Delta opioid receptor analgesia: recent contributions from pharmacology and molecular approaches

Abstract

Delta opioid receptors represent a promising target for the development of novel analgesics. A number of tools have been developed recently that have significantly improved our knowledge of δ receptor function in pain control. These include several novel δ agonists with potent analgesic properties, and genetic mouse models with targeted mutations in the δ opioid receptor gene. Also, recent findings have further documented the regulation of δ receptor function at cellular level, which impacts on the pain-reducing activity of the receptor. These regulatory mechanisms occur at transcriptional and post-translational levels, along agonist-induced receptor activation, signaling and trafficking, or in interaction with other receptors and neuromodulatory systems. All these tools for in-vivo research, and proposed mechanisms at molecular level, have tremendously increased our understanding of δ receptor physiology, and contribute to designing innovative strategies for the treatment of chronic pain and other diseases such as mood disorders.

Figure 1

Sites for delta opioid analgesia. This scheme summarizes sites where delta agonist administration induces analgesia in animal models of chronic pain (see table1). *Abbreviations: DPDPE, (D-Pen2, D-Pen5)-enkephalin; DSLET, (D-Ser2,Leu5)-enkephalin; NRM, Nucleus Raphe Magnus ; RVM, Rostroventral medulla