The Nociceptin/Orphanin FQ System Is Modulated in Patients Admitted to ICU with Sepsis and after Cardiopulmonary Bypass

Thompson, Jonathan P.; Serrano-Gomez, A; McDonald, John; Ladak, Nadia; Bowrey, Sarah; Lambert, David G.

doi:10.1371/journal.pone.0076682

Cited by 22 publications

(29 citation statements)

References 49 publications

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“…Together, opioid receptor mRNAs appear to be expressed at relatively low levels in immune cells as compared to neuronal tissue or opioid receptor-expressing immune cell lines (88-91, 109, 110, 121, 122). Additionally, opioid receptor mRNA levels in immune cells can be modified (elevated or diminished) by pathological conditions or pharmacological treatments in vivo (97,99,110,112,117). These issues need to be considered in order to obtain sufficient amount of tissue (leukocyte numbers) for the analysis.…”

Section: Immune Cellsmentioning

confidence: 99%

Opioid Receptors in Immune and Glial Cells—Implications for Pain Control

2020

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neurons can induce analgesia in animal models, but the most clinically relevant are MOP receptor agonists (e.g., morphine, fentanyl). Opioids can also affect the function of immune cells, and their actions in relation to immunosuppression and infections have been widely discussed. Here, we analyze the expression and the role of opioid receptors in peripheral immune cells and glia in the modulation of pain. All four opioid receptors have been identified at the mRNA and protein levels in immune cells (lymphocytes, granulocytes, monocytes, macrophages) in humans, rhesus monkeys, rats or mice. Activation of leukocyte MOP, DOP, and KOP receptors was recently reported to attenuate pain after nerve injury in mice. This involved intracellular Ca 2+ -regulated release of opioid peptides from immune cells, which subsequently activated MOP, DOP, and KOP receptors on peripheral neurons. There is no evidence of pain modulation by leukocyte NOP receptors. More good quality studies are needed to verify the presence of DOP, KOP, and NOP receptors in native glia. Although still questioned, MOP receptors might be expressed in brain or spinal cord microglia and astrocytes in humans, mice, and rats. Morphine acting at spinal cord microglia is often reported to induce hyperalgesia in rodents. However, most studies used animals without pathological pain and/or unconventional paradigms (e.g., high or ultra-low doses, pain assessment after abrupt discontinuation of chronic morphine treatment). Therefore, the opioid-induced hyperalgesia can be viewed in the context of dependence/withdrawal rather than pain management, in line with clinical reports. There is convincing evidence of analgesic effects mediated by immune cell-derived opioid peptides in animal models and in humans. Together, MOP, DOP, and KOP receptors, and opioid peptides in immune cells can ameliorate pathological pain. The relevance of NOP receptors and N/OFQ in leukocytes, and of all opioid receptors, opioid peptides and N/OFQ in native glia for pain control is yet to be clarified.

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Section: Immune Cellsmentioning

confidence: 99%

Opioid Receptors in Immune and Glial Cells—Implications for Pain Control

2020

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“…In line with this wide distribution of the N/OFQ-NOP receptor system, N/OFQ modulates many physiological responses/systems, including anxiety (Jenck et al, 1997), food intake (Pomonis et al, 1996), learning and memory (Sandin et al, 1997), locomotor activity (Reinscheid et al, 1995;Florin et al, 1996), respiratory (Corboz et al, 2000;Takita et al, 2003;Takita and Morimoto, 2008;Singh et al, 2013), immune (Peluso et al, 2001;Serhan et al, 2001), urinary bladder Lazzeri et al, 2001;, cardiovascular and renal functions (Kapusta et al, 1997). NOP receptors identified on pre-and/or postganglionic sympathetic and parasympathetic nerve fibres and innervating blood vessels and heart are involved in the cardiovascular effects of N/OFQ, and might play a role in the pathophysiology of inflammation, arterial hypertension and cardiac or brain circulatory ischaemia (Malinowska et al, 2002;Serrano-Gomez et al, 2011;Brookes et al, 2013;Thompson et al, 2013).…”

Section: Cellular Nop Receptor Expression and Function In Tissuesmentioning

confidence: 99%

Functional plasticity of the N/OFQ‐NOP receptor system determines analgesic properties of NOP receptor agonists

Schröder¹,

Lambert

et al. 2014

British J Pharmacology

113

180

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Despite high sequence similarity between NOP (nociceptin/orphanin FQ opioid peptide) and opioid receptors, marked differences in endogenous ligand selectivity, signal transduction, phosphorylation, desensitization, internalization and trafficking have been identified; underscoring the evolutionary difference between NOP and opioid receptors. Activation of NOP receptors affects nociceptive transmission in a site-specific manner, with antinociceptive effects prevailing after peripheral and spinal activation, and pronociceptive effects after supraspinal activation in rodents. The net effect of systemically administered NOP receptor agonists on nociception is proposed to depend on the relative contribution of peripheral, spinal and supraspinal activation, and this may depend on experimental conditions. Functional expression and regulation of NOP receptors at peripheral and central sites of the nociceptive pathway exhibits a high degree of plasticity under conditions of neuropathic and inflammatory pain. In rodents, systemically administered NOP receptor agonists exerted antihypersensitive effects in models of neuropathic and inflammatory pain. However, they were largely ineffective in acute pain while concomitantly evoking severe motor side effects. In contrast, systemic administration of NOP receptor agonists to non-human primates (NHPs) exerted potent and efficacious antinociception in the absence of motor and sedative side effects. The reason for this species difference with respect to antinociceptive efficacy and tolerability is not clear. Moreover, co-activation of NOP and μ-opioid peptide (MOP) receptors synergistically produced antinociception in NHPs. Hence, both selective NOP receptor as well as NOP/MOP receptor agonists may hold potential for clinical use as analgesics effective in conditions of acute and chronic pain. AbbreviationsCCI, chronic constriction injury; CFA, complete Freund's adjuvant; CPP, conditioned place preference; DOP, δ-opioid peptide; DRG, dorsal root ganglion; i.c.v., intracerebroventricular; i.pl., intraplantar; i.t., intrathecal; KOP, κ-opioid peptide; MOP, μ-opioid peptide; N/OFQ, nociceptin/orphaninFQ; NHP, non-human primate; NOP, nociceptin/orphaninFQ opioid peptide; NST, nocistatin; PAG, periaqueductal grey; RVM, rostral ventromedial medulla; SNL, spinal nerve ligation; WDR, wide dynamic range IntroductionIn 1994, soon after the cloning of μ-, δ-and κ-opioid receptors (MOP, DOP and KOP, respectively), several groups identified a GPCR with high homology to opioid receptors (Bunzow et al., 1994;Fukuda et al., 1994;Mollereau et al., 1994;Nishi et al., 1994;Wang et al., 1994; for receptor nomenclature see Alexander et al., 2013a), but very low affinity for opioid BJP British Journal of Pharmacology DOI:10.1111/bph.12744 www.brjpharmacol.org British Journal of Pharmacology (2014) 171 3777-3800 3777© 2014 The British Pharmacological Society ligands. Thus, this receptor was named opioid receptor like 1 (ORL1). In 1995, two groups independently identified the endogenous ORL1-ligand, ...

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“…Severe sepsis is accompanied by one of the following conditions: cardiovascular dysfunction, respiratory distress syndrome, or dysfunction of 2 or more other organs (Thompson et al, 2013).…”

Section: Study Participantsmentioning

confidence: 99%