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

Sonny H J Sliepen1,2, Johanna Korioth1, Thomas Christoph1

  • 1Grünenthal Innovation, Grünenthal GmbH, Aachen, Germany.

British Journal of Pharmacology
|November 15, 2019
PubMed
Abstract

Insights

Nociceptin/orphanin FQ peptide (NOP) receptor agonists effectively reversed cancer-induced bone pain in a rodent model. This suggests the NOP receptor system is a promising therapeutic target for managing bone pain associated with cancer.

Area of Science:

  • Pharmacology
  • Pain Research
  • Oncology

Background:

  • Cancer-induced bone pain is a significant clinical challenge with limited effective treatments.
  • Current analgesics often cause severe side effects.
  • Nociceptin/orphanin FQ peptide (NOP) receptor agonists show promise for pain management.

Purpose of the Study:

  • To investigate the analgesic potential of NOP receptor activation in a rodent model of cancer-induced bone pain.
  • To validate a rat model of cancer-induced bone pain.
  • To assess the efficacy of NOP receptor agonists and antagonists.

Main Methods:

  • A cancer-induced bone pain model was established in rats using MRMT-1/Luc2 cell inoculation.
  • Behavioral tests (paw pressure, cold plate, von Frey, open field, weight distribution) were used to assess pain phenotypes.
  • The effects of nociceptin and the NOP receptor agonist Ro65-6570 were evaluated, along with the antagonist J-113397.
  • Plasma cytokine levels and NOP receptor gene expression in the dorsal root ganglion and bone marrow were analyzed.

Main Results:

  • MRMT-1/Luc2 cell inoculation induced a progressive pain phenotype in rats.
  • Nociceptin and Ro65-6570 significantly inhibited cancer-induced mechanical allodynia.
  • The NOP receptor antagonist J-113397 selectively blocked the analgesic effects of Ro65-6570.
  • Elevated plasma levels of IL-4, IL-5, IL-6, and IL-10 were observed in tumor-bearing animals.

Conclusions:

  • NOP receptor activation, via nociceptin or Ro65-6570, selectively reversed cancer-induced bone pain behaviors.
  • The NOP receptor system represents a potential therapeutic target for treating cancer-induced bone pain.
  • Further research into NOP receptor modulation could lead to novel pain management strategies.

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