Bidirectional modulatory effect of orphanin FQ on morphine‐induced analgesia: antagonism in brain and potentiation in spinal cord of the rat

Tian, Jin Hua; Xu, Wei; Fang, Yuan; Mogil, Jeffrey S.; Grisel, Judith E.; Grandy, David K.; Han, Jialun

doi:10.1038/sj.bjp.0700942

Cited by 219 publications

(118 citation statements)

References 24 publications

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“…Interestingly, OFQ/N, a 17 amino acid peptide, is structurally similar to the endogenous opioid peptides, in particular to dynorphin A [33,61]. Paradoxically, supraspinal OFQ/N administration induces hyperalgesia [55,61,78] or, at least, blocks the antinociceptive effect of mu, delta and kappa opioid receptor agonists [64,67,92]. OFQ/N was accordingly proposed as an anti-opioid peptide in the brain [63].…”

Section: Introductionmentioning

confidence: 99%

Buprenorphine: A Unique Drug with Complex Pharmacology

Lutfy

Cowan²

2004

280

232

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Buprenorphine, an opioid with mixed agonist-antagonist activity at classical opioid receptors, has been approved recently for the treatment of opioid dependency. Buprenorphine is also used as an analgesic. The buprenorphine dose-response curve is sometimes submaximal, or even bell-shaped, in nociceptive assays, depending upon the nature and intensity of the noxious stimulus. Moreover, buprenorphine, when administered with full agonists, such as morphine, antagonizes the action of these drugs. Partial agonism at the mu opioid receptor and, in some cases, antagonism at the kappa or delta opioid receptor have been considered as possible underlying mechanisms for the ceiling effect and bell-shaped dose-response curve of buprenorphine. While ceiling effects can be explained by partial agonist activity of buprenorphine, the bell-shaped dose-response curve cannot be a consequence of this property of the drug. Recently, buprenorphine has been shown to activate the opioid receptor-like (ORL-1; also known as NOP) receptor. Supraspinal activation of the ORL-1 receptor counteracts the antinociceptive and rewarding actions of morphine, raising the possibility that these actions of buprenorphine can also be altered by its ability to concomitantly activate the ORL-1 receptor. The use of molecular biological techniques has advanced our knowledge regarding the role of opioid receptors in modulation of pain and reward. In particular, generation of opioid receptor knockout mice has proven useful in this regard. Indeed, using knockout mice, we have recently shown that the antinociceptive effect of buprenorphine mediated primarily by the mu opioid receptor is attenuated by the ability of the drug to activate the ORL-1 receptor. Thus, the goal of this review is to provide evidence demonstrating that the ORL-1 receptor plays a functional role not only in the antinociceptive effect of buprenorphine but also in other actions of the drug as well.

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Section: Introductionmentioning

confidence: 99%

Buprenorphine: A Unique Drug with Complex Pharmacology

Lutfy

Cowan²

2004

280

232

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“…administration of very low doses (0.005-0.05 nmoles; Florin et al, 1996). N/OFQ alters responses to nociceptive stimuli (Meunier et al, 1995;Reinscheid et al, 1995;Grisel et al, 1996;Erb et al, 1997;Hao et al, 1997;Helyes et al, 1997;King et al, 1997;Morgan et al, 1997;Tian et al, 1997;Yamamoto et al, 1997;Zhu et al, 1997). It appears not to exert any specific motivational actions in tests of place conditioning, when administered alone (Devine et al, 1996a;Ciccocioppo et al, 2000;Le Pen et al, 2002), but it stimulates feeding behavior (Pomonis et al, 1996;Stratford et al, 1997;Polidori et al, 2000;Ciccocioppo et al, 2002a), blocks morphine place conditioning (Murphy et al, 1999;Ciccocioppo et al, 2000), and interferes with the behaviorallyreinforcing effects of ethanol (Ciccocioppo et al, 1999(Ciccocioppo et al, , 2002bMartin-Fardon et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Nociceptin/Orphanin FQ Increases Anxiety-Related Behavior and Circulating Levels of Corticosterone During Neophobic Tests of Anxiety

Fernandez

Misilmeri

Felger

et al. 2003

Neuropsychopharmacol

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Intracranial administration of nociceptin/orphanin FQ (N/OFQ) increases circulating concentrations of adrenocorticotrophic hormone and corticosterone in unstressed rats, and elevates the responsiveness of these hormones during mild stress. Furthermore, N/OFQ and its cognate receptor are both abundant in a variety of limbic nuclei, and stress exposure decreases neuronal N/OFQ content in forebrain neurons. In light of these and other findings, we examined the potential involvement of N/OFQ in regulation of anxiety-related behaviors in rats. In the open field, elevated plus maze, and dark-light neophobic tests, intracerebroventricular N/OFQ (1.0 pmole-1.0 nmole) increased the expression of anxiety-related behaviors. Specifically, N/OFQ increased the latency to enter, decreased the number of entries into, and decreased the time spent in the exposed or brightly lit environments of all three tests. N/OFQ also enhanced thigmotactic responses in the open field test. The effects of diazepam and of the benzodiazepine inverse agonist FG 7142 were also assessed in independent groups of rats. In all three tests, the behavioral effects of N/OFQ resembled the anxiogenic actions of FG 7142, and contrasted with the anxiolytic actions of diazepam. N/OFQ administration also increased circulating concentrations of corticosterone during anxiety testing, in comparison with the concentrations in vehicle-treated controls. We conclude that N/OFQ administration is anxiogenic, and elevates responsiveness of the hypothalamic pituitary-adrenal axis during neophobic tests of anxiety. This supports the possibility that N/OFQ neurotransmission participates in processing of emotionally-salient and stressful stimuli, and suggests that normal functioning of the N/OFQ system may be important in physiological and psychological well-being.

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“…morphine (Mogil et al, 1996). At the spinal level, intrathecal injection of low concentrations of nociceptin in mice causes allodynia and hyperalgesia (Hara et al, 1997), whereas at higher concentrations this peptide can cause analgesia (King et al, 1997;Tian et al, 1997). These effects are mediated at both a presynaptic site of action in afferent nerve terminals, and at a postsynaptic site of action on spinal interneurons (Neal et al, 1999).…”

mentioning

confidence: 99%

Modification of Nociception and Morphine Tolerance by the Selective Opiate Receptor-Like Orphan Receptor Antagonist (–)-cis-1-Methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111)

Zaratin

Petrone²,

Sbacchi³

et al. 2003

J Pharmacol Exp Ther

142

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ABSTRACT(Ϫ)-cis-1- piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111) is a novel human opiate receptor-like orphan receptor (ORL-1) antagonist that has high affinity for the clonal human ORL-1 receptor (hORL-1 K i ϭ 0.33 nM), selectivity versus -(174-fold), ␦-(6391-fold), and (486-fold)-opioid receptors and is able to inhibit nociceptin signaling via hORL-1 in a whole cell gene reporter assay. SB-612111 has no measurable antinociceptive effects in vivo in the mouse hot-plate test after intravenous administration but is able to antagonize the antimorphine action of nociceptin [ED 50 ϭ 0.69 mg/kg, 95% confidence limit (CL) ϭ 0.34 -1.21]. SB-62111 administration can also reverse tolerance to morphine in this model, established via repeated morphine administration. In addition, intravenous SB-612111 can antagonize nociceptin-induced thermal hyperalgesia in a dose-dependent manner (ED 50 ϭ 0.62 mg/kg i.v., 95% CL ϭ 0.22-1.89) and is effective per se at reversing thermal hyperalgesia in the rat carrageenan inflammatory pain model. These data show that an ORL-1 receptor antagonist may be a useful adjunct to chronic pain therapy with opioids and can be used to treat conditions in which thermal hyperalgesia is a significant component of the pain response.Nociceptin (orphanin FQ) is a 17-amino acid peptide identified as a potent endogenous agonist for the opiate receptorlike orphan receptor (ORL-1), a G protein-coupled receptor with a high degree of structural homology to the classical opioid receptors (Mollereau et al., 1994). Despite the high similarity in sequence between nociceptin and other opioid peptides, notably dynorphin A, nociceptin does not interact with -, ␦-, or -opioid receptors, and opioid peptides do not interact with the ORL-1 receptor (Meunier et al., 1995). Activation of the ORL-1 receptor with nociceptin can enhance cellular K ϩ conductance (Vaughan et al., 1997), inhibit Ca 2ϩ currents associated with N, L, and P/Q calcium channel activation (Knoflach et al., 1996;Connor and Christie, 1998), and block cellular cAMP production (Butour et al., 1997). These signaling mechanisms are represented in areas of the nervous system that are crucial for pain transmission, and nociceptin can act via these pathways to influence, for example, glutamate and GABA release in the periaqueductal gray (Vaughan et al., 1997) and neuronal activity in the dorsal root of the spinal cord (Lai et al., 1997). Furthermore, peptide antagonists of the ORL-1 receptor such as [N-Phe 1 ]nociceptin(1-13)NH 2 and UFP-101 have been shown to inhibit presynaptic 5-hydroxytryptaArticle, publication date, and citation information can be found at

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Bidirectional modulatory effect of orphanin FQ on morphine‐induced analgesia: antagonism in brain and potentiation in spinal cord of the rat

Cited by 219 publications

References 24 publications

Buprenorphine: A Unique Drug with Complex Pharmacology

Buprenorphine: A Unique Drug with Complex Pharmacology

Nociceptin/Orphanin FQ Increases Anxiety-Related Behavior and Circulating Levels of Corticosterone During Neophobic Tests of Anxiety

Modification of Nociception and Morphine Tolerance by the Selective Opiate Receptor-Like Orphan Receptor Antagonist (–)-cis-1-Methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111)

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