Opioids are powerful drugs used by humans for centuries to relieve pain and are still frequently used as pain treatment in current clinical practice. Medicinal opioids primarily target the mu opioid receptor (MOR), and MOR activation produces unmatched pain-alleviating properties, as well as side effects such as strong rewarding effects, and thus abuse potential, and respiratory depression contributing to death during overdose. Therefore, the ultimate goal is to create opioid pain-relievers with reduced respiratory depression and thus fewer chances of lethality. Efforts are also underway to reduce the euphoric effects of opioids and avoid abuse liability. In this review, recent advances in basic science methodology used to understand MOR pharmacology and activities will be summarized. The focus of the review will be to describe current technological advances that enable the study of opioid analgesics from subcellular mechanisms to mesoscale network responses. These advances in understanding MOR physiological responses will help to improve knowledge and future design of opioid analgesics
