jennelle Durnett
Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA Department of Restorative Sciences, University of Minnesota, Minneapolis, MN 55455, USA.
Kilo Sonja
Hargreaves Kenneth M
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Article Info
Journal
Pain
Abbr.
Pain
ISSN
0304-3959
DOI
10.1016/S0304-3959(97)00213-3
Published
1998-03-00
Pages
111-119
Language
English
Region
United States
NLM ID
7508686
Subset
IM
Grants
NIDCR NIH HHS · DE9860 · United States
External Links
PubMed source DOI: 10.1016/S0304-3959(97)00213-3 View journal details
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