Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene

Ueda, Hiroshi; Yamaguchi, Taku; Tokuyama, Shogo; Inoue, Makoto; Nishi, Miyuki; Takeshima, Hiroshi

doi:10.1016/s0304-3940(97)00832-x

Cited by 128 publications

(75 citation statements)

References 15 publications

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“…Interestingly the antinociceptive effect of morphine was reduced in NOP( À/ À ) compared to NOP(þ /þ) rats. This finding contrasts with that reported in mice where the analgesic effect of morphine was similar in NOP( þ/ þ) and NOP ( À/ À ) animals (Mamiya et al, 2001;Ueda et al, 1997). This might suggest an involvement of N/OFQergic signaling in the antinociceptive action of spinal morphine in rats but not in mice.…”

Section: Discussioncontrasting

confidence: 96%

Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats

Micheli

Mannelli

Guerrini

et al. 2015

European Journal of Pharmacology

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a b s t r a c tSevere pain occurs in the context of many diseases and conditions and is a leading cause of disability. Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of the N/OFQ peptide (NOP) receptor. This peptidergic system controls pain transmission and in particular spinally administered N/OFQ has robust antinociceptive properties.The aim of this study was to investigate the spinal antinociceptive properties of NOP peptide agonists after acute and subchronic treatment in rats. Doses unable to alter motor coordination were selected. UFP-112 (full NOP agonist) and UFP-113 (partial NOP agonist) were administered intrathecally (i.t.) by spinal catheterization. Acute injection of UFP-112 induced antinociceptive response at lower dosages (0.03-1 nmol i.t.) compared to morphine and similar to N/OFQ. UFP-113 was effective in a 0.001-1 nmol i.t. dose range. The antinociceptive effects of NOP ligands were no longer evident in rats knockout for the NOP gene, while those of morphine were maintained. The continuous spinal infusion (by osmotic pumps) of 0.1 nmol/h UFP-112 and UFP-113 showed antinociceptive action comparable to 1-3 nmol/h morphine or N/OFQ. The antinociceptive effect of morphine progressively decreased and was no longer significant after 6 days of treatment. Similar results were obtained with N/OFQ, UFP-112, and UFP-113. The acute i.t. injection of morphine in animals tolerant to N/OFQ and UFP-112 evoked analgesic effects. Neither morphine nor N/OFQ induced antinociceptive effects in morphine-and UFP-113-tolerant rats. In conclusion this study highlights the analgesic efficacy and potency of UFP-112 and UFP-113 underlining the relevance of NOP system in analgesia.

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Section: Discussioncontrasting

confidence: 96%

Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats

Micheli

Mannelli

Guerrini

et al. 2015

European Journal of Pharmacology

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“…In support of this notion, intracerebroventricular injection of an antibody raised against OFQ/N partially reversed the expression of morphine tolerance [93]. Moreover, morphine tolerance is partially inhibited in mice lacking the ORL-1 receptor [96].…”

Section: The Role Of Orl-1 Receptors In Tolerance To Buprenorphinementioning

confidence: 71%

“…As stated above, the ORL-1 and classical opioid receptor systems represent two opposing mechanisms of pain modulation [55]; thus, it was proposed that the auto-inhibitory mechanism occurs through activation of the ORL-1 receptor, i.e., the mu opioid receptor-mediated antinociceptive effect of buprenorphine is attenuated by its ability to concomitantly activate the ORL-1 receptor. Consistent with this hypothesis, the antinociceptive effect of buprenorphine is greater in mice lacking the ORL-1 receptor [53], whereas the antinociceptive effect of morphine, which does not interact with the ORL-1 receptor [53], is not altered in these mice [53,96]. Thus, it is possible that the antinociceptive efficacy of buprenorphine is modified by concomitant activation of ORL-1 receptors.…”

Section: The Role Of Orl-1 Receptors In the Antinociceptive Effect Ofmentioning

confidence: 73%

Buprenorphine: A Unique Drug with Complex Pharmacology

Lutfy

Cowan²

2004

275

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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“…Spinal effects include analgesia and potentiation of morphine-induced analgesia 29 . Inactivation of the nociceptin receptor ORL1 leads to a markedly attenuated tolerance to the analgesic effects of morphine but without modification of the basal nociceptive threshold 30,31 . These actions are markedly similar to those we observed for PrRP.…”

Section: Discussionmentioning

confidence: 99%

The prolactin-releasing peptide antagonizes the opioid system through its receptor GPR10

et al. 2005

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Prolactin-releasing peptide (PrRP) and its receptor G protein-coupled receptor 10 (GPR10) are expressed in brain areas involved in the processing of nociceptive signals. We investigated the role of this new neuropeptidergic system in GPR10-knockout mice. These mice had higher nociceptive thresholds and stronger stress-induced analgesia than wild-type mice, differences that were suppressed by naloxone treatment. In addition, potentiation of morphine-induced antinociception and reduction of morphine tolerance were observed in mutants. Intracerebroventricular administration of PrRP in wild-type mice promoted hyperalgesia and reversed morphine-induced antinociception. PrRP administration had no effect on GPR10-mutant mice, showing that its effects are mediated by GPR10. Anti-opioid effects of neuropeptide FF were found to require a functional PrRP-GPR10 system. Finally, GPR10 deficiency enhanced the acquisition of morphine-induced conditioned place preference and decreased the severity of naloxone-precipitated morphine withdrawal syndrome. Altogether, our data identify the PrRP-GPR10 system as a new and potent negative modulator of the opioid system.Opiate drugs, the prototype of which is morphine, are used largely for the treatment of severe pain. However, the prolonged use of opiate drugs induces a behavioral adaptation that results in the development of tolerance and dependence 1 . Although these adaptive mechanisms have been known for decades, the underlying pathophysiological pathways have not been fully clarified. It has been proposed that the opioid receptor signaling pathway is adaptively regulated at the cellular level, although more recently a growing contribution of the plasticity of neuronal networks involving opioidergic neurons has been recognized. In support of this latter hypothesis, a number of neuropeptides, including cholecystokinin (CCK) 2 , neuropeptide FF (NPFF) 3 and nociceptin (orphanin FQ) 4 , have been proposed as modulators of the opioid system. These various peptidergic pathways are collectively designated as an anti-opioid system. However, the action of individual peptides on the opioid pathway and on the processing of nociceptive signals is complex and some aspects remain controversial, particularly as the behavioral consequences can vary depending on the injection site of these peptides and the precise experimental setup 5,6 . Among these peptides, NPFF, which belongs to the RF-amide peptide family, was shown (among other actions) to regulate blood pressure 7 , prolactin release 8 and nociceptive signal processing 9 . Prolactin-releasing peptide (PrRP) has recently been identified as an additional member of the mammalian RF-amide peptide family, following its isolation as the natural agonist of the previously orphan GPR10 (ref. 10) (also known as hGR3 in human or UHR-1 in rat). Intracerebroventricular (i.c.v.) administration of PrRP affects feeding behavior 11 , blood pressure 12 and neuroendocrine processes, such as corticotropin-releasing hormone (CRH) 13 and oxytocin 14 release.In a...

show abstract

Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene

Cited by 128 publications

References 15 publications

Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats

Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats

Buprenorphine: A Unique Drug with Complex Pharmacology

The prolactin-releasing peptide antagonizes the opioid system through its receptor GPR10

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