Central opioid receptors

Another site of action for opioids is through the regulatory actions of the central nervous system (CNS) on the immune system. Substantial evidence supports the existence of a complex, bidirectional link between the CNS and the immune system (e.g., [65]). Experimental evidence indicates that morphine s immunomodulatory effects involve central opioid receptors. An initial study by Shavit and colleagues [12] found that systemic administration of morphine, but not N-methylmorphine (a form of morphine which does not readily penetrate the blood-brain barrier), produces a naltrexone-reversible suppression of splenic natural killer cell activity in the rat. That same study showed that intracerebroventricular (icv) administration of morphine dose-dependently suppresses... 

The opioids modulate the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. In addition, leucocytes migrate to the site of tissue injury and release opioid peptides, which in turn help counter inflammatory pain. However, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could... 

Naltrexone appears also to be a relatively pure opioid antagonist, but with higher oral efficacy and a longer duration of action than naloxone [35], This is probably due to biotransformation to the active metabolite 6/J-naltrexol (Scheme 3. J), which can cross the blood-brain barrier, contributing to central opioid receptor blockade. These properties make naltrexone suitable for the management of opioid dependence and provide a new and effective modality for the physician treating addicts [36, 38], Alcoholism is another addiction which can possibly be treated with naltrexone [38],... 

Epidural hydromorphone s primary site of action is at endogenous opioid receptors located on neurons in lamina 1-11 (substantia gelatinosa) and lamina V of the spinal dorsal horn. Following epidural administration, hydromorphone enters the spinal cord and activates pre- and postsynaptic mu receptors and suppresses pain transmission. Systemic absorption and activation of central opioid receptors may provide additional analgesia. Hydromorphone is not particularly hydrophilic, and rostral migration in CSF is of lower magnitude than that observed with morphine. Rostral spread of hydromorphone may result in undesirable side effects such as pruritus, nausea and vomiting, and sedation. Epidural hydromorphone is associated with dose-dependent reductions in respiratory rate and minute ventilation however, unlike morphine, delayed-onset respiratory depression is less likely to occur [3,4]. 

A 17 amino acid long peptide sequentially related to opioid peptides in particular dynorphin A. OFQ/N is inactive at the 5, k, and p opioid receptors, but binds to its own NOP receptor (formerly ORL-1, for opioid receptor like-1). In contrast to opioid peptides, OFQ/N has no direct analgesic properties. OFQ/N is the first example for the discovery of a novel neurotransmitter from tissue extracts by using an orphan receptor as bait. Centrally administered in rodents, OFQ/N exerts anxiolytic properties. OFQ/N agonists and antagonists... 

Saito Y, Sharer LR, Epstein LG, Michaels J, Mintz M, Louder M, Golding K, Cvetkovich TA, Blumberg BM (1994) Overexpression of nef as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues. Neurology 44 474-481 Sargeant TJ, Day DJ, Mrkusich EM, Eoo DE, Miller JH (2007) Mu opioid receptors are expressed on radial glia but not migrating neuroblasts in the late embryonic mouse brain. Brain Res 1175 28-38... 

Henriksen G, Willoch P (2008) Imaging of opioid receptors in the central nervous system. Brain 131 1171-1196... 

Morphine may be administered orally, intravenously, or epidurally. An advantage of epidural administration is that it provides effective analgesia while minimizing the central depressant effects associated with systemic administration. The mechanism of action with the epidural route of administration involves opioid receptors on the cell bodies of first-order sensory neurons in the dorsal root ganglia as well as their axon terminals in the dorsal hom. Stimulation of these receptors inhibits release of substance P and interrupts transmission of the pain signal to the second-order sensory neuron. 

Simonin F., Gaveriaux-Ruff C., Befort K. et al. k-Opioid receptor in humans cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system. Proc. Natl. Acad. Sci. U.S.A. 92 7006, 1995. 

Ding Y, Kaneko T, Nomura S, Mixuno N. Immunohistochemical localization of mu opioid receptors in the central nervous system of the rat. J Comp Neurol 1996 367 375-402. 

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