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Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats.
Eur J Pharmacol 2015; 754:73-81EJ

Abstract

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.

Authors+Show Affiliations

Department of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Florence, Italy.Department of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Florence, Italy. Electronic address: lorenzo.mannelli@unifi.it.Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, Ferrara, Italy.Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, Ferrara, Italy.Department of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Florence, Italy.School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Italy.Department of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Florence, Italy.Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25704616

Citation

Micheli, Laura, et al. "Acute and Subchronic Antinociceptive Effects of Nociceptin/orphanin FQ Receptor Agonists Infused By Intrathecal Route in Rats." European Journal of Pharmacology, vol. 754, 2015, pp. 73-81.
Micheli L, Di Cesare Mannelli L, Guerrini R, et al. Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats. Eur J Pharmacol. 2015;754:73-81.
Micheli, L., Di Cesare Mannelli, L., Guerrini, R., Trapella, C., Zanardelli, M., Ciccocioppo, R., ... Calò, G. (2015). Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats. European Journal of Pharmacology, 754, pp. 73-81. doi:10.1016/j.ejphar.2015.02.020.
Micheli L, et al. Acute and Subchronic Antinociceptive Effects of Nociceptin/orphanin FQ Receptor Agonists Infused By Intrathecal Route in Rats. Eur J Pharmacol. 2015 May 5;754:73-81. PubMed PMID: 25704616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acute and subchronic antinociceptive effects of nociceptin/orphanin FQ receptor agonists infused by intrathecal route in rats. AU - Micheli,Laura, AU - Di Cesare Mannelli,Lorenzo, AU - Guerrini,Remo, AU - Trapella,Claudio, AU - Zanardelli,Matteo, AU - Ciccocioppo,Roberto, AU - Rizzi,Anna, AU - Ghelardini,Carla, AU - Calò,Girolamo, Y1 - 2015/02/19/ PY - 2014/09/03/received PY - 2015/02/06/revised PY - 2015/02/11/accepted PY - 2015/2/24/entrez PY - 2015/2/24/pubmed PY - 2016/4/28/medline KW - Morphine KW - NOP receptor agonists KW - Nociceptin/orphanin FQ KW - Spinal analgesia KW - Tolerance SP - 73 EP - 81 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 754 N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/25704616/Acute_and_subchronic_antinociceptive_effects_of_nociceptin/orphanin_FQ_receptor_agonists_infused_by_intrathecal_route_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(15)00115-6 DB - PRIME DP - Unbound Medicine ER -