The nociceptin/orphanin FQ receptor system as a target to alleviate cancer-induced bone pain in rats: Model validation and pharmacological evaluation

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The nociceptin/orphanin FQ receptor system as a target to alleviate cancer-induced bone pain in rats : Model validation and pharmacological evaluation. / Sliepen, Sonny H J; Korioth, Johanna; Christoph, Thomas; Tzschentke, Thomas M; Diaz-delCastillo, Marta; Heegaard, Anne-Marie; Rutten, Kris.

In: British Journal of Pharmacology, 2020.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Sliepen, SHJ, Korioth, J, Christoph, T, Tzschentke, TM, Diaz-delCastillo, M, Heegaard, A-M & Rutten, K 2020, 'The nociceptin/orphanin FQ receptor system as a target to alleviate cancer-induced bone pain in rats: Model validation and pharmacological evaluation', British Journal of Pharmacology. https://doi.org/10.1111/bph.14899

APA

Sliepen, S. H. J., Korioth, J., Christoph, T., Tzschentke, T. M., Diaz-delCastillo, M., Heegaard, A-M., & Rutten, K. (2020). The nociceptin/orphanin FQ receptor system as a target to alleviate cancer-induced bone pain in rats: Model validation and pharmacological evaluation. British Journal of Pharmacology, [14899]. https://doi.org/10.1111/bph.14899

Vancouver

Sliepen SHJ, Korioth J, Christoph T, Tzschentke TM, Diaz-delCastillo M, Heegaard A-M et al. The nociceptin/orphanin FQ receptor system as a target to alleviate cancer-induced bone pain in rats: Model validation and pharmacological evaluation. British Journal of Pharmacology. 2020. 14899. https://doi.org/10.1111/bph.14899

Author

Sliepen, Sonny H J ; Korioth, Johanna ; Christoph, Thomas ; Tzschentke, Thomas M ; Diaz-delCastillo, Marta ; Heegaard, Anne-Marie ; Rutten, Kris. / The nociceptin/orphanin FQ receptor system as a target to alleviate cancer-induced bone pain in rats : Model validation and pharmacological evaluation. In: British Journal of Pharmacology. 2020.

Bibtex

@article{862edf6dd5a84759a546f6c6c27a68a0,
title = "The nociceptin/orphanin FQ receptor system as a target to alleviate cancer-induced bone pain in rats: Model validation and pharmacological evaluation",
abstract = "BACKGROUND AND PURPOSE: Cancer-induced bone pain remains inadequately controlled, and current standard of care analgesics is accompanied by several side effects. Nociceptin/orphanin FQ peptide (NOP) receptor agonists have demonstrated broad analgesic properties in rodent neuropathic and inflammatory pain models. Here, we investigate the analgesic potential of NOP receptor activation in a rodent cancer-induced bone pain model.EXPERIMENTAL APPROACH: Model validation by intratibial inoculation in male Sprague Dawley rats was performed with varying MRMT-1/Luc2 cell quantities (0.5-1.5 × 106 ·ml-1 ) and a behavioural battery (>14 days post-surgery) including evoked and non-evoked readouts: paw pressure test, cold plate, von Frey, open field, and weight distribution. Anti-allodynic potential of the endogenous NOP receptor ligand nociceptin (i.t.) and NOP receptor agonist Ro65-6570 ( i.p.) was tested using von Frey filaments, followed by a combination experiment with Ro65-6570 and the NOP receptor antagonist J-113397 (i.p.). Plasma cytokine levels and NOP receptor gene expression in dorsal root ganglion (DRG, L4-L6) and bone marrow were examined.KEY RESULTS: Inoculation with 1.5 × 106 ·ml-1 of MRMT-1/Luc2 cells resulted in a robust and progressive pain-related phenotype. Nociceptin and Ro65-6570 treatment inhibited cancer-induced mechanical allodynia. J-113397 selectively antagonized the effect of Ro65-6570. MRMT-1/Luc2-bearing animals demonstrated elevated plasma cytokine levels of IL-4, IL-5, IL-6 and IL-10 plus unaltered NOP-r gene expression in DRG and reduced expression in bone marrow.CONCLUSION AND IMPLICATIONS: Nociceptin and Ro65-6570 selectively and dose-dependently reversed cancer-induced bone pain-like behaviour. The NOP receptor system may be a potential target for cancer-induced bone pain treatment.",
author = "Sliepen, {Sonny H J} and Johanna Korioth and Thomas Christoph and Tzschentke, {Thomas M} and Marta Diaz-delCastillo and Anne-Marie Heegaard and Kris Rutten",
note = "{\circledC} 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.",
year = "2020",
doi = "10.1111/bph.14899",
language = "English",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley",

}

RIS

TY - JOUR

T1 - The nociceptin/orphanin FQ receptor system as a target to alleviate cancer-induced bone pain in rats

T2 - Model validation and pharmacological evaluation

AU - Sliepen, Sonny H J

AU - Korioth, Johanna

AU - Christoph, Thomas

AU - Tzschentke, Thomas M

AU - Diaz-delCastillo, Marta

AU - Heegaard, Anne-Marie

AU - Rutten, Kris

N1 - © 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

PY - 2020

Y1 - 2020

N2 - BACKGROUND AND PURPOSE: Cancer-induced bone pain remains inadequately controlled, and current standard of care analgesics is accompanied by several side effects. Nociceptin/orphanin FQ peptide (NOP) receptor agonists have demonstrated broad analgesic properties in rodent neuropathic and inflammatory pain models. Here, we investigate the analgesic potential of NOP receptor activation in a rodent cancer-induced bone pain model.EXPERIMENTAL APPROACH: Model validation by intratibial inoculation in male Sprague Dawley rats was performed with varying MRMT-1/Luc2 cell quantities (0.5-1.5 × 106 ·ml-1 ) and a behavioural battery (>14 days post-surgery) including evoked and non-evoked readouts: paw pressure test, cold plate, von Frey, open field, and weight distribution. Anti-allodynic potential of the endogenous NOP receptor ligand nociceptin (i.t.) and NOP receptor agonist Ro65-6570 ( i.p.) was tested using von Frey filaments, followed by a combination experiment with Ro65-6570 and the NOP receptor antagonist J-113397 (i.p.). Plasma cytokine levels and NOP receptor gene expression in dorsal root ganglion (DRG, L4-L6) and bone marrow were examined.KEY RESULTS: Inoculation with 1.5 × 106 ·ml-1 of MRMT-1/Luc2 cells resulted in a robust and progressive pain-related phenotype. Nociceptin and Ro65-6570 treatment inhibited cancer-induced mechanical allodynia. J-113397 selectively antagonized the effect of Ro65-6570. MRMT-1/Luc2-bearing animals demonstrated elevated plasma cytokine levels of IL-4, IL-5, IL-6 and IL-10 plus unaltered NOP-r gene expression in DRG and reduced expression in bone marrow.CONCLUSION AND IMPLICATIONS: Nociceptin and Ro65-6570 selectively and dose-dependently reversed cancer-induced bone pain-like behaviour. The NOP receptor system may be a potential target for cancer-induced bone pain treatment.

AB - BACKGROUND AND PURPOSE: Cancer-induced bone pain remains inadequately controlled, and current standard of care analgesics is accompanied by several side effects. Nociceptin/orphanin FQ peptide (NOP) receptor agonists have demonstrated broad analgesic properties in rodent neuropathic and inflammatory pain models. Here, we investigate the analgesic potential of NOP receptor activation in a rodent cancer-induced bone pain model.EXPERIMENTAL APPROACH: Model validation by intratibial inoculation in male Sprague Dawley rats was performed with varying MRMT-1/Luc2 cell quantities (0.5-1.5 × 106 ·ml-1 ) and a behavioural battery (>14 days post-surgery) including evoked and non-evoked readouts: paw pressure test, cold plate, von Frey, open field, and weight distribution. Anti-allodynic potential of the endogenous NOP receptor ligand nociceptin (i.t.) and NOP receptor agonist Ro65-6570 ( i.p.) was tested using von Frey filaments, followed by a combination experiment with Ro65-6570 and the NOP receptor antagonist J-113397 (i.p.). Plasma cytokine levels and NOP receptor gene expression in dorsal root ganglion (DRG, L4-L6) and bone marrow were examined.KEY RESULTS: Inoculation with 1.5 × 106 ·ml-1 of MRMT-1/Luc2 cells resulted in a robust and progressive pain-related phenotype. Nociceptin and Ro65-6570 treatment inhibited cancer-induced mechanical allodynia. J-113397 selectively antagonized the effect of Ro65-6570. MRMT-1/Luc2-bearing animals demonstrated elevated plasma cytokine levels of IL-4, IL-5, IL-6 and IL-10 plus unaltered NOP-r gene expression in DRG and reduced expression in bone marrow.CONCLUSION AND IMPLICATIONS: Nociceptin and Ro65-6570 selectively and dose-dependently reversed cancer-induced bone pain-like behaviour. The NOP receptor system may be a potential target for cancer-induced bone pain treatment.

U2 - 10.1111/bph.14899

DO - 10.1111/bph.14899

M3 - Journal article

C2 - 31724155

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

M1 - 14899

ER -

ID: 240984110