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Wiliam A Prado - One of the best experts on this subject based on the ideXlab platform.
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the lesion of dorsolateral funiculus changes the antiallodynic effect of the intrathecal muscimol and baclofen in distinct phases of neuropathic pain induced by spinal nerve ligation in rats
Brain Research Bulletin, 2016Co-Authors: Q M Dias, Wiliam A PradoAbstract:The abnormal firing of damaged primary afferents and the changes in the central nervous system (CNS) play important role in the initiation and maintenance phases of neuropathic pain. These phases of neuropathic pain involve changes in the GABAergic control of descending pathways that travel through the dorsolateral funiculus (DLF). The present study shows that unilateral DLF lesion increased the antiallodynic effect of muscimol (0.2μg/5μL) (a GABAA receptor agonist) in the initiation, but not maintenance phase of the mechanical allodynia induced by a spinal nerve ligation (SNL) of the ipsilateral hindpaw of rats. The unilateral DLF lesion increased the antiallodynic effect of baclofen (0.8μg/5μL) (a GABAB receptor agonist) in the initiation phase and reduced your effect in the maintenance phase of the mechanical allodynia induced by a spinal nerve ligation (SNL) of the ipsilateral paw of rats. The unilateral DLF lesion significantly reduced the proallodynic effect of an intrathecal injection of Phaclofen (30μg/5μL) (a GABAB receptor antagonist), but not bicuculline (0.3μg/5μL) (a GABAA receptor antagonist). The effect of DLF lesion on the proallodynic effect of Phaclofen was observed in the maintenance, but not in the initiation phase of the mechanical allodynia induced by SNL. We than conclude that the spinal GABAergic neurotransmission is negatively modulated by DLF using GABAA and GABAB receptors, in the initiation phase of mechanical allodynia induced by SNL. In addition, the integrity of DLF is necessary for the effectiveness of GABAergic transmission that occurs via spinal GABAB, but not GABAA receptors, in the maintenance phase of mechanical allodynia induced by SNL.
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the antinociceptive effect of stimulating the retrosplenial cortex in the rat tail flick test but not in the formalin test involves the rostral anterior cingulate cortex
Pharmacology Biochemistry and Behavior, 2015Co-Authors: G M Reis, Rafael Sobrano Fais, Wiliam A PradoAbstract:Abstract The stimulation of the retrosplenial cortex (RSC) is antinociceptive in the rat tail-flick and formalin tests. The rat RSC is caudal to and send projections to the ipsilateral anterior cingulate cortex (ACC), which is also involved in pain processing. This study demonstrated that pre-treating the rostral (rACC), but not the caudal ACC with CoCl 2 (1 mM), or the rACC ablation increased the duration of the antinociceptive effect evoked by a 15-s period of electrical stimulation (AC, 60 Hz, 20 μA) of the RSC in the rat tail-flick. Injecting the GABA-A antagonist bicuculline (50 ng/0.25 μL), but not the GABA-B antagonist Phaclofen (300 ng/0.25 μL) into the rACC also increased the duration of the stimulation-induced antinociception from the RSC. In contrast, the effects of rACC stimulation persisted after the injection of CoCl 2 (1 mM) into the RSC. The injection of CoCl 2 into the rACC did not change the nociceptive behavior of rats during phase 1 of the formalin response but reduced licking response duration during phase 2. This effect was similar in sham or stimulated animals at the RSC. We conclude that the antinociceptive effect of stimulating the RSC in the rat tail-flick test is modulated by the rACC involving GABA-A receptors in this cortex. In contrast, the antinociceptive effect of stimulating the RSC in the formalin test does not involve the rACC.
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spinal mediation of descending pain inhibitory mechanisms activated by 2 100 hz electroacupuncture in the rat tail flick test
Acupuncture and Related Therapies, 2013Co-Authors: Josie R T Silva, Marcelo Lourenco Da Silva, Wiliam A PradoAbstract:Abstract Electroacupuncture (EA) has been widely used for the management of chronic pain, but the mechanism of EA-induced analgesia is not yet fully understood. The present study evaluated the effectiveness of intrathecal antagonists of serotonergic (methysergide), α1- (WB4101) and α2- (idazoxan) adrenoceptors, opioid (naloxone), muscarinic (atropine), GABAA (bicuculline) and GABAB (Phaclofen) receptors in blocking 2/100-Hz electroacupuncture-induced analgesia (EAIA) in the rat tail-flick test. Rats were taken for determination of baseline tail-flick latency (TFL). Vehicle or drug was then injected intrathecally in a volum of 10 μl and EA was applied bilaterally to the Zusanli and Sanyinjiao acupoints under light isoflurane anesthesia. TFL was measured within 30 s after the end of stimulation and at 10-min intervals for up to 60 min. Twenty minutes of 2/100 Hz EA significantly increased TFL. The EAIA was completely inhibited by intrathecal methysergide (30 μg), significantly reduced in intensity and duration by intrathecal idazoxan (50 μg), naloxone (20 μg) or Phaclofen (20 μg), and reduced in duration by intrathecal WB4101 (10 μg), atropine (20 μg) or bicuculline (3 μg). The intensity of the 2/100 Hz-EAIA depends on serotonergic and α2-noradrenergic descending mechanisms, and involves spinal opioid and GABAB modulation. The duration of 2/100 Hz-EAIA depends on both α1- and α2-noradrenergic descending mechanisms, and involves spinal opioid, muscarinic cholinergic, and GABAA and GABAB modulation.
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analgesia induced by 2 or 100 hz electroacupuncture in the rat tail flick test depends on the activation of different descending pain inhibitory mechanisms
The Journal of Pain, 2011Co-Authors: Josie R T Silva, Marcelo Lourenco Da Silva, Wiliam A PradoAbstract:Abstract We evaluated the effectiveness of intrathecal antagonists of α1- (WB4101) and α2- (idazoxan) adrenoceptors and serotonergic (methysergide), opioid (naloxone), muscarinic (atropine), GABA A (bicuculline) and GABA B (Phaclofen) receptors in blocking 2- or 100-Hz electroacupuncture (EA)-induced analgesia (EAIA) in the rat tail-flick test. EA was applied bilaterally to the Zusanli and Sanyinjiao acupoints in lightly anesthetized rats. EA increased tail-flick latency, where the effect of 2-Hz EA lasted longer than that produced by 100-Hz EA. The 2-Hz EAIA was inhibited by naloxone or atropine, was less intense and shorter after WB4101 or idazoxan, and was shorter after methysergide, bicuculline, or Phaclofen. The 100-Hz EAIA was less intense and shorter after naloxone and atropine, less intense and longer after Phaclofen, shorter after methysergide or bicuculline, and remained unchanged after WB4101 or idazoxan. We postulate that the intensity of the effect of 2-Hz EA depends on noradrenergic descending mechanisms and involves spinal opioid and muscarinic mechanisms, whereas the duration of the effect depends on both noradrenergic and serotonergic descending mechanisms, and involves spinal GABAergic modulation. In contrast, the intensity of 100-Hz EAIA involves spinal muscarinic, opioid, and GABA B mechanisms, while the duration of the effects depends on spinal serotonergic, muscarinic, opioid, and GABA A mechanisms. Perspective The results of this study indicate that 2- and 100-Hz EA induce analgesia in the rat tail-flick test activating different descending mechanisms at the spinal cord level that control the intensity and duration of the effect. The adequate pharmacological manipulation of such mechanisms may improve EA effectiveness for pain management.
David I B Kerr - One of the best experts on this subject based on the ideXlab platform.
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differential effects of phosphonic analogues of gaba on gabab autoreceptors in rat neocortical slices
Naunyn-schmiedebergs Archives of Pharmacology, 1998Co-Authors: Jennifer Ong, Victor Marino, D A S Parker, David I B KerrAbstract:The effects of five phosphonic derivatives of GABA on the release of [3H]-GABA from rat neocortical slices, preloaded with [3H]-GABA, were investigated. Phaclofen and 4-aminobutylphosphonic acid (4-ABPA) increased the overflow of [3H] evoked by electrical stimulation (2Hz) in a concentration-dependent manner, with similar potencies (Phaclofen EC50=0.3mmol/l, 4-ABPA EC50=0.4mmol/l). At 3mmol/l, Phaclofen increased the release of [3H]-GABA by 82.6±8.6%, and 4-ABPA increased the release by 81.3±9.0%. 2-Amino-ethylphosphonic acid (2-AEPA) increased the overflow of [3H] by 46.8±10.9% at the highest concentration tested (3mmol/l). In contrast, the lower phosphonic homologue 3-aminopropylphosphonic acid (3-APPA), and 2-amino-2-(p-chlorophenyl)-ethylphosphonic acid (2-CPEPA), a baclofen analogue, did not modify the stimulated overflow. These results suggest that Phaclofen, 4-ABPA and 2-AEPA are antagonists at GABAB autoreceptors, the latter being the weakest antagonist, whilst neither 3-APPA nor 2-CPEPA are active at these receptors. Since Phaclofen, 4-ABPA and 2-CPEPA are antagonists and 3-APPA a partial agonist/antagonist on GABAB heteroreceptors, the lack of effect of 3-APPA and 2-CPEPA on [3H]-GABA release in this study suggests that GABAB autoreceptors may be pharmacologically distinct from the heteroreceptors.
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3-amino-2-(4-chlorophenyl)-nitropropane is a new GABAB receptor agonist, more active peripherally.
European Journal of Pharmacology, 1993Co-Authors: David I B Kerr, Jennifer Ong, John Abbenante, David J. Doolette, Rh PragerAbstract:Abstract The activity of the nitropropane analog of baclofen, 3-amino-2-(4-chlorophenyl)-nitropropane (N-BAC), has been examined at central and peripheral GABAB receptors. N-BAC was less potent than baclofen as a GABAB receptor agonist in depressing repetitive twitch contractions in the guinea-pig isolated ileum (IC50s for baclofen = 4.1 ± 1.3 μM; N-BAC = 9.2 ± 0.3 μM) and vas deferens (IC50s for baclofen = 30 μM; N-BAC = 100 μM), competitively antagonished by Phaclofen, 2-hydroxysaclofen and CGP 35348 (3-aminopropyl-P-di-ethoxymethylphosphinic acid). In the ileum, the pA2 values for CGP 35348 with baclofen (4.7 ± 0.2) and N-BAC (4.6 ± 0.3) were not significantly different (P > 0.05), indicating that both agonists activate the same receptor type. By contrast, in rat neocortical slices, N-BAC was 20 times weaker than baclofen in attenuating spontaneous discharges, sensitive to CGP 35348, whilst it was 100 times less potent than baclofen in depressing evoked CA1 population spikes in the hippocampus. This new GABAB receptor agonist, N-BAC, is thus more active at peripheral than central GABAB receptors.
Xie Peng-yan - One of the best experts on this subject based on the ideXlab platform.
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Effects and mechanisms of electroacupuncture at PC6 on frequency of transient lower esophageal sphincter relaxation in cats
world journal of gastroenterology, 2007Co-Authors: Wang Chi, Zhou De-feng, Shuai Xiao-wei, Liu Jian-xiang, Xie Peng-yanAbstract:AIM: To investigate the effects of electroacupuncture (EA) at neiguan (PC6) on gastric distention-induced transient lower esophageal sphincter relaxations (TLESRs) and discuss the mechanisms of this treatment. METHODS: Protocol I : Twelve healthy cats underwent gastric distention for 60 min on the first day. Electrical acupoint stimulation was applied at the neiguan or a sham point on the hip in randomized order before gastric distention, on the third day and fifth day. Those cats that underwent EA at neiguan on the fifth day were named "Neiguan Group" and the cats that underwent EA at a sham acupoint on the fifth day were named "Sham Group" (control group). During the experiment the frequency of TLESRs and lower esophageal sphincter (LES) pressure were observed by a perfused sleeve assembly. Plasma levels of gastrin (GAS) and motilin (MTL) were determined by radioimmunoassay. Nitrite/nitrate concentration in plasma and tissues were measured by Griess reagent. The nuclei in the brain stem were observed by immunohistochemistry method of c-Fos and NADPH-d dyeing. Protocol II: Thirty six healthy cats were divided into 6 groups randomly. We gave saline (2 mL iv. control group), Phaclofen (5 mg/kg iv. GABA-B antagonist), cholecystokinin octapeptide (CCK-8) (1 mu g/kg per hour iv.), L-Arginine (200 mg/kg iv.), naloxone (2.5 mu mol/kg iv.) and tacrine (5.6 mg/kg ip. cholinesterase inhibitor) respectively before EA at Neiguan and gastric distention. And the frequencies of TLESRs in experimental groups were compared with the control group. RESULTS: Protocol I : Not only the frequency of gastric distention-incluced TLESR in 60 min but also the rate of common cavity during TLESRs were significantly decreased by EA at neiguan compared to that of sham acupoint stimulation. C-Fos immunoreactivity and NOS reactivity in the solitarius (NTS) and dorsal motor nucleus of the vagus (DMV) were significantly decreased by EA at neiguan compared to that of the sham group. However, the positive nuclei of C-Fos and NOS in reticular formation of the medulla (RFM) were increased by EA at neiguan. Protocol H: The inhibited effect of EA at neiguan on TLESRs frequency was completely restored by pretreatment with CCK (23.5/h vs 4.5/h, P < 0.05), L-arginine (17.5/h vs 4.5/h, P < 0.05) and naloxone(12/h vs 4.5/h, P < 0.05). On the contrary, Phaclofen (6/h vs 4.5/h, P > 0.05) and tacrine (9.5/h vs 4.5/h, P > 0.05) did not influence it. CONCLUSION: Electric acupoint stimulation at Neiguan significantly inhibits the frequency of TLESR and the rate of common cavity during TLESR in cats. This effect appears to act on the brain stem, and may be mediated through nitric oxide (NO), CCK-A receptor and mu-opioid receptors. But the GABAB receptor and acetylcholine may not be involved in it. (c) 2007 WJG. All rights reserved.Gastroenterology & HepatologySCI(E)中国科技核心期刊(ISTIC)0364873-48801
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Effects and mechanisms of electroacupuncture at PC6 on frequency of transient lower esophageal sphincter relaxation in cats
world journal of gastroenterology wjg, 2007Co-Authors: Wang Chi, Zhou De-feng, Shuai Xiao-wei, Liu Jian-xiang, Xie Peng-yanAbstract:To investigate the effects of electroacupuncture (EA) at neiguan (PC6) on gastric distention-induced transient lower esophageal sphincter relaxations (TLESRs) and discuss the mechanisms of this treatment.Protocol I: Twelve healthy cats underwent gastric distention for 60 min on the first day. Electrical acupoint stimulation was applied at the neiguan or a sham point on the hip in randomized order before gastric distention, on the third day and fifth day. Those cats that underwent EA at neiguan on the fifth day were named "Neiguan Group" and the cats that underwent EA at a sham acupoint on the fifth day were named "Sham Group" (control group). During the experiment the frequency of TLESRs and lower esophageal sphincter (LES) pressure were observed by a perfused sleeve assembly. Plasma levels of gastrin (GAS) and motilin (MTL) were determined by radioimmunoassay. Nitrite/nitrate concentration in plasma and tissues were measured by Griess reagent. The nuclei in the brain stem were observed by immunohistochemistry method of c-Fos and NADPH-d dyeing. Protocol II: Thirty six healthy cats were divided into 6 groups randomly. We gave saline (2 mL iv. control group), Phaclofen (5 mg/kg iv. GABA-B antagonist), cholecystokinin octapeptide (CCK-8) (1 microg/kg per hour iv.), L-Arginine (200 mg/kg iv.), naloxone (2.5 micromol/kg iv.) and tacrine (5.6 mg/kg ip. cholinesterase inhibitor) respectively before EA at Neiguan and gastric distention. And the frequencies of TLESRs in experimental groups were compared with the control group.Protocol I: Not only the frequency of gastric distention-induced TLESR in 60 min but also the rate of common cavity during TLESRs were significantly decreased by EA at neiguan compared to that of sham acupoint stimulation. C-Fos immunoreactivity and NOS reactivity in the solitarius (NTS) and dorsal motor nucleus of the vagus (DMV) were significantly decreased by EA at neiguan compared to that of the sham group. However, the positive nuclei of C-Fos and NOS in reticular formation of the medulla (RFM) were increased by EA at neiguan. Protocol II: The inhibited effect of EA at neiguan on TLESR's frequency was completely restored by pretreatment with CCK (23.5/h vs 4.5/h, P < 0.05), L-arginine (17.5/h vs 4.5/h, P < 0.05) and naloxone(12/h vs 4.5/h, P < 0.05). On the contrary, Phaclofen (6/h vs 4.5/h, P > 0.05) and tacrine (9.5/h vs 4.5/h, P > 0.05) did not influence it.Electric acupoint stimulation at Neiguan significantly inhibits the frequency of TLESR and the rate of common cavity during TLESR in cats. This effect appears to act on the brain stem, and may be mediated through nitric oxide (NO), CCK-A receptor and mu-opioid receptors. But the GABAB receptor and acetylcholine may not be involved in it.SCI(E)PubMed中国科技核心期刊(ISTIC)0ARTICLE364873-801
Rh Prager - One of the best experts on this subject based on the ideXlab platform.
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3-amino-2-(4-chlorophenyl)-nitropropane is a new GABAB receptor agonist, more active peripherally.
European Journal of Pharmacology, 1993Co-Authors: David I B Kerr, Jennifer Ong, John Abbenante, David J. Doolette, Rh PragerAbstract:Abstract The activity of the nitropropane analog of baclofen, 3-amino-2-(4-chlorophenyl)-nitropropane (N-BAC), has been examined at central and peripheral GABAB receptors. N-BAC was less potent than baclofen as a GABAB receptor agonist in depressing repetitive twitch contractions in the guinea-pig isolated ileum (IC50s for baclofen = 4.1 ± 1.3 μM; N-BAC = 9.2 ± 0.3 μM) and vas deferens (IC50s for baclofen = 30 μM; N-BAC = 100 μM), competitively antagonished by Phaclofen, 2-hydroxysaclofen and CGP 35348 (3-aminopropyl-P-di-ethoxymethylphosphinic acid). In the ileum, the pA2 values for CGP 35348 with baclofen (4.7 ± 0.2) and N-BAC (4.6 ± 0.3) were not significantly different (P > 0.05), indicating that both agonists activate the same receptor type. By contrast, in rat neocortical slices, N-BAC was 20 times weaker than baclofen in attenuating spontaneous discharges, sensitive to CGP 35348, whilst it was 100 times less potent than baclofen in depressing evoked CA1 population spikes in the hippocampus. This new GABAB receptor agonist, N-BAC, is thus more active at peripheral than central GABAB receptors.
Jennifer Ong - One of the best experts on this subject based on the ideXlab platform.
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differential effects of phosphonic analogues of gaba on gabab autoreceptors in rat neocortical slices
Naunyn-schmiedebergs Archives of Pharmacology, 1998Co-Authors: Jennifer Ong, Victor Marino, D A S Parker, David I B KerrAbstract:The effects of five phosphonic derivatives of GABA on the release of [3H]-GABA from rat neocortical slices, preloaded with [3H]-GABA, were investigated. Phaclofen and 4-aminobutylphosphonic acid (4-ABPA) increased the overflow of [3H] evoked by electrical stimulation (2Hz) in a concentration-dependent manner, with similar potencies (Phaclofen EC50=0.3mmol/l, 4-ABPA EC50=0.4mmol/l). At 3mmol/l, Phaclofen increased the release of [3H]-GABA by 82.6±8.6%, and 4-ABPA increased the release by 81.3±9.0%. 2-Amino-ethylphosphonic acid (2-AEPA) increased the overflow of [3H] by 46.8±10.9% at the highest concentration tested (3mmol/l). In contrast, the lower phosphonic homologue 3-aminopropylphosphonic acid (3-APPA), and 2-amino-2-(p-chlorophenyl)-ethylphosphonic acid (2-CPEPA), a baclofen analogue, did not modify the stimulated overflow. These results suggest that Phaclofen, 4-ABPA and 2-AEPA are antagonists at GABAB autoreceptors, the latter being the weakest antagonist, whilst neither 3-APPA nor 2-CPEPA are active at these receptors. Since Phaclofen, 4-ABPA and 2-CPEPA are antagonists and 3-APPA a partial agonist/antagonist on GABAB heteroreceptors, the lack of effect of 3-APPA and 2-CPEPA on [3H]-GABA release in this study suggests that GABAB autoreceptors may be pharmacologically distinct from the heteroreceptors.
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3-amino-2-(4-chlorophenyl)-nitropropane is a new GABAB receptor agonist, more active peripherally.
European Journal of Pharmacology, 1993Co-Authors: David I B Kerr, Jennifer Ong, John Abbenante, David J. Doolette, Rh PragerAbstract:Abstract The activity of the nitropropane analog of baclofen, 3-amino-2-(4-chlorophenyl)-nitropropane (N-BAC), has been examined at central and peripheral GABAB receptors. N-BAC was less potent than baclofen as a GABAB receptor agonist in depressing repetitive twitch contractions in the guinea-pig isolated ileum (IC50s for baclofen = 4.1 ± 1.3 μM; N-BAC = 9.2 ± 0.3 μM) and vas deferens (IC50s for baclofen = 30 μM; N-BAC = 100 μM), competitively antagonished by Phaclofen, 2-hydroxysaclofen and CGP 35348 (3-aminopropyl-P-di-ethoxymethylphosphinic acid). In the ileum, the pA2 values for CGP 35348 with baclofen (4.7 ± 0.2) and N-BAC (4.6 ± 0.3) were not significantly different (P > 0.05), indicating that both agonists activate the same receptor type. By contrast, in rat neocortical slices, N-BAC was 20 times weaker than baclofen in attenuating spontaneous discharges, sensitive to CGP 35348, whilst it was 100 times less potent than baclofen in depressing evoked CA1 population spikes in the hippocampus. This new GABAB receptor agonist, N-BAC, is thus more active at peripheral than central GABAB receptors.
