Opioid Receptors Contribute to Antinociceptive Effect of Tianeptine on Colorectal Distension-Induced Visceral Pain in Rats

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 96-103 ◽  
Author(s):  
S. Sırrı Bilge ◽  
Fatih İlkaya ◽  
Özge Darakcı ◽  
Engin Çiftcioğlu ◽  
Ayhan Bozkurt
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Visceral Pain ◽  
Antinociceptive Effect ◽  
Colorectal Distension ◽  
Implanted Electrodes ◽  
Opioid Receptor Antagonist ◽  
Before And After ◽  
Peripheral Opioid Receptors

Tianeptine is a clinically effective atypical antidepressant with distinct neurochemical properties. In this study, we aimed to investigate the contribution of opioid receptors in the antinociceptive effect of tianeptine on visceral pain in awake rats and to differentiate the subtype and the localization (central and/or peripheral) of these opioid receptors involved in this antinociception. Visceromotor response to noxious colorectal distension (CRD) was quantified with electromyographic recordings, obtained from previously implanted electrodes into the external oblique musculature of rats under anesthesia, before and after tianeptine administration. The opioid receptor antagonist naloxone hydrochloride (NLX) and peripherally restricted opioid receptor antagonist naloxone methiodide (NLXM) were administered intravenously 10 min before tianeptine (10 mg/kg, i.v.). The antinociceptive effect of tianeptine was abolished by NLX (1 and 2 mg/kg, i.v.), but was partially reduced by NLXM (1 and 2 mg/kg, i.v.). A µ-opioid receptor-selective dose (0.03 mg/kg, i.v.) of NLX, but not NLXM, significantly inhibited the antinociceptive effect of tianeptine. Our results suggest that antinociceptive effect of tianeptine on CRD-induced visceral nociception in rats involves the activation of both central and peripheral opioid receptors.

kappa-Opioid antagonist improves cellular bioenergetics and recovery after traumatic brain injury

1991 ◽  
Vol 261 (6) ◽  
pp. R1527-R1532 ◽  
Author(s):  
R. Vink ◽  
P. S. Portoghese ◽  
A. I. Faden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Neurological Outcome ◽  
Kappa Opioid Receptors ◽  
Kappa Opioid ◽  
Opioid Receptor Antagonist ◽  
Cellular Bioenergetics

Treatment with opioid receptor antagonists improves outcome after experimental brain trauma, although the mechanisms underlying the protective actions of these compounds remain speculative. We have proposed that endogenous opioids contribute to the pathophysiology of traumatic brain injury through actions at kappa-opioid receptors, possibly by affecting cellular bioenergetic state. In the present study, the effects of the kappa-selective opioid-receptor antagonist nor-binaltorphimine (nor-BNI) were examined after fluid percussion brain injury in rats. Metabolic changes were evaluated by 31P magnetic resonance spectroscopy; the same animals were subsequently followed over 2 wk to evaluate neurological recovery. Nor-BNI, administered intravenously as a 10 or 20 mg/kg bolus at 30 min after injury, significantly improved neurological outcome at 2 wk posttrauma compared with controls. Animals treated with nor-BNI showed significantly greater recovery of intracellular free magnesium concentrations and cytosolic phosphorylation potentials during the first 4 h after injury compared with saline-treated controls. The improvement in cytosolic phosphorylation potential was significantly correlated to neurological outcome. These data support the hypothesis that kappa-opioid receptors mediate pathophysiological changes after traumatic brain injury and that the beneficial effects of opioid-receptor antagonist may result from improvement of posttraumatic cellular bioenergetics.

Protection of cardiac myocytes via δ1-opioid receptors, protein kinase C, and mitochondrial KATP channels

2001 ◽  
Vol 280 (1) ◽  
pp. H377-H383 ◽  
Author(s):  
Joon Huh ◽  
Garrett J. Gross ◽  
Hiroshi Nagase ◽  
Bruce T. Liang
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Receptor Antagonist ◽  
Cardiac Myocytes ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Inhibitory Effect ◽  
Cardioprotective Effect ◽  
Opioid Receptor Antagonist ◽  
Kinase C

The objective of the present study was to investigate the role of δ1-opioid receptors in mediating cardioprotection in isolated chick cardiac myocytes and to investigate whether protein kinase C and mitochondrial ATP-sensitive K+(KATP) channels act downstream of the δ1-opioid receptor in mediating this beneficial effect. A 5-min preexposure to the selective δ1-opioid receptor agonist (−)-TAN-67 (1 μM) resulted in less myocyte injury during the subsequent prolonged ischemia compared with untreated myocytes. 7-Benzylidenenaltrexone, a selective δ1-opioid receptor antagonist, completely blocked the cardioprotective effect of (−)-TAN-67. Naltriben methanesulfonate, a selective δ2-opioid receptor antagonist, had only a slight inhibitory effect on (−)-TAN-67-mediated cardioprotection. Nor-binaltorphimine dihydrochloride, a κ-opioid receptor antagonist, did not affect (−)-TAN-67-mediated cardioprotection. The protein kinase C inhibitor chelerythrine and the KATP channel inhibitors glibenclamide, a nonselective KATP antagonist, and 5-hydroxydecanoic acid, a mitochondrial selective KATPantagonist, reversed the cardioprotective effect of (−)-TAN-67. These results suggest that the δ1-opioid receptor is present on cardiac myocytes and mediates a potent cardioprotective effect via protein kinase C and the mitochondrial KATP channel.

scholarly journals Interactions of galanin with endomophin-2, vasopressin and oxytocin in nociceptive modulation of the trigemino-hypoglossal reflex in rats

2008 ◽  
pp. 769-776
Author(s):  
M Zubrzycka ◽  
A Janecka
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Antinociceptive Effect ◽  
Tooth Pulp ◽  
Cerebral Ventricles ◽  
Galanin Receptor ◽  
The Third ◽  
Opioid Receptor Antagonist ◽  
Pain Transmission ◽  
Δ Opioid Receptor

Galanin (GAL) is suggested to be a neuropeptide involved in pain transmission. In this study we tried to determine, whether the increase of GAL concentration in brain cells affects impulse transmission between the motor centers localized in the vicinity of the third and fourth cerebral ventricles. The experiments were carried out on rats under chloralose anesthesia. The study objectives were realized using the method allowing to record the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation during the perfusion of the cerebral ventricles with solutions containing tested compounds. Perfusion of the cerebral ventricles with GAL concentration-dependently inhibited the ETJ amplitude. The antinociceptive effect of GAL was blocked by a galanin receptor antagonist, galantide (GLT) and by opioid antagonists: non-selective naloxone (Nal) and μselective β-funaltrexamine (β-FNA). In contrast, a δ-opioid receptor antagonist, naltrindole (NTI) or the κ-opioid receptor antagonist, nor-binaltrophimine (nor-BNI) did not inhibit the effect of GAL. The antinociceptive effect of GAL was more pronounced when GAL was perfused in combination with other neuropeptides/neurohormones, such as endomorphin-2 (EM-2), vasopressin (AVP) and oxytocin (OT). The present results demonstrate that in the orofacial area analgesic activity is modulated by GAL, OT and AVP and that EM-2-induced antinociception involves GAL.

Synaptic Actions of Neuropeptide FF in the Rat Parabrachial Nucleus: Interactions With Opioid Receptors

2000 ◽  
Vol 84 (2) ◽  
pp. 744-751 ◽  
Author(s):  
Xihua Chen ◽  
Jeffrey A. Zidichouski ◽  
Kim H. Harris ◽  
Jack H. Jhamandas
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Distribution Curve ◽  
Parabrachial Nucleus ◽  
Synaptic Currents ◽  
Opioid Receptor Antagonist ◽  
Neuropeptide Ff ◽  
Δ Opioid Receptor ◽  
Synaptic Effects

The pontine parabrachial nucleus (PBN) receives both opioid and Neuropeptide FF (NPFF) projections from the lower brain stem and/or the spinal cord. Because of this anatomical convergence and previous evidence that NPFF displays both pro- and anti-opioid activities, this study examined the synaptic effects of NPFF in the PBN and the mechanisms underlying these effects using an in vitro brain slice preparation and the nystatin-perforated patch-clamp recording technique. Under voltage-clamp conditions, NPFF reversibly reduced the evoked excitatory postsynaptic currents (EPSCs) in a dose-dependent fashion. This effect was not accompanied by apparent changes in the holding current, the current-voltage relationship or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–induced inward currents in the PBN cells. When a paired-pulse protocol was used, NPFF increased the ratio of these synaptic currents. Analysis of miniature EPSCs showed that NPFF caused a rightward shift in the frequency-distribution curve, whereas the amplitude-distribution curve remained unchanged. Collectively, these experiments indicate that NPFF reduces the evoked EPSCs through a presynaptic mechanism of action. The synaptic effects induced by NPFF (5 μM) could not be blocked by the specific μ-opioid receptor antagonist,d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2(1 μM), but application of δ-opioid receptor antagonist Tyr-Tic-Phe-Phe (5 μM) almost completely prevented effects of NPFF. Moreover, the δ-opioid receptor agonist, Deltorphin (1 μM), mimicked the effects as NPFF and also occluded NPFF's actions on synaptic currents. These results indicate that NPFF modulates excitatory synaptic transmission in the PBN through an interaction with presynaptic δ-opioid receptors. These observations provide a cellular basis for NPFF enhancement of the antinociceptive effects consequent to central activation of δ-opioid receptors.

scholarly journals The Contribution of δ1- and δ2-Opioid Receptors to Hypoxia-Induced Pial Artery Dilation in the Newborn Pig

1995 ◽  
Vol 15 (3) ◽  
pp. 539-546 ◽  
Author(s):  
W. M. Armstead
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Receptor Activation ◽  
Severe Hypoxia ◽  
Moderate Hypoxia ◽  
Cranial Window ◽  
Pial Artery ◽  
Opioid Receptor Antagonist ◽  
Deltorphin Ii

Previously, it has been observed that μ-opioid receptors contribute to while κ-opioid receptors oppose pial artery dilation in response to hypoxia. The present study was designed to investigate the contribution of δ1- and δ2-opioid receptor activation to hypoxia-induced pial vasodilation. Newborn pigs equipped with a closed cranial window were used to measure pial artery diameter and collect cortical periarachnoid CSF for assay of opioids. Hypoxia increased CSF leucine enkephalin (a δ-agonist) from 36 ± 6 to 113 ± 17 pg/ml (n = 5). Hypoxiainduced pial artery vasodilation was attenuated during moderate hypoxia (Pao2 ≈ 35 mm Hg), while this response was blunted during severe hypoxia (Pao2 ≈ 25 mm Hg), by the δ1-opioid receptor antagonist 7-benzylidenenaltrexone (BNTX; 10−8 M) (23 ± 2 vs. 13 ± 2 and 34 ± 6 vs. 10 ± 3% for moderate and severe hypoxia in the absence and presence of BNTX, respectively; n = 5). In contrast, the δ2-opioid receptor antagonist naltrindole (10−9 M) blunted pial vasodilation during moderate hypoxia, but only attenuated the vasodilator response during severe hypoxia (22 ± 2 vs. 8 ± 2 and 33 ± 4 vs. 23 ± 4% for moderate and severe hypoxia in the absence and presence of naltrindole, respectively; n = 5). Receptor selectivity experiments show that BNTX blocked responses to the δ1-agonist DPDPE, whereas responses to the δ2-agonist deltorphin II were unchanged (12 ± 3 vs. 2 ± 1% and 14 ± 4 vs. 14 ± 3% for DPDPE at 10−6 M and deltorphin II at 10−6 M in the absence and presence of BNTX; n = 5). Similarly, naltrindole blocked responses to deltorphin II, but responses to DPDPE were unchanged. These data indicate that δ1-receptor activation contributes to both moderate and severe hypoxia-induced vasodilation, but the δ1-receptors appear to be more important during severe hypoxia relative to δ2-receptors. Additionally, these data show that δ2-receptors primarily contribute to dilation during moderate hypoxia.

scholarly journals Activation of δ-Opioid Receptors Reduces Excitatory Input to Putative Gustatory Cells Within the Nucleus of the Solitary Tract

2009 ◽  
Vol 101 (1) ◽  
pp. 258-268 ◽  
Author(s):  
Mingyan Zhu ◽  
Young K. Cho ◽  
Cheng-Shu Li
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Polymerase Chain Reaction Analysis ◽  
Excitatory Input ◽  
Solitary Tract ◽  
Opioid Receptor Antagonist ◽  
Naltrexone Hydrochloride ◽  
Parabrachial Nuclei ◽  
Δ Opioid Receptor

The rostral nucleus of the solitary tract (NST) is the first central relay in the gustatory pathway and plays a key role in processing and modulation of gustatory information. Here, we investigated the effects of opioid receptor agonists and antagonists on synaptic responses of the gustatory parabrachial nuclei (PbN)-projecting neurons in the rostral NST to electrical stimulation of the solitary tract (ST) using whole cell recordings in the hamster brain stem slices. ST-evoked excitatory postsynaptic currents (EPSCs) were significantly reduced by met-enkephalin (MetE) in a concentration-dependent fashion and this effect was eliminated by naltrexone hydrochloride, a nonselective opioid receptor antagonist. Bath application of naltrindole hydrochloride, a selective δ-opioid receptor antagonist, eliminated MetE-induced reduction of EPSCs, whereas CTOP, a selective μ-opioid receptor antagonist had no effect, indicating that δ-opioid receptors are involved in the reduction of ST-evoked EPSCs induced by MetE. SNC80, a selective δ-opioid receptor agonist, mimicked the effect of MetE. The SNC80-induced reduction of ST-evoked EPSCs was eliminated by 7-benzylidenenaltrexone, a selective δ1-opioid receptor antagonist but not by naltriben mesylate, a selective δ2-opioid receptor antagonist, indicating that δ1-opioid receptors mediate the reduction of ST-evoked EPSCs induced by SNC80. Single-cell reverse transcriptase–polymerase chain reaction analysis revealed the presence of δ1-opioid receptor mRNA in cells that responded to SNC80 with a reduction in ST-evoked EPSCs. Moreover, Western blot analysis demonstrated the presence of 40-kDa δ-opioid receptor proteins in the rostral NST tissue. These results suggest that postsynaptic δ1-opioid receptors are involved in opioid-induced reduction of ST-evoked EPSCs of PbN-projecting rostral NST cells.

scholarly journals Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Renata Cristina Mendes Ferreira ◽  
Ana Flávia Almeida-Santos ◽  
Igor Dimitri Gama Duarte ◽  
Daniele C. Aguiar ◽  
Fabricio A. Moreira ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Antinociceptive Effect ◽  
Opioid System ◽  
Prostaglandin E ◽  
Intraplantar Injection ◽  
Opioid Receptor Antagonist ◽  
Antinociceptive Effects ◽  
The Right

Background. Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect.Methods. Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2, 2 μg). Aripiprazole was injected 10 min before the measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and bestatin were given 30 min before aripiprazole. Nociceptive thresholds were measured in the 3rd hour after PGE2injection.Results. Aripiprazole (100 μg/paw) injected locally into the right hind paw induced an antinociceptive effect that was blocked by naloxone (50 μg/paw), a nonselective opioid receptor antagonist. The role ofμ-,δ-, andκ-opioid receptors was investigated using the selective antagonists, clocinnamox (40 μg/paw), naltrindole (15, 30, and 60 μg/paw), and nor-binaltorphimine (200 μg/paw), respectively. The data indicated that only theδ-opioid receptor antagonist inhibited the peripheral antinociception induced by aripiprazole. Bestatin (400 μg), an aminopeptidase-N inhibitor, significantly enhanced low-dose (25 μg/paw) aripiprazole-induced peripheral antinociception.Conclusion. The results suggest the participation of the opioid system viaδ-opioid receptor in the peripheral antinociceptive effect induced by aripiprazole.

scholarly journals Bulleyaconitine A Inhibits Visceral Nociception and Spinal Synaptic Plasticity through Stimulation of Microglial Release of Dynorphin A

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Sheng-Nan Huang ◽  
Jinbao Wei ◽  
Lan-Ting Huang ◽  
Pei-Jun Ju ◽  
Jinghong Chen ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Rat Model ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Trinitrobenzene Sulfonic Acid ◽  
Dependent Manner ◽  
Dynorphin A ◽  
Opioid Receptor Antagonist

Background. Visceral pain is one of the most common types of pain and particularly in the abdomen is associated with gastrointestinal diseases. Bulleyaconitine A (BAA), isolated from Aconitum bulleyanum, is prescribed in China to treat chronic pain. The present study is aimed at evaluating the mechanisms underlying BAA visceral antinociception. Methods. The rat model of chronic visceral hypersensitivity was set up by colonic perfusion of 2,4,6-trinitrobenzene sulfonic acid (TNBS) on postnatal day 10 with coapplication of heterotypic intermittent chronic stress (HeICS). Results. The rat model of chronic visceral hypersensitivity exhibited remarkable abdominal withdrawal responses and mechanical hyperalgesia in hind paws, which were dose-dependently attenuated by single subcutaneous of administration of BAA (30 and 90 μg/kg). Pretreatment with the microglial inhibitor minocycline, dynorphin A antiserum, and κ-opioid receptor antagonist totally blocked BAA-induced visceral antinociception and mechanical antihyperalgesia. Spontaneous excitatory postsynaptic currents (sEPSCs) in spinal dorsal horn lamina II neurons were recorded by using whole-cell patch clamp. Its frequency (but not amplitude) from TNBS-treated rats was remarkably higher than that from naïve rats. BAA (1 μM) significantly reduced the frequency of sEPSCs from TNBS-treated rats but not naïve rats. BAA-inhibited spinal synaptic plasticity was blocked by minocycline, the dynorphin A antiserum, and κ-opioid receptor antagonist. Dynorphin A also inhibited spinal synaptic plasticity in a κ-opioid receptor-dependent manner. Conclusions. These results suggest that BAA produces visceral antinociception by stimulating spinal microglial release of dynorphin A, which activates presynaptic κ-opioid receptors in afferent neurons and inhibits spinal synaptic plasticity, highlighting a novel interaction mode between microglia and neurons.

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