Conventional opioids are known as the most effective painkillers. Their prolonged use can lead to addiction, which limits the effectiveness of pain therapy. When used as prescribed and accurately monitored, these drugs are elective in the treatment of moderate to severe pain. Unfortunately, their therapeutic action is associated with side effects like respiratory depression, somnolence, constipation, and dependence and analgesic tolerance which represents a limitation for their clinical use. Opioid abuse has also placed a growing burden on health services through hospitalization and emergency room visits and requirements.

Our understanding of the different mechanisms underlying nociception and pain has changed over time. Pain is now considered as a complex neurological disease and thus requires adapted therapeutic approaches. Its prevention has become understood as a complex process that involves numerous sensitive nodes of the brain and, therefore, a comprehensive pain prevention and management strategy is required. Translational, clinical, and basic science research continues to play an important part in combatting those issues through generating new knowledge and innovations in the treatment of pain.

The past several years have seen a number of advances in identifying the next generation of analgesic agents with the overall goal to separate the analgesic properties from their unwanted side effects. Therefore, this Special Issue is dedicated to cover original research findings and relevant review articles that may improve our understanding about the potential use of opioid analgesics in the treatment of pain. We encourage both research scientists and clinicians from different disciplines ranging from opioid pharmacology to medicinal chemistry and genetics of opioid use disorders to submit their papers. Randomized controlled clinical trials and meta-analyses reflecting new knowledge and providing a clear and exhaustive view in this field are also invited to contribute in this Special Issue.

Potential topics include but are not limited to the following:

• Novel insights into opioid drug design, evaluation, and pharmacological actions
• Translational and basic science research on opioids and opioid-receptor mediated actions for pain prevention and management
• Update regarding the generation of safer opioid analgesics with reduced side effects
• Mechanism-based approach of opioid use for selective treatment of different types of pain