Targeting cannabinoid agonists for inflammatory and neuropathic pain

Abstract

The cannabinoid receptors CB₁ and CB₂ are class A G-protein-coupled receptors. It is well known that cannabinoid receptor agonists produce relief of pain in a variety of animal models by interacting with cannabinoid receptors. CB₁ receptors are located centrally and peripherally, whereas CB₂ receptors are expressed primarily on immune cells and tissues. A large body of preclinical data supports the hypothesis that either CB₂-selective agonists or CB₁ agonists acting at peripheral sites, or with limited CNS exposure, will inhibit pain and neuroinflammation without side effects within the CNS. There has been a growing interest in developing cannabinoid agonists. Many new cannabinoid ligands have been synthesized and studied covering a wide variety of novel structural scaffolds. This review focuses on the present development of cannabinoid agonists with an emphasis on selective CB₂ agonists and peripherally restricted CB₁ or CB₁/CB₂ dual agonists for treatment of inflammatory and neuropathic pain.

Keywords::

• cannabinoid
• CB₁ receptor
• CB₂ receptor
• inflammatory pain
• neuropathic pain

Acknowledgements

This paper is dedicated to CA Willoughby.

Notes