Opioid-modulating Peptides: Mechanisms of Action

Mollereau, Catherine; Roumy, M.; Zajac, Jean‐Marie

doi:10.2174/1568026053544515

Cited by 93 publications

(57 citation statements)

References 178 publications

(316 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…NGF, a neurotrophic factor known to be involved in animal models of peripheral inflammation (Lewin & Mendel, 1993), appears to play a modulatory role on morphine analgesia in the spinal cord LPS-induced CNS inflammation model. Cholecystokinin, a peptide known to possess anti-opioid effects (Cesselin, 1995;McLeane, 2004;Mollereau et al, 2005) also appears to be involved in the sensitivity to morphine of our CNS inflammation model. Increased spinal NGF with CNS inflammation is thought to decrease spinal CCK release, and this is suggested to explain enhanced spinal morphine sensitivity in this animal model.…”

Section: Discussionmentioning

confidence: 96%

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

et al. 2009

View full text Add to dashboard Cite

Animal models of inflammatory pain are characterized by the release of inflammatory mediators such as cytokines and neurotrophic factors, and enhanced analgesic sensitivity to opioids. In this study, we examine the mechanisms underlying this effect, in particular the roles of cholecystokinin (CCK) and nerve growth factor (NGF), in an animal model of central nervous system (CNS) inflammation induced by spinal administration of lipopolysaccharide (LPS). Although spinal administration of LY-225910 (25 ng), a CCK-B antagonist, enhanced morphine analgesia in naïve rats, it was unable to do so in LPS-treated animals. Conversely, spinal CCK-8S administration (1 ng) decreased morphine analgesia in LPS-treated rats, but not in naıve animals. Further, spinal anti-NGF (3 mg) was able to reduce morphine analgesia in LPS-treated rats, but not in naïve animals, an effect that was reversed by spinal administration of LY-225910. While CCK-8S concentration was increased in spinal cord extracts of LPS animals as compared to controls, morphine-induced spinal CCK release in the extracellular space, as measured by in-vivo spinal cord microdialysis was inhibited in LPS animals as compared to controls, and this was reversed by anti-NGF pretreatment. Finally, chronic spinal administration of b-NGF (7 mg/day) for 7 days enhanced spinal morphine analgesia, possibly by mimicking a CNS inflammatory state. We suggest that in intrathecally LPS-treated rats, spinal CCK release is altered resulting in enhanced morphine analgesia, and that this mechanism may be regulated to an important extent by NGF.

show abstract

Section: Discussionmentioning

confidence: 96%

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

et al. 2009

View full text Add to dashboard Cite

show abstract

“…These other opioid-modulating systems (also referred to as anti-opioid systems) include the neuropeptides CCK, NPFF, nociceptin and dynorphin, and their respective receptors. Although the biological actions of these various peptides are not identical, they have all been reported to counteract some of the main behavioral effects of morphine in laboratory animals, including analgesia, tolerance, reward and dependence 6 . It is now well accepted that these neuropeptidergic systems have a major role in the adaptive mechanisms that characterize the chronic stimulation of the opiate system: namely, tolerance and dependence.…”

Section: Discussionmentioning

confidence: 99%

“…In relation to the opiate system, NPFF and nociceptin show essentially the same panel of biological activities in vivo. Supraspinal administration of these peptides results in hyperalgesia, decrease of morphineand stress-induced analgesia, reduction of rewarding properties (only demonstrated for nociceptin), enhancement of tolerance of morphine and precipitation of morphine withdrawal (although a matter of conflict for nociceptin) 5,6,[26][27][28] . Spinal effects include analgesia and potentiation of morphine-induced analgesia 29 .…”

Section: Discussionmentioning

confidence: 99%

“…Other differences include the decrease in tolerance of morphine caused by dynorphin and the increase of rewarding effects of morphine caused by CCK, which contrasts with the action of the other anti-opioid peptides (reviewed in ref. 6). Also, knockout of the CCK 2 receptor gene led to spontaneous hyperalgesia and enhanced withdrawal signs 34 , which might be explained by an increase in central endogenous opioid peptide secretion with a paradoxical coupling of the m and d receptors.…”

Section: Discussionmentioning

confidence: 99%

“…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 .…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2005

View full text Add to dashboard Cite

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

Lipid‐Conjugation of Endogenous Neuropeptides: Improved Biotherapy against Human Pancreatic Cancer

Gopalakrishnan

Lepetre

Maksimenko

et al. 2015

Adv Healthcare Materials

View full text Add to dashboard Cite

Neuropeptides are small neuronal signaling molecules that act as neuromodulators for a variety of neural functions including analgesia, reproduction, social behavior, learning, and memory. One of the endogenous neuropeptides—Met-Enkephalin (Met-Enk), has been shown to display an inhibitory effect on cell proliferation and differentiation. Here, a novel lipid-modification approach is shown to create a small library of neuropeptides that will allow increased bioavailability and plasma stability after systemic administration. It is demonstrated, on an experimental model of human pancreatic adenocarcinoma, that lipid conjugation of Met-Enk enhances its tumor suppression efficacy compared to its nonlipidated counterparts, both in vitro and in vivo. More strikingly, the in vivo studies show that a combination therapy with a reduced concentration of Gemcitabine has suppressed the tumor growth considerably even three weeks after the last treatment.

show abstract

Opioid-modulating Peptides: Mechanisms of Action

Cited by 93 publications

References 178 publications

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

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

Lipid‐Conjugation of Endogenous Neuropeptides: Improved Biotherapy against Human Pancreatic Cancer

Contact Info

Product

Resources

About