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Zhaoxiang Bian - One of the best experts on this subject based on the ideXlab platform.
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Analgesic Effect of paeoniflorin in rats with neonatal maternal separation induced visceral hyperalgesia is mediated through adenosine a1 receptor by inhibiting the extracellular signal regulated protein kinase erk pathway
Pharmacology Biochemistry and Behavior, 2009Co-Authors: Xiaojun Zhang, Hongli Chen, Hongqi Zhang, Joseph J Y Sung, Zhaoxiang BianAbstract:Abstract Paeoniflorin (PF), a chief active ingredient in the root of Paeonia lactiflora Pall (family Ranunculaceae), is Effective in relieving colorectal distention (CRD)-induced visceral pain in rats with visceral hyperalgesia induced by neonatal maternal separation (NMS). This study aimed at exploring the underlying mechanisms of PF's Analgesic Effect on CRD-evoked nociceptive signaling in the central nervous system (CNS) and investigating whether the adenosine A 1 receptor is involved in PF's anti-nociception. Results : CRD-induced visceral pain as well as phosphorylated-extracellular signal-regulated protein kinase (p-ERK) and phospho-cAMP response element-binding protein (p-CREB) expression in the CNS structures of NMS rats were suppressed by NMDA receptor antagonist dizocilpine (MK-801) and ERK phosphorylation inhibitor U0126. PF could similarly inhibit CRD-evoked p-ERK and c-Fos expression in laminae I–II of the lumbosacral dorsal horn and anterior cingulate cortex (ACC). PF could also reverse the CRD-evoked increased glutamate concentration by CRD as shown by dynamic microdialysis monitoring in ACC, whereas, DPCPX, an antagonist of adenosine A 1 receptor, significantly blocked the Analgesic Effect of PF and PF's inhibition on CRD-induced p-ERK and p-CREB expression. These results suggest that PF's Analgesic Effect is possibly mediated by adenosine A 1 receptor by inhibiting CRD-evoked glutamate release and the NMDA receptor dependent ERK signaling.
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the Analgesic Effect of paeoniflorin on neonatal maternal separation induced visceral hyperalgesia in rats
The Journal of Pain, 2008Co-Authors: Xiaojun Zhang, Zhi Li, Waimui Leung, Hongxi Xu, Zhaoxiang BianAbstract:Abstract Paeoniflorin (PF) is one of the principle active ingredients of the root of Paeonia lactiflora Pall (family Ranunculaceae), a Chinese herb traditionally used to relieve pain, especially visceral pain. The present study aimed to investigate both the Effect of PF on neonatal maternal separation–induced visceral hyperalgesia in rats and the mechanism by which such Effect is exerted. A dose-dependent Analgesic Effect was produced by PF (45, 90, 180, and 360 mg/kg i.p.). Centrally administered PF (4.5 mg/kg i.c.v) also produced a significant Analgesic Effect. The Analgesic Effect of PF (45 mg/kg i.p.) was maximal at 30 minutes after administration. Furthermore, it was found that nor-binaltorphimine (nor-BNI, 3 mg/kg i.p.), dl-α-methyltyrosine (α-AMPT, 250 mg/kg i.p.), and yohimbine (3 mg/kg i.p.) could block the Analgesic Effect of PF (45 mg/kg i.p.). Time course determination of PF in brain nuclei showed that the maximal concentration of PF was 30 minutes after intraperitoneal administration of PF (180 mg/kg) in cerebral nuclei, involving the amygdala, hypothalamus, thalamus, and cortex. These data indicate that PF has an Analgesic Effect on visceral pain in rats with neonatal maternal separation and that this Effect may be mediated by κ-opioid receptors and α 2 -adrenoceptors in the central nervous system. Perspective This study demonstrates that PF has an Analgesic Effect on pain in visceral hyperalgesic rats. These results suggest that PF might be potentially useful in clinical therapy for irritable bowel syndrome as a pharmacological agent in alleviating visceral pain.
Dacheng Wang - One of the best experts on this subject based on the ideXlab platform.
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structure of an excitatory insect specific toxin with an Analgesic Effect on mammals from the scorpion buthus martensii karsch
Acta Crystallographica Section D-biological Crystallography, 2004Co-Authors: R J Guan, Ye Xiang, Ying Zhang, Dacheng WangAbstract:BmK IT-AP is an excitatory insect-specific beta-toxin with Analgesic Effect from the Chinese scorpion Buthus martensii Karsch (BmK) and consists of 72 residues cross-linked by four disulfide bridges. The crystal structure of BmK IT-AP has been determined at a resolution of 2.6 A by molecular replacement. Compared with the mammal-selective alpha-toxins consisting of 64 residues from the scorpion BmK, the general fold of IT-AP features an additional one-and-a-half turn alpha-helix at the C-terminal residues 59-65 with a shifted disulfide bridge Cys38-Cys64. The extension and 'wiggling' of the C-terminal segment led to a reshaping of the bioactive surface, including the complete destruction of the active site RC comprising the reverse turn (8-12) and C-terminal residues 58-64, the disappearance of an active surface formed by two aromatic residues Trp38 and Tyr42 and the covering of the conserved aromatic cluster Tyr5, Tyr35 and Trp47, which are all critical for the structure and function of mammal-selective alpha-toxins. Bj-xtrIT, the only other excitatory insect-specific toxin whose three-dimensional structure has been determined, is distinct from BmK IT-AP. A functionally important five-residue alpha-helix (alpha0) formed by residues 17-21 in Bj-xtrIT is deleted in BmK IT-AP and helix alpha1 is immediately connected to Cys16 through two residues Leu17 and Phe18. Accordingly, the functional surface of this region in Bj-xtrIT has also been reshaped in IT-AP, which implies subtle differences between BmK IT-AP and Bj-xtrIT in binding to the receptor, although most other critical residues for structure and function adopt almost identical conformations. The crystal structure of IT-AP also forms a sound basis for further study of the structure-function determinants of the Analgesic Effect.
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A depressant insect toxin with a novel Analgesic Effect from scorpion Buthus martensii Karsch
Biochimica et biophysica acta, 2001Co-Authors: R J Guan, Chunguang Wang, M Wang, Dacheng WangAbstract:A new peptide named BmK dITAP3 from scorpion Buthus martensii Karsch (BmK) has been identified to possess a dual bioactivity, a depressant neurotoxicity on insects and an Analgesic Effect on mice. The bioassays also showed that the peptide was definitely devoid of the neurotoxicity on mammals, which indicated that the Analgesic Effect of BmK dITAP3 could not be ascribed to the syndromic Effects of a mammalian neurotoxicity. BmK dITAP3 exhibited 43.0% inhibition efficiency of the Analgesic Effect on mice at a dose of 5 mg/kg and the FPU value of 0.5 microg/body (approximately 30 mg) on the fly larvae. The pI value and the molecular mass determined by MALDI-TOF MS for dITAP3 were 6.5 and 6722.7, respectively. Its first 15 N-terminal residues were determined by Edman degradation, based on which the full amino acid sequence was deduced from the cDNA sequence encoding the peptide with 3'-RACE. Circular dichroism and sequence based prediction analyses showed dITAP3 may have a similar molecular scaffold as the most scorpion toxins but with features of the more beta structures and much less of alpha helix. The details of the purification, characterization and sequencing as well as the sequence comparison with other depressant insect toxins and the correlation between the Analgesic Effect and the insect toxicity will be reported and discussed, respectively.
R J Guan - One of the best experts on this subject based on the ideXlab platform.
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structure of an excitatory insect specific toxin with an Analgesic Effect on mammals from the scorpion buthus martensii karsch
Acta Crystallographica Section D-biological Crystallography, 2004Co-Authors: R J Guan, Ye Xiang, Ying Zhang, Dacheng WangAbstract:BmK IT-AP is an excitatory insect-specific beta-toxin with Analgesic Effect from the Chinese scorpion Buthus martensii Karsch (BmK) and consists of 72 residues cross-linked by four disulfide bridges. The crystal structure of BmK IT-AP has been determined at a resolution of 2.6 A by molecular replacement. Compared with the mammal-selective alpha-toxins consisting of 64 residues from the scorpion BmK, the general fold of IT-AP features an additional one-and-a-half turn alpha-helix at the C-terminal residues 59-65 with a shifted disulfide bridge Cys38-Cys64. The extension and 'wiggling' of the C-terminal segment led to a reshaping of the bioactive surface, including the complete destruction of the active site RC comprising the reverse turn (8-12) and C-terminal residues 58-64, the disappearance of an active surface formed by two aromatic residues Trp38 and Tyr42 and the covering of the conserved aromatic cluster Tyr5, Tyr35 and Trp47, which are all critical for the structure and function of mammal-selective alpha-toxins. Bj-xtrIT, the only other excitatory insect-specific toxin whose three-dimensional structure has been determined, is distinct from BmK IT-AP. A functionally important five-residue alpha-helix (alpha0) formed by residues 17-21 in Bj-xtrIT is deleted in BmK IT-AP and helix alpha1 is immediately connected to Cys16 through two residues Leu17 and Phe18. Accordingly, the functional surface of this region in Bj-xtrIT has also been reshaped in IT-AP, which implies subtle differences between BmK IT-AP and Bj-xtrIT in binding to the receptor, although most other critical residues for structure and function adopt almost identical conformations. The crystal structure of IT-AP also forms a sound basis for further study of the structure-function determinants of the Analgesic Effect.
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A depressant insect toxin with a novel Analgesic Effect from scorpion Buthus martensii Karsch
Biochimica et biophysica acta, 2001Co-Authors: R J Guan, Chunguang Wang, M Wang, Dacheng WangAbstract:A new peptide named BmK dITAP3 from scorpion Buthus martensii Karsch (BmK) has been identified to possess a dual bioactivity, a depressant neurotoxicity on insects and an Analgesic Effect on mice. The bioassays also showed that the peptide was definitely devoid of the neurotoxicity on mammals, which indicated that the Analgesic Effect of BmK dITAP3 could not be ascribed to the syndromic Effects of a mammalian neurotoxicity. BmK dITAP3 exhibited 43.0% inhibition efficiency of the Analgesic Effect on mice at a dose of 5 mg/kg and the FPU value of 0.5 microg/body (approximately 30 mg) on the fly larvae. The pI value and the molecular mass determined by MALDI-TOF MS for dITAP3 were 6.5 and 6722.7, respectively. Its first 15 N-terminal residues were determined by Edman degradation, based on which the full amino acid sequence was deduced from the cDNA sequence encoding the peptide with 3'-RACE. Circular dichroism and sequence based prediction analyses showed dITAP3 may have a similar molecular scaffold as the most scorpion toxins but with features of the more beta structures and much less of alpha helix. The details of the purification, characterization and sequencing as well as the sequence comparison with other depressant insect toxins and the correlation between the Analgesic Effect and the insect toxicity will be reported and discussed, respectively.
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A new insect neurotoxin AngP1 with Analgesic Effect from the scorpion Buthus martensii Karsch: purification and characterization.
The journal of peptide research : official journal of the American Peptide Society, 2001Co-Authors: R J Guan, M Wang, D C Wang, Deyu WangAbstract:An insect toxin named BmK AngP1 was purified from the venom of the scorpion Buthus martensii Karsch (BmK). It also shows an evident Analgesic Effect on mice, but is interestingly devoid of mammalian toxicity. Bioassay showed that the CPU value of AngP1 was 0.01 microg/body ( approximately 30 mg) for the excitatory insect toxicity and 43.0% inhibition efficiency for analgesia at a dose of 5 mg/kg. However, even at the dosage of 10 mg/kg no detectable toxicity on mice could be found. The isoelectric point (pI) value for AngP1 was 4.0, and its molecular mass analyzed by MALDI-TOF MS was 8141.0. The first 15 N-terminal residues of AngP1 were determined by Edman degradation and showed high similarity to that of other excitatory scorpion insect toxins. The circular dichroism spectroscopy measured on a JASCO J-720 system showed that there were 10.4% alpha-helix, 46.2% beta-strand and 14.1% turn structure in this peptide. Under two conditions single crystals of AngP1 were obtained.
Soren Hein Sindrup - One of the best experts on this subject based on the ideXlab platform.
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the Analgesic Effect of tramadol after intravenous injection in healthy volunteers in relation to cyp2d6
Anesthesia & Analgesia, 2006Co-Authors: Thomas P Enggaard, Joachim Ossig, Kim Brosen, L K Poulsen, Lars Arendtnielsen, Soren Hein SindrupAbstract:Tramadol analgesia results from a monoaminergic Effect by tramadol itself and an opioid Effect of its metabolite (+)-M1 formed by O-demethylation of tramadol by CYP2D6. In this study we sought to determine the impact of (+)-M1 on the Analgesic Effect of tramadol evaluated by experimental pain models. The Effect of an IV injection of 100 mg tramadol on experimental pain was studied 15-90 min after dosing in volunteers, 10 extensive metabolizers with CYP2D6 and 10 poor metabolizers without CYP2D6 in 2 placebo-controlled trials. The pain tests included detection and tolerance threshold to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation (temporal summation), and the cold pressor test. In extensive metabolizers, tramadol reduced discomfort experienced during the cold pressor test (P = 0.002). In poor metabolizers, the pain tolerance thresholds to sural nerve stimulation were increased (P = 0.04). (+)-M1 could be detected in the serum samples from all extensive metabolizers except one, but (+)-M1 was below the limit of determination in all poor metabolizers. The opioid Effect of (+)-M1 appears to contribute to the Analgesic Effect of tramadol, but the monoaminergic Effect of tramadol itself seems to create an Analgesic Effect.
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the Analgesic Effect of tramadol after intravenous injection in healthy volunteers in relation to cyp2d6
Anesthesia & Analgesia, 2006Co-Authors: Thomas P Enggaard, Joachim Ossig, Kim Brosen, L K Poulsen, Lars Arendtnielsen, Soren Hein SindrupAbstract:Tramadol analgesia results from a monoaminergic Effect by tramadol itself and an opioid Effect of its metabolite ()-M1 formed by O-demethylation of tramadol by CYP2D6. In this study we sought to determine the impact of ()-M1 on the Analgesic Effect of tramadol
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codeine and morphine in extensive and poor metabolizers of sparteine pharmacokinetics Analgesic Effect and side Effects
European Journal of Clinical Pharmacology, 1996Co-Authors: Lars Poulsen, Karsten Elbaek, Lars F. Gram, Kim Brosen, Lars Arendtnielsen, Soren Hein SindrupAbstract:Objective: Codeine O-demethylation to morphine is catalysed by the genetic polymorphic sparteine oxygenase (CYP2D6). The objective of the present study was to assess the Analgesic Effect of codeine on different types of experimental pain in relation to sparteine phenotype. Methods: Fourteen extensive (EMs) and 14 poor metabolizers (PMs) of sparteine completed a randomized, double-blind, three-way, cross-over study with a single oral dose of codeine (75 or 100 mg) against morphine (20 or 30 mg) and placebo. Pain tests performed before and 1, 2, 3, and 4 h after medication included the cold pressor test and pain thresholds for heat and pressure stimulation. Adverse Effects were rated by a structured interview. Results: After morphine, morphine and morphine-6-glucuronide were present in equal amounts in plasma of PMs and EMs. After codeine, neither morphine nor morphine-6-glucuronide could be detected in 13 of the 14 PMs, whereas at least one of the compounds could be detected in all EMs. Peak pain and discomfort rated on a VAS scale during the cold pressor test were significantly reduced by morphine in both EMs and PMs, with a median peak change of 8.5 and 7.0 mm, respectively, for peak pain, and 11.5 and 15.5 mm, respectively, for discomfort. Codeine only reduced these pain measures significantly in EMs, with a median peak change of 5.5 mm for peak pain and 10.5 mm for discomfort. Pain detection and tolerance thresholds to heat and pressure were not consistently altered by either morphine or codeine. In PMs, adverse Effects were significantly more pronounced on morphine than on codeine and only showed a slight difference between codeine and placebo. In EMs, there was no difference between codeine and morphine and more pronounced adverse Effects on both drugs as compared to placebo. Conclusions: This study confirms that codeine O-demethylation depends on CYP2D6; it shows that the 6-glucuronidation of morphine is independent of CYP2D6; it supports the theory that the Analgesic Effect of codeine depends on its O-demethylation; and it indicates that this is probably also the case for the adverse Effects. The resuls lend no support to the suggestion of a non-opioid Analgesic Effect of codeine.
E. Hille - One of the best experts on this subject based on the ideXlab platform.
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THE Analgesic Effect OF ACUPUNCTURE IN CHRONIC TENNIS ELBOW PAIN
British journal of rheumatology, 1994Co-Authors: A. Molsberger, E. HilleAbstract:The immediate Analgesic Effect of a single non-segmental acupuncture stimulation treatment on chronic tennis elbow pain was studied in a placebo-controlled single-blind trial completed by 48 patients. Before and after treatment, all patients were examined physically by an unbiased independent examiner. Eleven-point box scales were used [13] for pain measurement. Patients in the verum group were treated at non-segmental distal points (homolateral leg) for elbow pain following Chinese acupuncture rules, whereas patients in the placebo group were treated with placebo acupuncture avoiding penetration of the skin with an acupuncture needle. Overall reduction in the pain score was 55.8% (S = 2.95) in the verum group and 15% (S = 2.77) in the placebo group. After one treatment 19 out of 24 patients in the verum group (79.2%) reported pain relief of at least 50% (placebo group: six patients out of 24). The average duration of analgesia after one treatment was 20.2 h in the verum group (S = 21.54) and 1.4 h (S = 3.50) in the placebo group. The results are statistically significant (P < 0.01); they show that non-segmental verum acupuncture has an intrinsic Analgesic Effect in the clinical treatment of tennis elbow pain which exceeds that of placebo acupuncture.