Activation of Spinal μ- and δ-Opioid Receptors Potently Inhibits Substance P Release Induced by Peripheral Noxious Stimuli

摘要: Over the past few years, δ-opioid receptors (DOPRs) and μ-opioid (MOPRs) have been shown to interact with each other. We previously seen that expression of MOPR is essential for morphine inflammation potentiate analgesic properties selective DOPR agonists. In vivo, it not clear whether MOPRs DOPRs are expressed in same neurons. Indeed, was recently proposed these segregated different populations nociceptors, by peptidergic nonpeptidergic fibers, respectively. present study, role effects DOPR- MOPR-selective agonists two pain models were compared. Using preprotachykinin A knock-out mice, we first confirmed substance P partly mediates intraplantar formalin- capsaicin-induced behaviors. These mice had a significant reduction behavior compared wild-type mice. then measured intrathecal deltorphin II (DOPR agonist) DAMGO (MOPR on pain-like behavior, neuronal activation, release following formalin capsaicin injection. found both able decrease pain, an effect correlated number c-fos-positive neurons superficial laminae lumbar spinal cord. Finally, visualization NK1 (neurokinin 1) receptor internalization revealed activation strongly reduced via direct action primary afferent fibers. Together, our results indicate functional nociceptors.