As the use of analgesics continues to develop clinically, researchers are gradually turning their focus to the activation of delta-opioid receptors (DOR). The delta-opioid receptor is one of several known opioid receptors, and its potential role in pain modulation has sparked widespread discussion in the medical community. As delta-opioid receptors are better understood, findings could pave the way for the development of safer painkillers.
Delta-opioid receptors exhibit essential pain-relieving effects in animal models, particularly in the modulation of chronic pain.
Due to differences in the expression regions of δ-opioid receptors in different species, the specific role of δ-opioid receptors in pain relief remains to be further clarified. Especially in the human brain, δ-opioid receptors are highly expressed mainly in the basal ganglia and neocortical areas, which may affect their performance in pain regulation. Although there is evidence that activation of delta-opioid receptors can trigger analgesic effects, the specific mechanisms of this effect are not fully understood.
Activation of delta-opioid receptors offers an interesting new approach to pain treatment because it provides a complementary mechanism of action to that of μ-opioid receptors.
Research has found that activation of δ-opioid receptors can significantly enhance the analgesic effect of μ-opioid receptor agonists. As more studies reveal a link, some have begun to propose the use of mixed μ/delta agonists, which may reduce the side effects of current μ-opioid agonists, most notably the risk of respiratory depression.
There is evidence that delta-opioid agonists may cause respiratory depression at high doses but may promote respiratory function at low doses.
For example, delta-opioid receptor agonists such as Deltorphin II and (+)-BW373U86 not only stimulate respiratory function but also prevent the respiratory depressant effects of potent μ-opioid agonists. This feature makes hybrid drugs such as DPI-3290 that target delta-opioid receptors a potential choice for future analgesic drugs, because they can achieve pain relief while reducing the risk of side effects.
However, delta-opioid agonists may still cause seizures at high doses, a side effect that also requires more in-depth research to understand its mechanism and scope. Furthermore, although animal models have shown potential efficacy of delta-opioid agonists in treating depression, results in human trials have been inconsistent.
In a clinical trial conducted in 2008, the selective delta-opioid receptor agonist AZD 2327 did not show significant mood improvement.
The discovery now makes scientists cautious about the role of delta-opioid receptors in mood regulation and calls for further trials to explore their potential therapeutic applications. It is worth noting that δ-opioid receptors may interact with other receptors, such as μ-opioid receptors, which provides new ideas for combined therapies for pain and mood disorders.
Research suggests that interactions between μ/δ-opioid receptors may be important in pain management and mood regulation.
Finally, delta-opioid receptors have also been found to be involved in cardioprotection, reducing the risk of heart disease by improving blood flow supply. This makes drugs that activate delta-opioid receptors not only advantageous in analgesia, but also have other therapeutic benefits. As research in this area continues, future pain medications will be safer and more versatile treatments. In an ever-changing healthcare environment, can we adopt these new ways to improve the patient experience?