Endogenous nociceptin signaling and stress-induced analgesia

Abstract

Nociceptin/orphanin FQ (NC) and its receptor (OP4) have been implicated in pain transmission. The aim of the present study was to investigate the role of the NC/OP4 system in stress-induced analgesia (SIA). The tail-withdrawal assay was performed in mice stressed by forced swimming in water at 15 degrees C (high severity swims) or 32 degrees C (low severity swims). High severity swims produced a naloxone-insensitive antinociceptive effect which was blocked by supraspinal NC (1 nmol). The selective OP4 receptor antagonist, [Nphe1]NC(-13)NH2 (30 nmol), was inactive by itself, but prevented the effect of NC. Low severity swims produced a milder analgesic effect that was partially antagonized by naloxone, completely blocked by NC and potentiated by [Nphe1]NC(-13)NH2. These findings confirm the anti-analgesic role of supraspinal NC and suggest that endogenous NC signaling counteracts the opioid component of SIA.

Differential Activation of the Periaqueductal Gray by Mild Anxiogenic Stress at Different Stages of the Estrous Cycle in Female Rats

“…These findings suggest that there may be two functionally distinct pro-and antinociceptive descending pathways from the ventrolateral orbitofrontal cortex to the PAG, which may be activated differentially according to the way the stimulus is perceived by the individual. In support of this idea, studies in male rats have shown that although exposure to a non-noxious stress induced hyperalgesia (Vidal and Jacob, 1982;J rum, 1988), a more severe stress induced an increase in pain threshold (Rizzi et al, 2001;Vendruscolo et al, 2004). The mild stressor used in this study would therefore be expected to activate the pro-nociceptive pathways from the PAG.…”

Central injections of nocistatin or its C‐terminal hexapeptide exert anxiogenic‐like effect on behaviour of mice in the plus‐maze test

“…Analgesia induced by morphine or stress in mice, or by electro-acupuncture in rats, is potentiated by i.c.v. injections of either the highly selective NOP receptor antagonist [Nphe 1 ]nociceptin(1-13)NH 2 2001b) or of an antibody against N/OFQ (Tian & Han, 2000), respectively. On the other hand, i.t.…”

Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia

“…N/OFQ administered centrally can completely block severe SIA (16). In contrast to Hcrt, N/OFQ cell bodies are widely distributed throughout the CNS (17).…”

“…Nociceptin (N/OFQ; also known as orphanin FQ) (13,14) is a neuropeptide that has also been implicated in a number of physiological functions including locomotion, feeding behavior, anxiety, memory, pain, and stress responses, particularly SIA (15,16). N/OFQ administered centrally can completely block severe SIA (16).…”

“…N/OFQ is known to inhibit SIA (16), although the neuronal pathways that mediate N/OFQ effects on SIA are still poorly understood. Since N/OFQ inhibits SIA and Hcrt appears to be necessary for SIA (Figure 7, B and C), we hypothesized that acute suppression of Hcrt signaling was the mechanism by which N/OFQ inhibited SIA and, therefore, i.c.v.…”