Functional study of neurons expressing mu-opioid receptor in the dorsal horn of the rat spinal cord
Opioids (morphine and its analogues) belong to the most effective analgesics. Unfortunately, undesired side effects, such as depression of respiration, constipation, mood disorder, tolerance and dependence may appear during their application. It is well known that these drugs act on specific mu-opioid receptors. The main goal is to design morphine analogues with improved pharmacological properties to activate the mu-receptor without side effects. For this, it is necessary to know the distribution, localization, physiological and pharmacological properties of the mu-receptor in the central nervous system.
The spinal cord is one of the main target areas of the opioid analgesia where the mu-agonists act both pre- and postsynaptically. The role of the pre- and postsynaptic mechanisms has not been fully determined to date. The antibody against the mu-receptor outlines a specific cell population in lamina II of the spinal dorsal horn. The huge receptor density on their soma and dendrites suggests their possible role in the opioid analgesia, but the underlying mechanisms and their place in the spinal neuronal networks are still unknown.
In order to understand the mechanisms of opioid analgesia at cellular and network level in the spinal cord, we intend to use combined techniques such as physiology, pharmacology, fluorescent immunocytochemistry, confocal and electron microscopy and in situ hybridization. We expect that our results could contribute to the development of more effective therapy of patients suffering from severe pain.