Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of...Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion （DRG） neurons in chronic neuropathic pain. 24 Sprague-Dawley rats weighing 200--260 g were anesthetized with the intraperitoneal injection of 300 mg· kg^-1 choral hydrate. The CCI model was made by loose ligation of sciatic nerve trunk by 4--0 chromic gut. The mechanical and thermal pain threshold were measured before operation and 1, 3, 5, 7, 9, 11, 13 days after operation. A PE-10 catheter was implanted in subarachnoid space at lumbar region. On the 7th postoperative day the animals were randomly divided into 4 groups. The drugs were injected intrathecally twice a day for 5 consecutive days in group 2--4. The animals were decapitated 14 days after the surgery. The L4--L6 DRG of the operated side was removed and crushed, and total RNA was extracted with Trizol reagent. The contralateral side was used as control. The change of NaV1.8 sodium channel transcripts was determined by RT-PCR. Pain threshold was significantly lowered after CCI as compared with that in control group and was elevated 3 days after antisense oligonucleotide injection. Sensory neuron specific TTX-R sodium channel NaV1.8 transcript was down-regulated after antisense oligonucleotide injection at the dosage of 45 μg as compared with that in CCI group （P〈0.01）, and it was even greater at the dosage of 90 μg. The intrathecally injected NaV1.8 antisense oligonucleotide can reduce the mechanical allodynia and thermal hyperalgesia partially by downregulating the SNS transcript expression.展开更多
Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the ...Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinociceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency （PWL） to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion （DRG） neurons. Results Intraplantar injection of ligustrazine （0.5 mg in 25 μl） significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion （DRG） neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin （TTX） -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron .in the rat.展开更多
Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability,and their abnormal activity is related to several pathological processes,including cardiac arrhythmias,epilepsy,neurod...Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability,and their abnormal activity is related to several pathological processes,including cardiac arrhythmias,epilepsy,neurodegenerative diseases,spasticity and chronic pain.In particular,chronic visceral pain,the central symptom of functional gastrointestinal disorders such as irritable bowel syndrome,is a serious clinical problem that affects a high percentage of the world population.In spite of intense research efforts and after the dedicated decade of pain control and research,there are not many options to treat chronic pain conditions.However,there is a wealth of evidence emerging to give hope that a more refined approach may be achievable.By using electronic databases,available data on structural and functional properties of VGSCs in chronic pain,particularly functional gastrointestinal hypersensitivity,were reviewed.We summarize the involvement and molecular bases of action of VGSCs in the pathophysiology of several organic and functionalgastrointestinal disorders.We also describe the efficacy of VGSC blockers in the treatment of these neurological diseases,and outline future developments that may extend the therapeutic use of compounds that target VGSCs.Overall,clinical and experimental data indicate that isoform-specific blockers of these channels or targeting of their modulators may provide effective and novel approaches for visceral pain therapy.展开更多
Neuropathic pain was produced by chronic constriction injury of the sciatic nerve in rats. Behaviora tests showed that the thresholds for thermal and mechanical hyperalgesia were significantly reduced in neuropathic p...Neuropathic pain was produced by chronic constriction injury of the sciatic nerve in rats. Behaviora tests showed that the thresholds for thermal and mechanical hyperalgesia were significantly reduced in neuropathic pain rats 3 28 days following model induction. The results of immunohistochemistry, western blot assays and reverse transcription-PCR showed that Nay1.7 protein and mRNA expression was significantly increased in the injured dorsal root ganglia. These findings indicated that Nay1.7 might play an important role in the model of chronic neuropathic pain展开更多
Objective: To explore the pathogenesis of trigeminal neuralgia (TN) and to provide a new target for the drug treatment of TN by studying the expression of tetrodotoxin-resistant hNavl. 8 sodium channel protein in affe...Objective: To explore the pathogenesis of trigeminal neuralgia (TN) and to provide a new target for the drug treatment of TN by studying the expression of tetrodotoxin-resistant hNavl. 8 sodium channel protein in affected nerves of patients with TN. Methods: Twelve affected inferior alveolar nerves were obtained from patients with idiopathic TN, to whom the drug therapy was not effective. As negative control, one normal inferior alveolar nerve was obtained from patients who accepted the combined radical neck dissection with glossectomy and mandibulectomy. One muscle sample was obtained as normal control. One dorsal root ganglion from rat was as positive control. These tissues and prepared hNav1.8 antibody were conducted immunohistochemistry response. Results: hNavl. 8 channel protein was expresses in all the 12 specimens of the affected nerves of patients with TN, but not in the muscle sample and the normal inferior alveolar nerve. Conclusion:The abnormal expression of hNavl. 8 channel protein in the affected nerves of patients with TN may play an impo^nt role in the pathogenesis of TN.展开更多
A propagation measurement campaign was performed at the 10 th floor corridor of Xingjian Building,Shanghai University,China.The channel was sounded by pseudo noise( PN) sequence at carrier frequencies of 400-and 2600-...A propagation measurement campaign was performed at the 10 th floor corridor of Xingjian Building,Shanghai University,China.The channel was sounded by pseudo noise( PN) sequence at carrier frequencies of 400-and 2600-MHz respectively.In order to obtain large scale and small scale propagation characteristics in the corridor,the receiver was moved along the corridor every 1.02 meter to record the impulse response.More than 280,000 impulse responses were recorded in the campaign.This work first describes the principle of the measurement,and then how the recorded raw data are processed.The results show that path loss exponent is related to frequency.The relationship between the root-mean squared( RMS) delay spread and the T-R separation distance is analyzed.The RMS delay spread and the mean excess delay spread against path loss are also given,which explain why the 2600 MHz RMS delay spread is larger than that of 400 MHz.展开更多
植物根孔增加大孔隙网络的密度和连通性,促进土壤优先流发生。然而根孔在土壤中分布的构型特征复杂,揭示根孔构型特征影响土壤优先流过程的内在机制,对水资源高效管理、降低地下水污染和滑坡、泥石流等灾害风险具有重要意义。因此,笔者...植物根孔增加大孔隙网络的密度和连通性,促进土壤优先流发生。然而根孔在土壤中分布的构型特征复杂,揭示根孔构型特征影响土壤优先流过程的内在机制,对水资源高效管理、降低地下水污染和滑坡、泥石流等灾害风险具有重要意义。因此,笔者通过Web of Science和中国知网等数据库,检索获取截至2020年的相关研究文献,主要综述根孔构型的影响因素、量化方法及其对土壤优先流影响的研究进展,发现植物种类、年限季节、土壤属性等均会改变根孔的构型特征,但各因素的作用机制仍不清楚;CT扫描成像技术是量化根孔构型特征的有效方法;通过大孔隙阻断方法,能实地量化土壤入渗过程中优先流过程和基质入渗过程;植物根孔有效改良土壤入渗性能,土壤优先流通量与根孔数量、直径、表面积和体积等二维参数呈正相关关系。今后应深入研究根孔发育机制及其构型特征。加强根孔构型对土壤优先流过程的影响及作用机制的研究,是深入揭示土壤优先流运动机理的重要方向。展开更多
基金the National Natural Science Foundation of China(No.30470559,30330230,30240059)the National Basic Research Development Program(973)of China(No.2007CB512501)Beijing Natural Science Foundation(No.7052039)
文摘Dorsal root ganglion(DRG)neurons have peripheral terminals in skin,muscle,and other peripheral tissues,andcentral
文摘Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion （DRG） neurons in chronic neuropathic pain. 24 Sprague-Dawley rats weighing 200--260 g were anesthetized with the intraperitoneal injection of 300 mg· kg^-1 choral hydrate. The CCI model was made by loose ligation of sciatic nerve trunk by 4--0 chromic gut. The mechanical and thermal pain threshold were measured before operation and 1, 3, 5, 7, 9, 11, 13 days after operation. A PE-10 catheter was implanted in subarachnoid space at lumbar region. On the 7th postoperative day the animals were randomly divided into 4 groups. The drugs were injected intrathecally twice a day for 5 consecutive days in group 2--4. The animals were decapitated 14 days after the surgery. The L4--L6 DRG of the operated side was removed and crushed, and total RNA was extracted with Trizol reagent. The contralateral side was used as control. The change of NaV1.8 sodium channel transcripts was determined by RT-PCR. Pain threshold was significantly lowered after CCI as compared with that in control group and was elevated 3 days after antisense oligonucleotide injection. Sensory neuron specific TTX-R sodium channel NaV1.8 transcript was down-regulated after antisense oligonucleotide injection at the dosage of 45 μg as compared with that in CCI group （P〈0.01）, and it was even greater at the dosage of 90 μg. The intrathecally injected NaV1.8 antisense oligonucleotide can reduce the mechanical allodynia and thermal hyperalgesia partially by downregulating the SNS transcript expression.
文摘Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinociceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency （PWL） to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion （DRG） neurons. Results Intraplantar injection of ligustrazine （0.5 mg in 25 μl） significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion （DRG） neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin （TTX） -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron .in the rat.
文摘Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability,and their abnormal activity is related to several pathological processes,including cardiac arrhythmias,epilepsy,neurodegenerative diseases,spasticity and chronic pain.In particular,chronic visceral pain,the central symptom of functional gastrointestinal disorders such as irritable bowel syndrome,is a serious clinical problem that affects a high percentage of the world population.In spite of intense research efforts and after the dedicated decade of pain control and research,there are not many options to treat chronic pain conditions.However,there is a wealth of evidence emerging to give hope that a more refined approach may be achievable.By using electronic databases,available data on structural and functional properties of VGSCs in chronic pain,particularly functional gastrointestinal hypersensitivity,were reviewed.We summarize the involvement and molecular bases of action of VGSCs in the pathophysiology of several organic and functionalgastrointestinal disorders.We also describe the efficacy of VGSC blockers in the treatment of these neurological diseases,and outline future developments that may extend the therapeutic use of compounds that target VGSCs.Overall,clinical and experimental data indicate that isoform-specific blockers of these channels or targeting of their modulators may provide effective and novel approaches for visceral pain therapy.
基金This study was supported by the National Natural Science Foundation of China(The mechanism of Na_v 1.7 (encoded by SCN9A gene) activated by chronic neuropathic pain and the experimental study of analgesia by SCN9A RNAi), No.81171059
文摘Neuropathic pain was produced by chronic constriction injury of the sciatic nerve in rats. Behaviora tests showed that the thresholds for thermal and mechanical hyperalgesia were significantly reduced in neuropathic pain rats 3 28 days following model induction. The results of immunohistochemistry, western blot assays and reverse transcription-PCR showed that Nay1.7 protein and mRNA expression was significantly increased in the injured dorsal root ganglia. These findings indicated that Nay1.7 might play an important role in the model of chronic neuropathic pain
文摘Objective: To explore the pathogenesis of trigeminal neuralgia (TN) and to provide a new target for the drug treatment of TN by studying the expression of tetrodotoxin-resistant hNavl. 8 sodium channel protein in affected nerves of patients with TN. Methods: Twelve affected inferior alveolar nerves were obtained from patients with idiopathic TN, to whom the drug therapy was not effective. As negative control, one normal inferior alveolar nerve was obtained from patients who accepted the combined radical neck dissection with glossectomy and mandibulectomy. One muscle sample was obtained as normal control. One dorsal root ganglion from rat was as positive control. These tissues and prepared hNav1.8 antibody were conducted immunohistochemistry response. Results: hNavl. 8 channel protein was expresses in all the 12 specimens of the affected nerves of patients with TN, but not in the muscle sample and the normal inferior alveolar nerve. Conclusion:The abnormal expression of hNavl. 8 channel protein in the affected nerves of patients with TN may play an impo^nt role in the pathogenesis of TN.
基金Supported by the National Natural Science Foundation of China(No.61132003,61171086,61501186)Shanghai Natural Science Foundation under Grant(No.14ZR1415100)
文摘A propagation measurement campaign was performed at the 10 th floor corridor of Xingjian Building,Shanghai University,China.The channel was sounded by pseudo noise( PN) sequence at carrier frequencies of 400-and 2600-MHz respectively.In order to obtain large scale and small scale propagation characteristics in the corridor,the receiver was moved along the corridor every 1.02 meter to record the impulse response.More than 280,000 impulse responses were recorded in the campaign.This work first describes the principle of the measurement,and then how the recorded raw data are processed.The results show that path loss exponent is related to frequency.The relationship between the root-mean squared( RMS) delay spread and the T-R separation distance is analyzed.The RMS delay spread and the mean excess delay spread against path loss are also given,which explain why the 2600 MHz RMS delay spread is larger than that of 400 MHz.
文摘植物根孔增加大孔隙网络的密度和连通性,促进土壤优先流发生。然而根孔在土壤中分布的构型特征复杂,揭示根孔构型特征影响土壤优先流过程的内在机制,对水资源高效管理、降低地下水污染和滑坡、泥石流等灾害风险具有重要意义。因此,笔者通过Web of Science和中国知网等数据库,检索获取截至2020年的相关研究文献,主要综述根孔构型的影响因素、量化方法及其对土壤优先流影响的研究进展,发现植物种类、年限季节、土壤属性等均会改变根孔的构型特征,但各因素的作用机制仍不清楚;CT扫描成像技术是量化根孔构型特征的有效方法;通过大孔隙阻断方法,能实地量化土壤入渗过程中优先流过程和基质入渗过程;植物根孔有效改良土壤入渗性能,土壤优先流通量与根孔数量、直径、表面积和体积等二维参数呈正相关关系。今后应深入研究根孔发育机制及其构型特征。加强根孔构型对土壤优先流过程的影响及作用机制的研究,是深入揭示土壤优先流运动机理的重要方向。
