Spinal   and   Opioids Inhibit Both Thermal and Mechanical Pain in Rats

Normandin, Audrey; Luccarini, Philippe; Molat, Jean‐Louis; Gendron, Louis; Dallel, Radhouane

doi:10.1523/jneurosci.1631-13.2013

Cited by 32 publications

(34 citation statements)

References 84 publications

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“…Finally, an insufficient population of DOPrs is present in substance P-containing neurons to produce a physiologic effect (Bardoni et al, 2014). Nevertheless, DOPr immunoreactivity was identified in substance P neurons within the myenteric plexus of the small intestine of DOPr-eGFP knock-in mice (Poole et al, 2011), demonstrating that DOPrs can be coexpressed with substance P. Moreover, DOPr activation also inhibits substance P release from primary afferents (Beaudry et al, 2011;Kouchek et al, 2013;Normandin et al, 2013). The dispute over whether DOPrs are present in substance P-containing neurons remains unresolved, because in situ hybridization and single-cell polymerase chain reaction studies report different results Wang et al, 2010).…”

Section: D-opioid Receptor Pharmacologymentioning

confidence: 99%

Molecular Pharmacology ofδ-Opioid Receptors

et al. 2016

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Section: D-opioid Receptor Pharmacologymentioning

confidence: 99%

Molecular Pharmacology ofδ-Opioid Receptors

et al. 2016

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“…Recent studies have shown that both thermal and mechanical hyperalgesia are inhibited by either δ‐ or μ‐opioid receptor agonists through the activation of δ‐ or μ‐opioid receptors, respectively, in nociceptive afferents (Joseph and Levine, ; Gaveriaux‐Ruff et al ., ; He et al ., ; Kim et al ., ; Normandin et al ., ). These results are consistent with the coexistence of δ‐ and μ‐opioid receptors in peptidergic small DRG neurons, and support the notion that δ‐ and μ‐opioid receptors interact in the nociceptive sensory circuit.…”

Section: Role Of Opioid Receptor Interaction In Morphine Antinociceptmentioning

confidence: 97%

“…Early autoradiographic studies showed that many opioid receptors and the binding sites for μ‐ and δ‐opioid receptor agonists, are present in nociceptive afferent Aδ‐ and C‐fibres terminating in the superficial dorsal horn of the spinal cord (Fields et al ., ; Moskowitz and Goodman, ; Gouarderes et al ., ; Besse et al ., ; Mennicken et al ., ). Moreover, the release of the excitatory neurotransmitter glutamate, the neuropeptides substance P and CGRP from afferent C‐ and Aδ‐fibres could be inhibited by activating δ‐opioid receptors with several δ‐opioid receptor agonists (Ueda et al ., ; Zachariou and Goldstein, ; Beaudry et al ., ; Normandin et al ., ), suggesting the presynaptic localization of δ‐opioid receptors on nociceptive afferents. This notion was supported by the finding that δ‐opioid receptor mRNA is present in about 70% of DRG neurons, including both peptidergic [isolectin B4 (IB4)‐negative] and non‐peptidergic (IB4‐positive) subsets of small neurons and mechanoreceptive large neurons, while μ‐opioid receptors were expressed in the subsets of small DRG neurons and some large DRG neurons (Arvidsson et al ., ; Minami et al ., ; Wang and Wessendorf, ; Wang et al ., ; Gaveriaux‐Ruff et al ., ; He et al ., ).…”

Section: Co‐expression Of Opioid Receptors In Nociceptive Afferent Nementioning

confidence: 99%

“…The co‐expression of δ‐ and μ‐opioid receptors in peptidergic small DRG neurons is also supported by the finding that both of these receptors mediated inhibitory effects on the Ca 2+ currents in the same small DRG neurons and the release of substance P from C‐ and Aδ‐afferents (Arvidsson et al ., 1995a,b; Ji et al ., ; Zachariou and Goldstein, ; Zhang et al ., 1998a,b; Wu et al ., ; Guan et al ., ; Rau et al ., ; Walwyn et al ., ; Beaudry et al ., ; Kouchek et al ., ; Normandin et al ., ). Taken together, these results suggest that the co‐expression of δ‐ and μ‐opioid receptors in certain populations of small DRG neurons is the cellular basis for opioid receptor interactions in the pain pathway.…”

Section: Co‐expression Of Opioid Receptors In Nociceptive Afferent Nementioning

confidence: 99%

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Opioid receptor trafficking and interaction in nociceptors

Zhang¹,

Liu

2014

British J Pharmacology

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Opiate analgesics such as morphine are often used for pain therapy. However, antinociceptive tolerance and dependence may develop with long-term use of these drugs. It was found that μ-opioid receptors can interact with δ-opioid receptors, and morphine antinociceptive tolerance can be reduced by blocking δ-opioid receptors. Recent studies have shown that μ-and δ-opioid receptors are co-expressed in a considerable number of small neurons in the dorsal root ganglion. The interaction of μ-opioid receptors with δ-opioid receptors in the nociceptive afferents is facilitated by the stimulus-induced cell-surface expression of δ-opioid receptors, and contributes to morphine tolerance. Further analysis of the molecular, cellular and neural circuit mechanisms that regulate the trafficking and interaction of opioid receptors and related signalling molecules in the pain pathway would help to elucidate the mechanism of opiate analgesia and improve pain therapy. LINKED ARTICLESThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 Abbreviations CGRP, calcitonin gene-related peptide; DOPr-eGFP, δ-opioid receptors inserted with the enhanced green fluorescent protein at the C-terminus; DAMGO, Tyr-D-Ala-Gly-MePhe-Gly-ol; DRG, dorsal root ganglion; HA, haemagglutinin; IB4, isolectin B4; LDCV, large dense-core vesicle; PC12 cell, phaeochromocytoma cell; PM, plasma membrane BackgroundMorphine is widely used for pain therapy. However, its clinical applications are often limited by the development of antinociceptive tolerance. That is, when a dose of morphine is given repeatedly and selectively for a single condition, it gradually loses its antinociceptive potency (Fields, 2004;Manchikanti and Singh, 2008). Studies over the past few decades have demonstrated the presence of many types of opioid receptor in the nociceptive sensory neurons and their Aδ-and C-fibre terminals in the superficial dorsal horn of the spinal cord (Fields et al., 1980; Moskowitz and Goodman, 1984;Gouarderes et al., 1991;Besse et al., 1992;Mennicken et al., 2003). The μ-and δ-opioid receptors are predominantly found to be expressed in small-diameter neurons of the dorsal root ganglion (DRG). These small DRG neurons convey the signals from peripheral nociceptors, thermoreceptors and sensitive mechanoreceptors to the superficial dorsal horn of spinal cord, and cause the release of the excitatory neurotransmitter glutamate, as well as the neuropeptides substance P and calcitonin gene-related peptide (CGRP), from the afferent terminals. This excitatory neurotransmission can be presynaptically inhibited by activating μ-or δ-opioid receptors (Ueda et al., 1995;Zachariou and Goldstein, 1996;Beaudry et al., 2011). Therefore, it is of interest to explore the molecular and cellular mechanisms that regulate opioid analgesia and tolerance. The present review discusses the expression, intracellular trafficking and interaction of opioid recept...

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“…Specifically, stimulation of both spinal and peripheral -, ␦-, and -opioid receptors has been shown to exert potent antinociceptive effects in a variety of pain models (15,23,24,26). Our laboratory has demonstrated recently that stimulation of -opioid and ␦-opioid receptors located on the peripheral endings of hindlimb muscle afferents attenuated the exaggerated exercise pressor reflex in rats with ligated femoral arteries (17, 37).…”

mentioning

confidence: 99%

Effects of peripheral and spinal κ-opioid receptor stimulation on the exercise pressor reflex in decerebrate rats

Copp

Stone

Yamauchi

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Copp SW, Stone AJ, Yamauchi K, Kaufman MP. Effects of peripheral and spinal -opioid receptor stimulation on the exercise pressor reflex in decerebrate rats. Am J Physiol Regul Integr Comp Physiol 307: R281-R289, 2014. First published June 11, 2014 doi:10.1152/ajpregu.00156.2014The exercise pressor reflex is greater in rats with ligated femoral arteries than it is in rats with freely perfused femoral arteries. The exaggerated reflex in rats with ligated arteries is attenuated by stimulation of -opioid and ␦-opioid receptors on the peripheral endings of thin-fiber muscle afferents. The effect of stimulation of -opioid receptors on the exercise pressor reflex is unknown. We tested the hypothesis that stimulation of -opioid receptors attenuates the exercise pressor reflex in rats with ligated, but not freely perfused, femoral arteries. The pressor responses to static contraction were compared before and after femoral arterial or intrathecal injection of the -opioid receptor agonist U62066 (1, 10, and 100 g). Femoral arterial injection of U62066 did not attenuate the pressor responses to contraction in either group of rats. Likewise, intrathecal injection of U62066 did not attenuate the pressor response to contraction in rats with freely perfused femoral arteries. In contrast, intrathecal injection of 10 and 100 g of U62066 attenuated the pressor response to contraction in rats with ligated femoral arteries, an effect that was blocked by prior intrathecal injection of the -opioid receptor antagonist nor-binaltorphimine. In rats with ligated femoral arteries, the pressor response to stimulation of peripheral chemoreceptors by sodium cyanide was not changed by intrathecal U62066 injections, indicating that these injections had no direct effect on the sympathetic outflow. We conclude that stimulation of spinal, but not peripheral, -opioid receptors attenuates the exaggerated exercise pressor reflex in rats with ligated femoral arteries. skeletal muscle afferents; exercise; peripheral artery disease; spiradoline ACTIVATION OF THE EXERCISE pressor reflex is responsible, at least in part, for the cardiovascular and ventilatory adjustments to exercise (13). The afferent arm of the reflex comprises group III and IV muscle afferents, which respond predominantly to mechanical and metabolic stimuli, respectively (14,19). Group III and IV afferents, which together are termed thin-fiber afferents, synapse onto interneurons in the dorsal horn of the spinal cord (10). These interneurons, in turn, project initially to neurons in the ventrolateral medulla and the nucleus of the solitary tract (9, 29), and eventually to autonomic preganglionic neurons. The functional consequences of activating the exercise pressor reflex during exercise include increases in arterial blood pressure, heart rate (HR), and ventilation, all of which contribute to the increases in exercising skeletal muscle blood flow and O 2 delivery (1, 2, 27).In cats, dogs, and rats, acute or chronic muscle ischemia exaggerates the exercise pressor reflex (8,19,27,32,3...

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Spinal and Opioids Inhibit Both Thermal and Mechanical Pain in Rats

Cited by 32 publications

References 84 publications

Molecular Pharmacology ofδ-Opioid Receptors

Molecular Pharmacology ofδ-Opioid Receptors

Opioid receptor trafficking and interaction in nociceptors

Effects of peripheral and spinal κ-opioid receptor stimulation on the exercise pressor reflex in decerebrate rats

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