Inhibition of pain responses by activation of CB 2 cannabinoid receptors

Abstract

Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive evidence demonstrates that CB 1 cannabinoid receptor activation inhibits pain responses. Recently, the synthesis of CB 2 cannabinoid receptor-selective agonists has allowed testing whether CB 2 receptor activation inhibits pain. CB 2 receptor activation is sufficient to inhibit acute nociception, inflammatory hyperalgesia, and the allodynia and hyperalgesia produced in a neuropathic pain model. Studies using site-specific administration of agonist and antagonist have suggested that CB 2 receptor agonists inhibit pain responses by acting at peripheral sites. CB 2 receptor activation also inhibits edema and plasma extravasation produced by inflammation. CB 2 receptor-selective agonists do not produce central nervous system (CNS) effects typical of cannabinoids retaining agonist activity at the CB 1 receptor. Peripheral antinociception without CNS effects is consistent with the peripheral distribution of CB 2 receptors. CB 2 receptor agonists may have promise for the treatment of pain and inflammation without CNS side effects.