Targeting cannabinoid agonists for inflammatory and neuropathic pain

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. CB, 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 CB, 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.