IgG from neuropeptide FF antiserum reverses morphine tolerance in the rat

Lake, John R.; Hammond, Maria V.; Shaddox, Robert C.; Hunsicker, Lisa M.; Yang, Hsui-Ying T.; Malin, David H.

doi:10.1016/0304-3940(91)90425-s

Cited by 107 publications

(34 citation statements)

References 13 publications

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“…The ability of AC-262616 to significantly decrease baseline sensory thresholds suggests the possibility that FF1 receptor activation, in addition to promoting morphine antinociceptive tolerance, may also contribute to opioid-induced paradoxical pain. This idea is supported by the observation that intracerebroventricular administration of an anti-NPFF antiserum completely restores the efficacy of intracerebroventricular morphine in tolerant rats (Lake et al, 1991). In addition, administration of a pan FF1/FF2 receptor antagonist, RF9, prevents heroin-induced hyperalgesia and effectively blocks the development of antinociceptive tolerance after repeated heroin treatment (Simonin et al, 2006).…”

Section: Discussionmentioning

confidence: 91%

Neuropeptide FF Receptors Have Opposing Modulatory Effects on Nociception

Lameh

Bertozzi²,

Kelly³

et al. 2010

J Pharmacol Exp Ther

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The role of neuropeptide FF (NPFF) and its analogs in pain modulation is ambiguous. Although NPFF was first characterized as an antiopioid peptide, both antinociceptive and pronociceptive effects have been reported, depending on the route of administration. Currently, two NPFF receptors, termed FF1 and FF2, have been identified and cloned, but their roles in pain modulation remain elusive because of the lack of availability of selective compounds suitable for systemic administration in in vivo models. Ligand-binding studies confirm ubiquitous expression of both subtypes in brain, whereas only FF2 receptors are expressed spinally. This disparity in localization has served as the foundation of the hypothesis that FF1 receptors mediate the pronociceptive actions of NPFF. We have identified novel small molecule NPFF receptor agonists and antagonists with varying degrees of FF2/FF1 functional selectivity. Using these pharmacological tools in vivo has allowed us to define the roles of NPFF receptor subtypes as pertains to the modulation of nociception. We demonstrate that selective FF2 agonism does not modulate acute pain but instead ameliorates inflammatory and neuropathic pains. Treatment with a nonselective FF1/FF2 agonist potentiates allodynia in neuropathic rats and increases sensitivity to noxious thermal and to non-noxious mechanical stimuli in normal rats in an FF1 antagonist-reversible manner. Treatment with FF1 antagonists reversed established mechanical allodynia, indicating the possibility of increased NPFF tone through FF1 receptors. In conclusion, we provide evidence for the opposing roles of NPFF receptors and highlight selective FF2 agonism and/or selective FF1 antagonism as potential targets warranting further investigation.

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Section: Discussionmentioning

confidence: 91%

Neuropeptide FF Receptors Have Opposing Modulatory Effects on Nociception

Lameh

Bertozzi²,

Kelly³

et al. 2010

J Pharmacol Exp Ther

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“…Intracerebroventricular administration of FMRFamide, NPFF, or NPAF attenuated morphine-induced analgesia whereas injection of antisera against FMRFamide or NPFF had the opposite effect (5,10). Administration of NPFF into morphine-tolerant rats induced symptoms of the withdrawal whereas administration of anti-NPFF IgG reversed morphine tolerance (11,12). Such observations led to the classification of NPFF as one type of anti-opioid peptides, which have been hypothesized to be partially responsible for the rapid development of opioid tolerance and dependence in animal models and clinical use of opioids (13).…”

mentioning

confidence: 99%

Identification and Characterization of Novel Mammalian Neuropeptide FF-like Peptides That Attenuate Morphine-induced Antinociception

Liu

Guan²,

Martin

et al. 2001

Journal of Biological Chemistry

245

301

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The two mammalian neuropeptides NPFF and NPAF have been shown to have important roles in nociception, anxiety, learning and memory, and cardiovascular reflex. Two receptors (FF1 and FF2) have been molecularly identified for NPFF and NPAF. We have now characterized a novel gene designated NPVF that encodes two neuropeptides highly similar to NPFF. NPVF mRNA was detected specifically in a region between the dorsomedial and ventromedial hypothalamic nuclei. NPVFderived peptides displayed higher affinity for FF1 than NPFF-derived peptides, but showed poor agonist activity for FF2. Following intracerebral ventricular administration, a NPVF-derived peptide blocked morphineinduced analgesia more potently than NPFF in both acute and inflammatory models of pain. In situ hybridization analysis revealed distinct expression patterns of FF1 and FF2 in the rat central nervous system. FF1 was broadly distributed, with the highest levels found in specific regions of the limbic system and the brainstem where NPVF-producing neurons were shown to project. FF2, in contrast, was mostly expressed in the spinal cord and some regions of the thalamus. These results indicate that the endogenous ligands for FF1 and FF2 are NPVFand NPFF-derived peptides, respectively, and suggest that the NPVF/FF1 system may be an important part of endogenous anti-opioid mechanism.

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“…Other research groups have shown that antisera to endogenous compounds can be used to interfere with the actions of endogenous compounds in in vivo models of opioid tolerance and analgesia, including neuropeptide FF (Lake et al, 1991), Leu-and Met-enkephalin (Vanderah et al, 1994;Tseng et al, 2000;Ohsawa et al, 2001), ␤-endorphin (Tseng et al, 2000;Ohsawa et al, 2001), and dynorphin (Ossipov et al, 1996;Tseng et al, 2000;Ohsawa et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

Immunoneutralization of Agmatine Sensitizes Mice to μ-Opioid Receptor Tolerance

Wade

Eskridge

Nguyen

et al. 2009

J Pharmacol Exp Ther

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Systemically or centrally administered agmatine (decarboxylated arginine) prevents, moderates, or reverses opioid-induced tolerance and self-administration, inflammatory and neuropathic pain, and sequelae associated with ischemia and spinal cord injury in rodents. These behavioral models invoke the N-methyl-D-aspartate (NMDA) receptor/nitric-oxide synthase cascade. Agmatine (AG) antagonizes the NMDA receptor and inhibits nitric-oxide synthase in vitro and in vivo, which may explain its effect in models of neural plasticity. Agmatine has been detected biochemically and immunohistochemically in the central nervous system. Consequently, it is conceivable that agmatine operates in an anti-glutamatergic manner in vivo; the role of endogenous agmatine in the central nervous system remains minimally defined. The current study used an immunoneutralization strategy to evaluate the effect of sequestration of endogenous agmatine in acute opioid analgesic tolerance in mice. First, intrathecal pretreatment with an anti-AG IgG (but not normal IgG) reversed an established pharmacological effect of intrathecal agmatine: antagonism of NMDA-evoked behavior. This result justified the use of anti-AG IgG to sequester endogenous agmatine in vivo. Second, intrathecal pretreatment with the anti-AG IgG sensitized mice to induction of acute spinal tolerance of two -opioid receptor-selective agonists, [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]-enkephalin and endomorphin-2. A lower dose of either agonist that, under normal conditions, produces moderate or no tolerance was tolerance-inducing after intrathecal pretreatment of anti-AG IgG (but not normal IgG). The effect of the anti-AG IgG lasted for at least 24 h in both NMDA-evoked behavior and the acute opioid tolerance. These results suggest that endogenous spinal agmatine may moderate glutamate-dependent neuroplasticity.

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IgG from neuropeptide FF antiserum reverses morphine tolerance in the rat

Cited by 107 publications

References 13 publications

Neuropeptide FF Receptors Have Opposing Modulatory Effects on Nociception

Neuropeptide FF Receptors Have Opposing Modulatory Effects on Nociception

Identification and Characterization of Novel Mammalian Neuropeptide FF-like Peptides That Attenuate Morphine-induced Antinociception

Immunoneutralization of Agmatine Sensitizes Mice to μ-Opioid Receptor Tolerance

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