Opioids and the neuroimmune axis
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概要
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Clinically opioids are immunomodulatory where a general depression is reported. In addition, immunecells carry endogenous opioid peptides to sites of inflammation where opioid receptors on peripheral nerves areupregulated. Release of these endogenous opioids produces a degree of analgesia and completes the neuroimmune axis.The expression of opioid receptors on immune cells that deliver these opioid peptides, is contentious and is the basis ofthis short review. There are several papers reporting expression of opioid receptors on peripheral blood mononuclearcells （PBMCs） using a variety of in vitro biochemical/pharmacological techniques. Equally there are studies failingto detect these receptors. We have recently undertaken a detailed volunteer study to determine the expression ofclassical naloxone sensitive MOP, DOP and KOP and non-classical naloxone insensitive NOP receptors. We initiallyfocused our attention on the MOP receptor as the main clinical analgesic target. Using radioligand binding, FACSwith opioid receptor antibodies and PCR we have failed to detect all classical opioid receptors. In contrast, using PCRtechniques the non-classical NOP receptor is present in all volunteer samples examined along with its endogenouspeptide ligand nociceptin/orphanin F/Q （N/OFQ）. As both the peptide （N/OFQ） and receptor （NOP） are presentwe suggest that there may be a feedback loop such that peripherally delivered N/OFQ（ to infl ammatory site） wouldproduce both a classical analgesic response and then feedback to modulate PMBC function. The nature of that functionremains to be determined but could include release of further N/OFQ, activation of other immune cells or chemotaxis.Opioids have been used by man for centuries for the relief of pain. Morphine is the most widely used opioid in theclinic and is considered the gold standard to which all others are compared. In addition to producing analgesia, opioidadministration also produces other eff ects including; respiratory depression, gastrointestinal-inhibition, tolerance anddependence and immunomodulationbasic summaries see1-4）. Patients receiving long term opioid treatment display signs ofimmunodepression; it has been suggested that this may occur either as a direct eff ect of opioids on circulating immunecells or via a central action （see below）. Neuronal opioid receptors are up-regulated in peripheral infl ammation andStein and colleagues（ in particular） have shown that release of these endogenous opioids from circulating immune cellsproduces a degree of analgesia and complete the neuroimmune axis5）, i.e., immunomodulation of neuronal activity. Theexpression of opioid receptors on the circulating immune cells that deliver these opioid peptides remains unclear and isthe focus of this short review.
- 弘前大学の論文
著者
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Williams John
Department Of Cardiovascular Sciences (pharmacology And Therapeutics Group) Division Of Anaesthesia
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Williams John
Department Of Botany And Centre For Plant Biotechnology 25 Willcocks Street University Of Toronto
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Lambert David
Department of Cardiovascular Sciences (Pharmacology and Therapeutics Group), Division of Anaesthesia
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Thompson Jonathan
Department of Cardiovascular Sciences (Pharmacology and Therapeutics Group), Division of Anaesthesia
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Lambert David
Department Of Cardiovascular Sciences (pharmacology And Therapeutics Group) Division Of Anaesthesia
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Thompson Jonathan
Department Of Cardiovascular Sciences (pharmacology And Therapeutics Group) Division Of Anaesthesia
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