Can supraspinal δ-opioid receptors mediate antinociception?

The antinociception mediated by supraspinal opioid receptors has traditionally been thought to arise solely from activation of the μ-opioid receptor subtype. There is a growing body of evidence, however, which suggests that supraspinal δ-opioid receptors may also be able to directly initiate antinociception. Frank Porreca and colleagues review the evidence favoring exclusive involvement of μ-opioid receptors (as well as studies implicating δ-opioid receptors) in supraspinal antinociceptors. They conclude that δ-opioid receptors can be pharmacologically activated to initiate antinociception, suggesting the existence of an alternative mechanism for pain relief which may be of significant clinical importance.