The nociceptin/orphanin FQ receptor system as a target to alleviate cancer-induced bone pain in rats: Model validation and pharmacological evaluation
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- bph.14899 (1)
Forlagets udgivne version, 1,2 MB, PDF-dokument
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.
Originalsprog | Engelsk |
---|---|
Artikelnummer | 14899 |
Tidsskrift | British Journal of Pharmacology |
Vol/bind | 178 |
Udgave nummer | 9 |
Sider (fra-til) | 1995-2007 |
Antal sider | 13 |
ISSN | 0007-1188 |
DOI | |
Status | Udgivet - 2021 |
Bibliografisk note
© 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 240984110