The delta opioid receptor and brain pain-modulating circuits

Although it has long been recognized that the prototypic opioid analgesic morphine acts in the central nervous system to produce analgesia, the underlying mechanisms have only recently been elucidated at the level of neural circuits. Mu opioid receptors have received the most attention. Multiple lines of evidence now demonstrate that the basis for the analgesic actions of drugs acting at themuopioid receptor is recruitment of a brainstempainmodulatory network that includes the midbrain periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) [1,2]. The role of the kappa receptor in supraspinal mechanisms of pain modulation is also reasonably well understood. However, contrary to general expectations regarding the effects of opioids, activation of kappa receptors in brainstem pain modulatory circuits often exerts a functional antagonism of supraspinal mu opioid analgesia [3]. By comparison, analysis of the role of supraspinal delta receptors in pain mod-ulation is less developed. This review will consider the evidence relating to the function of the delta receptor in brainstem pain modulatory circuitry.