RGD Reference Report - Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats. - Rat Genome Database

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Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats.

Authors: Micheli, Laura  Di Cesare Mannelli, Lorenzo  Guerrini, Remo  Trapella, Claudio  Zanardelli, Matteo  Ciccocioppo, Roberto  Rizzi, Anna  Ghelardini, Carla  Calò, Girolamo 
Citation: Micheli L, etal., Eur J Pharmacol. 2015 May 5;754:73-81. doi: 10.1016/j.ejphar.2015.02.020. Epub 2015 Feb 19.
RGD ID: 14349028
Pubmed: PMID:25704616   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ejphar.2015.02.020   (Journal Full-text)

Severe pain occurs in the context of many diseases and conditions and is a leading cause of disability. Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of the N/OFQ peptide (NOP) receptor. This peptidergic system controls pain transmission and in particular spinally administered N/OFQ has robust antinociceptive properties. The aim of this study was to investigate the spinal antinociceptive properties of NOP peptide agonists after acute and subchronic treatment in rats. Doses unable to alter motor coordination were selected. UFP-112 (full NOP agonist) and UFP-113 (partial NOP agonist) were administered intrathecally (i.t.) by spinal catheterization. Acute injection of UFP-112 induced antinociceptive response at lower dosages (0.03-1nmol i.t.) compared to morphine and similar to N/OFQ. UFP-113 was effective in a 0.001-1nmol i.t. dose range. The antinociceptive effects of NOP ligands were no longer evident in rats knockout for the NOP gene, while those of morphine were maintained. The continuous spinal infusion (by osmotic pumps) of 0.1nmol/h UFP-112 and UFP-113 showed antinociceptive action comparable to 1-3nmol/h morphine or N/OFQ. The antinociceptive effect of morphine progressively decreased and was no longer significant after 6 days of treatment. Similar results were obtained with N/OFQ, UFP-112, and UFP-113. The acute i.t. injection of morphine in animals tolerant to N/OFQ and UFP-112 evoked analgesic effects. Neither morphine nor N/OFQ induced antinociceptive effects in morphine- and UFP-113-tolerant rats. In conclusion this study highlights the analgesic efficacy and potency of UFP-112 and UFP-113 underlining the relevance of NOP system in analgesia.

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased mechanical nociceptive threshold  IMP 14349028; 14349028 RGD 
decreased mechanical nociceptive threshold inducedIMPmorphine14349028 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Oprl1  (opioid related nociceptin receptor 1)
Oprl1m1Hubr  (opioid related nociceptin receptor 1; ENU induced mutant1, Hubr)

Strains
WI-Oprl1m1Hubr-/-  (NOPr knockout rat)


Additional Information