Dynamic Opioid Receptor Regulation in the Periphery

Opioids serve a vital role in the current analgesic array of treatment options. They are useful in acute instances involving severe pain associated with trauma, surgery, and terminal diseases such as cancer. In the past three decades, multiple receptor isoforms and conformations have been reported throughout literature. Most of these studies conducted systemic analyses of opioid receptor function, often generalizing findings from receptor systems in central nervous tissue or exogenously expressing immortalized cell lines as common mechanisms throughout physiology. However, a culmination of innovative experimental data indicates that opioid receptor systems are differentially modulated depending on their anatomic expression profile. Importantly, opioid receptors expressed in the peripheral nervous system undergo regulation uncommon to similar receptors expressed in central nervous system tissues. This distinctive characteristic begs one to question whether peripheral opioid receptors maintain anatomically unique roles, and whether they may serve an analgesic advantage in providing pain relief without promoting addiction.