Inhibitory action of nociceptin on spinal dorsal horn neurones of the rat, <i>in vivo</i>

Stanfa, Louise C.; Chapman, Victoria; Kerr, Nicola; Dickenson, Anthony H.

doi:10.1111/j.1476-5381.1996.tb15618.x

Cited by 126 publications

(51 citation statements)

References 8 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our finding that OFQ is antinociceptive in males is consistent with the evidence provided in previous electrophysiological and behavioral studies (Stanfa et al, 1996;Xu et al, 1996;Henderson and McKnight, 1997;Lai et al, 1997;Liebel et al, 1997;Meunier, 1997;Harrison and Grandy, 2000) (for review, see Mogil and Pasternak, 2001). Our data, however, as indicated above, indicate that this response of males is not simply attributable to the absence of estrogen but rather relies specifically on the availability of testosterone.…”

Section: Discussionsupporting

confidence: 92%

Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male

Claiborne¹,

Nag²,

Mokha³

2006

J. Neurosci.

View full text Add to dashboard Cite

Sex-related differences in the perception and modulation of pain have been reported. The present study is the first to investigate systematically whether activation of opioid receptor-like 1 receptor (ORL 1 ) by orphanin FQ (OFQ) produces sex-specific modulation of spinal nociception and whether estrogen or testosterone contributes to these differences using the rat as an experimental animal. Two behavioral models, the NMDA and heat-induced nociceptive tests, were used to examine sex-specific modulation of spinal nociception. Intrathecal microinjection of OFQ in male, ovariectomized (OVX), and diestrous rats produced a significant antinociceptive effect on both tests. However, OFQ failed to produce antinociception in proestrous rats, the phase of the estrous cycle with the highest levels of circulating estradiol, and produced a dose-dependent effect in OVX females treated with 1 ng to 100 g of estradiol. The antinociceptive effects of OFQ were dose dependent in male and OVX animals and were reversibly antagonized by UFP-101 ([Nphe 1 ,Arg ,Lys 15]N/ OFQ(1-13)-NH 2 ), an ORL 1 receptor-selective antagonist. Interestingly, OFQ was ineffective in gonadectomized (GDX) males, whereas testosterone replacement restored the antinociceptive effect of OFQ in GDX males. We conclude that OFQ produces sex-specific modulation of spinal nociception; estrogen attenuates antinociception in the female in parallel with normal cycling of estrogen levels, and testosterone is required for the expression of antinociception in the male; thus, the sensitivity of the male to the antinociceptive effects of OFQ is not simply attributable to the intrinsically low estrogen levels in these animals.

show abstract

Section: Discussionsupporting

confidence: 92%

Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male

Claiborne¹,

Nag²,

Mokha³

2006

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Nociceptin/orphanin FQ (N/OFQ), an endogenous peptide at the NOP receptor, inhibits cyclic AMP accumulation and Ca 2ϩ currents and increases K ϩ conductance in neurons, similar to the effects of agonists at the other opioid receptors (Meunier et al, 1995;Reinscheid et al, 1995;Jennings, 2001). These in vitro studies seem to support an inhibitory function of NOP receptor activation at sensory neurons (Stanfa et al, 1996;Helyes et al, 1997;Zeilhofer and Calo, 2003). Given that the actions of N/OFQ have much in common with those of opioid peptides at the cellular level, it is important to study behavioral effects of centrally administered N/OFQ.…”

mentioning

confidence: 88%

Effects of Intrathecally Administered Nociceptin/Orphanin FQ in Monkeys: Behavioral and Mass Spectrometric Studies

Ko¹,

Wei²,

Woods³

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Nociceptin/orphanin FQ (N/OFQ) is a heptadecapeptide that is an endogenous ligand for the N/OFQ peptide (NOP) receptor. The aim of this study was to investigate the behavioral responses of N/OFQ and its major fragment N/OFQ(2-17) in monkeys following i.t. administration. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used to quantify the amounts of N/OFQ and N/OFQ(2-17) in the cerebrospinal fluid at specific time points when effects of i.t. N/OFQ were sustained and disappeared. Intrathecal administration of N/OFQ dose dependently (10 -100 nmol) produced long-lasting antinociception against a noxious stimulus, 50°C water, and did not elicit itch/scratching responses in monkeys. Subcutaneous pretreatment with a selective NOP receptor antagonist, (ϩ)J-113397 [(1-[3R,4R)-1-cyclooctymethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3,-dihydro-2H-benzimidazol-2-one] (0.1 mg/kg), completely blocked i.t. N/OFQ (100 nmol)-induced antinociception. In contrast, a classic opioid receptor antagonist, naltrexone (0.01 and 1 mg/kg), failed to reverse i.t. N/OFQ-induced antinociception. MALDI-TOF-MS showed that the amount of N/OFQ(2-17) was 4-fold higher than that of N/OFQ at 1.5 h after i.t. administration of 100 nmol N/OFQ. Intrathecal N/OFQ-induced antinociception disappeared at 4.5 h, which corresponded to nearly undetectable cerebrospinal fluid levels of N/OFQ. No other metabolite of N/OFQ was detected at appreciable levels at either the 1.5-or 4.5-h time points. Although significant amounts of N/OFQ(2-17) were detected at the 1.5-and 4.5-h time points, 100 nmol N/OFQ(2-17) i.t. was inactive in changing the monkeys' nociceptive threshold. These results provide the first functional evidence of spinal N/OFQ-induced antinociception in primates and indicate that activation of spinal NOP receptors may be a potential target for spinal analgesics.The orphan opioid receptor has been identified in several species. It was previously called the ORL1 receptor and is now named the NOP receptor, as the fourth member within the opioid receptor family, by the International Union of Pharmacology (Mollereau et al., 1994;Foord et al., 2005). The sequence of the NOP receptor is closely related to each of the classical, well characterized -, ␦-, and -opioid receptors. However, ligands that bind to these classic opioid receptors do not bind NOP receptors with high affinity (Mollereau et al., 1994). The NOP receptor is widely distributed in the central nervous system, and it may participate in a broad range of behavioral and physiological functions (Neal et al., 1999a,b). Nociceptin/orphanin FQ (N/OFQ), an endogenous peptide at the NOP receptor, inhibits cyclic AMP accumulation and Ca 2ϩ currents and increases K ϩ conductance in neurons, similar to the effects of agonists at the other opioid receptors (Meunier et al., 1995;Reinscheid et al., 1995;Jennings, 2001). These in vitro studies seem to support an inhibitory function of NOP receptor activation at sensory neurons (Stanfa et al., 1996;Hel...

show abstract

“…Intrathecal injection of N/OFQ into the dorsal horn modulates C-fiber evoked "wind-up" and action potential discharge after repeated stimuli (Stanfa et al, 1996). In addition, N/OFQ suppresses glutamate ventral root potentials in a concentrationdependent manner (Faber et al, 1996), as well as depresses evoked-excitatory postsynaptic potentials (EPSPs) in the substantial gelatinosa neurons of the spinal cord.…”

Section: A Electrophysiological Analysis Of Nociceptin Opioid Peptidmentioning

confidence: 99%

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

et al. 2016

View full text Add to dashboard Cite

The NOP receptor (nociceptin/orphanin FQ opioid peptide receptor) is the most recently discovered member of the opioid receptor family and, together with its endogenous ligand, N/OFQ, make up the fourth members of the opioid receptor and opioid peptide family. Because of its more recent discovery, an understanding of the cellular and behavioral actions induced by NOP receptor activation are less well developed than for the other members of the opioid receptor family. All of these factors are important because NOP receptor activation has a clear modulatory role on mu opioid receptor-mediated actions and thereby affects opioid analgesia, tolerance development, and reward. In addition to opioid modulatory actions, NOP receptor activation has important effects on motor function and other physiologic processes. This review discusses how NOP pharmacology intersects, contrasts, and interacts with the mu opioid receptor in terms of tertiary structure and mechanism of receptor activation; location of receptors in the central nervous system; mechanisms of desensitization and downregulation; cellular actions; intracellular signal transduction pathways; and behavioral actions with respect to analgesia, tolerance, dependence, and reward. This is followed by a discussion of the agonists and antagonists that have most contributed to our current knowledge. Because NOP receptors are highly expressed in brain and spinal cord and NOP receptor activation sometimes synergizes with mu receptor-mediated actions and sometimes opposes them, an understanding of NOP receptor pharmacology in the context of these interactions with the opioid receptors will be crucial to the development of novel therapeutics that engage the NOP receptor

show abstract

Inhibitory action of nociceptin on spinal dorsal horn neurones of the rat, in vivo

Cited by 126 publications

References 8 publications

Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male

Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male

Effects of Intrathecally Administered Nociceptin/Orphanin FQ in Monkeys: Behavioral and Mass Spectrometric Studies

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

Contact Info

Product

Resources

About