Mechanisms of Mu-Opioid Receptors Regulation

INTRODUCTION: Opioid receptors are key targets for the relief of acute and chronic pain. Unfortunately, the therapeutic effect on these receptors is associated with significant disadvantages, including dependence, tolerance, and the occurrence of side and undesirable effects. The Mu-opioid receptor is a cellular mediator responsible for the action of the most commonly used opioids, and is a typical G-protein coupled receptor for which new concepts of pharmacological research have been formulated. CONCLUSION: Research in recent decades has shown a need to develop new pharmaceutical agents aimed at reducing the disadvantages of opioid substances while maintaining their effectiveness. The search for multi-purpose painkillers that act on heterodimers is promising, which may be therapeutically useful due to the complex nature of many pain syndromes involving interactions between multiple signaling pathways. The complex and paradoxical interaction between neurokinin and opioid pathways is also being investigated. It became clear that pain in nociceptive neurons is associated with the activation of the neurokinin-1 receptor by substance P, while pain relief is primarily mediated by opioids through the mu-opioid receptors. At the same time, neurokinin-1 receptor signaling also increases resensitization and recirculation in mu-opioid receptors of sensory neurons. And, since opioid peptides are not the only modulators of pain signals in the nervous system, a promising approach in the search for more effective analgesics with limited undesirable effects is to combine opioids with other neurotransmitters involved in pain perception, in particular, substance P.