Targeting the EP₃ receptor to combat pain

Although the receptors of prostaglandin E2 (EP₁–EP₄) are considered mediators of pronociceptive signalling, this study showed that the EP₃ receptor can mediate antinociceptive effects. In rats, administration of an EP₃ receptor agonist induced analgesia and reduced responses of nociceptive neurons, but only when the joint was inflamed. Moreover, the EP₃ receptor was expressed in the peripheral nerves of afflicted joints in patients with painful osteoarthritis. The authors suggest that the EP₃ receptor provides endogenous pain control and that agonists of this receptor may be a novel approach to inhibit inflammatory pain.