Abstract
Objective – An analysis of the basic science and clinical publications found in PubMed, Medline, and Web of Science. The search covered modern laboratory and clinical mechanisms of peripheral mu opioid analgesia, the role of peripheral mu receptors in systemic analgesia and the development of tolerance to the analgesic effect of opioids. The review discusses the regulatory mechanisms of synthesis and transport of mu-opioid receptors in the primary afferent neurons and the molecular mechanisms responsible for modulating the conduction of nociceptive information from the periphery to the spinal cord. According to some authors, the peripheral component can account for 50-90% of the total analgesic effect after the systemic administration of morphine and methadone. The review reports on the important role of glycoprotein-P and the blood-brain barrier transport system in modulating the peripheral component of the analgesic effect of morphine as well as the synergistic interaction between central and peripheral mu receptors. The results of the reviewed studies convincingly show the key role of peripheral mu receptors in the development of tolerance to the analgesic effect of morphine after its systemic administration. The mechanisms of opioid tolerance also involve peripheral anti-opioid, pronociceptive systems such as NMDA receptors. It is well known that the same mechanisms are involved in maintaining peripheral hyperalgesia and allodynia. The development of analgesic drugs that act on peripheral antinociceptive systems offers a promising perspective on the possible treatment of acute and chronic pain.
Highlights
An analysis of the basic science and clinical publications found in PubMed, Medline, and Web of Science
The results of our studies convincingly show the key role of peripheral mu and NMDA receptors in the development of tolerance to the analgesic effect of morphine after its systemic administration
To study the peripheral mechanisms involved in the development of opioid tolerance, we have developed a method for the topical administration of drugs and investigated the role of peripheral NMDA receptors in the expression of tolerance
Summary
An analysis of the basic science and clinical publications found in PubMed, Medline, and Web of Science. После системного (внутривенного, внутримышечного, подкожного, перорального) введения морфина и его аналогов активируются многочисленные мю-опиоидные антиноцицептивные механизмы в центральной и периферической нервной системе (рис.): morphine and its analogs, numerous mu-opioid anti-nociceptive mechanisms are activated in the central and peripheral nervous system (Fig.): Fig. Central and peripheral sites of the morphine analgesia
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