Supraspinal Actions of Nociceptin/orphanin FQ, Morphine and Substance P in Regulating Pain and Itch in Non-human Primates

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2015 Mar 11

PMID 25752320

Citations 30

Authors

H Ding

K Hayashida

T Suto

D D Sukhtankar

M Kimura

V Mendenhall

M C Ko

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects of centrally administered ligands on regulating pain and itch in non-human primates. In particular, nociceptive thresholds affected by intracisternal N/OFQ were compared with those of morphine and substance P, known to provide analgesia and mediate hyperalgesia, respectively, in humans.

Experimental Approach: Intrathecal catheters were installed to allow intracisternal and lumbar intrathecal administration in awake and unanaesthetized rhesus monkeys. Nociceptive responses were measured using the warm water tail-withdrawal assay. Itch scratching responses were scored from videotapes recording behavioural activities of monkeys in their home cages. Antagonist studies were conducted to validate the receptor mechanisms underlying intracisternally elicited behavioural responses.

Key Results: Intracisternal morphine (100 nmol) elicited more head scratches than those after intrathecal morphine. Distinct dermatomal scratching locations between the two routes suggest a corresponding activation of supraspinal and spinal μ receptors. Unlike intracisternal substance P, which induced hyperalgesia, intracisternal N/OFQ (100 nmol) produced antinociceptive effects mediated by NOP receptors. Neither peptide increased scratching responses.

Conclusions And Implications: Taken together, these results demonstrated differential actions of ligands in the primate supraspinal region in regulating pain and itch. This study not only improves scientific understanding of the N/OFQ-NOP receptor system in pain processing but also supports the therapeutic potential of NOP-related ligands as analgesics.

Citing Articles

Nociceptin Receptor-Related Agonists as Safe and Non-addictive Analgesics.

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Potential therapeutic targets for the treatment of opioid abuse and pain.

Kiguchi N, Ko M Adv Pharmacol. 2022; 93:335-371.

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Functional roles of neuromedin B and gastrin-releasing peptide in regulating itch and pain in the spinal cord of non-human primates.

Kiguchi N, Ding H, Park S, Mabry K, Kishioka S, Shiozawa Y Biochem Pharmacol. 2022; 198:114972.

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MOP and NOP receptor interaction: Studies with a dual expression system and bivalent peptide ligands.

Bird M, McDonald J, Horley B, ODoherty J, Fraser B, Gibson C PLoS One. 2022; 17(1):e0260880.

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