Nociceptin/orphanin FQ blocks the antinociception induced by mu, kappa and delta opioid agonists on the cold water tail-flick test

Chen, Xiaohong; Geller, Ellen B.; Adler, Martin W.

doi:10.1016/j.ejphar.2006.11.001

Cited by 17 publications

(7 citation statements)

References 36 publications

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“…Anti‐opioid actions cover opiates produced by stress in the original description of N/OFQ by Meunier et al . (), several peptide and non‐peptide opioids selective for opioid receptors (Mogil et al ., ; Chen et al ., ) and electro‐acupuncture (Tian et al ., ). As an anti‐opioid N/OFQ is not unique as there is evidence of similar actions for other peptides such as cholecystokinin (Heinricher et al ., ).…”

Section: Functional Expression Of the N/ofq‐nop Receptor System In Acmentioning

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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Section: Functional Expression Of the N/ofq‐nop Receptor System In Acmentioning

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

View full text Add to dashboard Cite

show abstract

“…However, the pharmacologic actions of N/OFQ, especially with respect to pain in rodents, have not yet been clearly defined. The effect of N/OFQ has been shown to vary from hyperalgesia, allodynia and even analgesia, depending on the route of administration, dose of the drug, genetic differences of the species and characteristics of nociceptive stimuli 5-8. For example, N/OFQ at the supraspinal level, intracisternally or intracerebroventricularly, has been shown to exert pro-nociceptive and hyperalgesic effects in rodents 9,10.…”

Section: Introductionmentioning

confidence: 99%

Effects of Co-Administration of Intrathecal Nociceptin/Orphanin FQ and Opioid Antagonists on Formalin-Induced Pain in Rats

Lee

2013

Yonsei Med J

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PurposeNociceptin/orphanin FQ (N/OFQ) as an endogeneous hexadecapeptide is known to exert antinociceptive effects spinally. The aims of this study were to demonstrate the antinociceptive effects of i.t. N/OFQ and to investigate the possible interaction between N/OFQ and endogenous opioid systems using selective opioid receptor antagonists in rat formalin tests.Materials and MethodsI.t. N/OFQ was injected in different doses (1-10 nmol) via a lumbar catheter prior to a 50 µL injection of 5% formalin into the right hindpaw of rats. Flinching responses were measured from 0-10 min (phase I, an initial acute state) and 11-60 min (phase II, a prolonged tonic state). To observe which opioid receptors are involved in the anti-nociceptive effect of i.t. N/OFQ in the rat-formalin tests, naltrindole (5-20 nmol), β-funaltrexamine (1-10 nmol), and norbinaltorphimine (10 nmol), selective δ-, µ- and κ-opioid receptor antagonists, respectively, were administered intrathecally 5 min after i.t. N/OFQ.ResultsI.t. N/OFQ attenuated the formalin-induced flinching responses in a dose-dependent manner in both phases I and II. I.t. administration of naltrindole and β-funaltrexamine dose-dependently reversed the N/OFQ-induced attenuation of flinching responses in both phases; however, norbinaltorphimine did not.ConclusionI.t. N/OFQ exerted an antinociceptive effect in both phases of the rat-formalin test through the nociceptin opioid peptide receptor. In addition, the results suggested that δ- and µ-opioid receptors, but not κ-opioid receptors, are involved in the antinociceptive effects of N/OFQ in the spinal cord of rats.

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“…N/OFQ has been revealed to exhibit either pro-or anti-nociceptive effects, depending on a series of complex factors such as pain quality, doses and administration routes (12)(13)(14)(15). In terms of rodents, N/OFQ system exhibits antinociceptive effects when peripherally and spinally activated, while pronociceptive effects after supraspinal activation.…”

Section: Discussionmentioning

confidence: 99%

N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

Yan

Han

Zhang

et al. 2020

Preprint

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Background: Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP.Methods: Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression.Results: Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG.Conclusions: N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.

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Nociceptin/orphanin FQ blocks the antinociception induced by mu, kappa and delta opioid agonists on the cold water tail-flick test

Cited by 17 publications

References 36 publications

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

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

Effects of Co-Administration of Intrathecal Nociceptin/Orphanin FQ and Opioid Antagonists on Formalin-Induced Pain in Rats

N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

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