Up-regulation of ORL-1 receptors in spinal tissue of allodynic rats after sciatic nerve injury

Briscini, Luca; Corradini, Laura; Ongini, Ennio; Bertorelli, Rosalia

doi:10.1016/s0014-2999(02)01833-2

Cited by 89 publications

(77 citation statements)

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“…Furthermore, SR16835, which is inactive in blocking tail flick acute pain, was able to attenuate SNL-induced mechanical allodynia, an action also blocked by SB-612111 (Khroyan et al, 2011). These results are consistent with chronic pain-, as well as chronic inflammation-induced changes in the levels of NOP receptor mRNA, N/OFQ peptide levels, and ppN/OFQ mRNA levels in rodents (Andoh et al, 1997;Itoh et al, 2001;Briscini et al, 2002;Witta et al, 2003) and humans (Raffaeli et al, 2006) and once again suggest that NOP agonists might have better success in treatment of chronic or inflammatory rather than nociceptive acute pain.…”

Section: B Bifunctional Compoundssupporting

confidence: 76%

“…As with acute pain, N/OFQ has antiallodynic and antihyperalgesic activity after intrathecal administration in models of chronic neuropathic and inflammatory pain (Hao et al, 1998;Corradini et al, 2001). However, the levels of NOP receptors and N/OFQ change in chronic or inflammatory pain states, suggesting a sensitization of the NOP system (Andoh et al, 1997;Sun et al, 2001;Briscini et al, 2002;Ma et al, 2005). Furthermore, both preproN/OFQ(2/2) [ppN/OFQ(2/2)] and NOP(2/2)mice display increased inflammatory hyperalgesia in the formalin assay, but not in an acute pain assay (Depner et al, 2003), similar to NOP(2/2) rats .…”

Section: Biologic Actions Of Nociceptin Opioid Peptide Receptorsmentioning

confidence: 99%

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Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

et al. 2016

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The NOP receptor (nociceptin/orphanin FQ opioid peptide receptor) is the most recently discovered member of the opioid receptor family and, together with its endogenous ligand, N/OFQ, make up the fourth members of the opioid receptor and opioid peptide family. Because of its more recent discovery, an understanding of the cellular and behavioral actions induced by NOP receptor activation are less well developed than for the other members of the opioid receptor family. All of these factors are important because NOP receptor activation has a clear modulatory role on mu opioid receptor-mediated actions and thereby affects opioid analgesia, tolerance development, and reward. In addition to opioid modulatory actions, NOP receptor activation has important effects on motor function and other physiologic processes. This review discusses how NOP pharmacology intersects, contrasts, and interacts with the mu opioid receptor in terms of tertiary structure and mechanism of receptor activation; location of receptors in the central nervous system; mechanisms of desensitization and downregulation; cellular actions; intracellular signal transduction pathways; and behavioral actions with respect to analgesia, tolerance, dependence, and reward. This is followed by a discussion of the agonists and antagonists that have most contributed to our current knowledge. Because NOP receptors are highly expressed in brain and spinal cord and NOP receptor activation sometimes synergizes with mu receptor-mediated actions and sometimes opposes them, an understanding of NOP receptor pharmacology in the context of these interactions with the opioid receptors will be crucial to the development of novel therapeutics that engage the NOP receptor

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Section: B Bifunctional Compoundssupporting

confidence: 76%

Section: Biologic Actions Of Nociceptin Opioid Peptide Receptorsmentioning

confidence: 99%

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

et al. 2016

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“…at ASPET Journals on May 11, 2018 jpet.aspetjournals.org dorsal root ganglia of neuropathic CCI rats (Briscini et al, 2002;Mika et al, 2004). A significant increase in brain N/OFQ immunoreactivity has also been demonstrated in SNL rats (Sun et al, 2001), as well as an increase in NOP receptors in superficial laminae of the rat spinal cord subsequent to CFA injection, as determined by in vitro autoradiography (Jia et al, 1998).…”

Section: Nop Agonists In Acute Versus Chronic Pain 691mentioning

confidence: 92%

“…In particular, there is an increase in NOP receptor mRNA in various brain regions, dorsal root ganglia, and spinal cord of CCI rats (Briscini et al, 2002;Mika et al, 2004;Ma et al, 2005). There is also an increase in NOP receptors in superficial laminae of the rat spinal cord subsequent to CFA injection, as determined by in vitro autoradiography (Jia et al, 1998).…”

Section: Introductionmentioning

confidence: 93%

Differential Effects of Nociceptin/Orphanin FQ (NOP) Receptor Agonists in Acute versus Chronic Pain: Studies with Bifunctional NOP/μ Receptor Agonists in the Sciatic Nerve Ligation Chronic Pain Model in Mice

Khroyan¹,

Polgar²,

Orduna³

et al. 2011

J Pharmacol Exp Ther

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1-(1-Cyclooctylpiperidin-4-yl)-indolin-2-one (SR14150) and 1-(1-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)piperidinl-4-yl)-indolin-2-one (SR16835) are moderately selective nociceptin/ orphanin FQ (NOP) receptor agonists. In the [35 S]guanosine 5Ј-O-(3-thiotriphosphate) assay in vitro, SR14150 is a partial agonist at both the NOP and -opioid receptors, whereas SR16835 is a full agonist at the NOP receptor and has low efficacy at receptors. These compounds were tested for antinociceptive and antiallodynic activity, using mice in chronic pain, subsequent to spinal nerve ligation (SNL) surgery. When administered subcutaneously to mice after SNL surgery, SR14150 but not SR16835 increased tail-flick latency, which was blocked by the opioid antagonist naloxone, but not by the NOP receptor antagonist (Ϫ)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111). In contrast, both SR14150 and SR16835 had antiallodynic activity when mechanical allodynia was measured with von Frey monofilaments. This effect was completely blocked by SB-612111 but not by naloxone. On the other hand, morphine antinociception and antiallodynia were both blocked by naloxone and potentiated by SB-612111. These results indicate that, in mice, circuitry mediating antinociceptive activity in acute and chronic pain states is different. It is possible that during a chronic pain state, an up-regulated NOP system in the spinal cord leads to NOP receptor-mediated antiallodynia, which is blocked by NOP antagonists. However, supraspinal up-regulation could lead to an attenuation of morphine antinociception and antiallodynia, which can be alleviated by an NOP receptor antagonist. Thus, although neither NOP agonists nor antagonists are effective as analgesics in acute pain, they may have efficacy as analgesics, either alone or in combination with morphine, for treatment of chronic pain.

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“…Compared with studies investigating CNS effects of N/OFQ, only a very limited number of reports have addressed peripheral actions of N/OFQ on nociceptors. Both the N/OFQ and the NOP receptor are expressed at rather low levels in dorsal root ganglion cells, but NOP receptor expression increases after sciatic nerve injury (Briscini et al, 2002). A functional role of peripheral NOP receptors has been demonstrated by Inoue et al (1998), who reported that N/OFQ injected intraplantar at very low (femtomole) doses induced Ca 2ϩ -dependent substance P release thereby evoking nociceptive flexor reflexes.…”

mentioning

confidence: 97%

Nociceptin/Orphanin FQ and Its Receptor—Potential Targets for Pain Therapy?

Zeilhofer¹,

Calò²

2003

J Pharmacol Exp Ther

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The neuropeptide nociceptin, also called orphanin FQ (N/OFQ), is the endogenous agonist of the N/OFQ peptide receptor (NOP receptor). Both N/OFQ and the NOP receptor share a high degree of homology with classical opioid peptides and opioid receptors, respectively, and use similar signal transduction pathways as classical opioids. The NOP receptor has thus been regarded as the fourth member of the opioid receptor family. Despite this close relationship, 7 years of research have demonstrated that the N/OFQ system has a distinct pharmacological profile and serves different physiological functions. In particular, its role in the control of pain and analgesia at different levels of integration appears quite different from that of classical opioids. The recent development of specific antagonists at the NOP receptor and of NOP receptor or N/OFQ precursor knock-out mice have generated new insights into the role of N/OFQ in pain processing and help to evaluate the N/OFQ-NOP system as a potential target for new analgesic drugs.While acute-particularly post-traumatic and postsurgical pain can be treated satisfactorily with available analgesics in most cases-chronic inflammatory and neuropathic pain often responds only poorly. The identification of novel targets for analgesic therapy is therefore a major focus in current pharmacological research. Chronic pain states are frequently accompanied by an increased pain sensitivity, which can appear as hyperalgesia, an increased sensitivity to noxious stimuli, or allodynia, a painful sensation of usually innocuous stimuli. N/OFQ has repeatedly been implicated in the development and/or modulation of both phenomena and has thus attracted significant attention in current pain research.The discovery of N/OFQ is a prominent example of so called reverse pharmacology in which a receptor was known before the corresponding ligand could be identified (Civelli et al., 1998). Soon after the discovery of the ␦ opioid (DOP) receptor by expression cloning molecular biologists have not only identified the expected and (MOP and KOP) opioid receptors, but also a fourth unperceived receptor, which does not bind classical opioids. The human homolog of this receptor has therefore been termed opioid receptor-like 1 receptor (Mollereau et al., 1994). Only 1 year after its discovery, a 17 amino acid neuropeptide was identified as the endogenous agonist by two independent groups and called nociceptin (Meunier et al., 1995) or orphanin FQ (Reinscheid et al., 1995). Both the peptide and its receptor, now called N/OFQ peptide (NOP) receptor, share a high degree of homology with classical opioid peptides (namely dynorphin A) and classical opioid receptors (namely the opioid peptide receptor). A first series of behavioral tests has suggested that this peptide was pro-rather than antinociceptive, when injected intracerebroventricularly (i.c.v.). This effect led Meunier et al. (1995) to coin the term nociceptin. Reinscheid et al. (1995) called the peptide orphanin FQ, indicating that the peptide activat...

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Up-regulation of ORL-1 receptors in spinal tissue of allodynic rats after sciatic nerve injury

Cited by 89 publications

References 32 publications

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

Differential Effects of Nociceptin/Orphanin FQ (NOP) Receptor Agonists in Acute versus Chronic Pain: Studies with Bifunctional NOP/μ Receptor Agonists in the Sciatic Nerve Ligation Chronic Pain Model in Mice

Nociceptin/Orphanin FQ and Its Receptor—Potential Targets for Pain Therapy?

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