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
Voltage-gated sodium channels （Navs） play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained h...Voltage-gated sodium channels （Navs） play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion （hDRG） tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Navl.7 （,-~ 50% of total Nav expression） and lower expres- sion of Navl.8 （~ 12%）, whereas the mouse DRG has higher expression of Nav 1.8 （- 45%） and lower expression of Navl.7 （- 18%）. To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary cultures with paclitaxel （0.1-1 μmol/L） for 24 h. Paclitaxel increased the Navl.7 but not Navl.8 expression and also increased the transient Na＋ currents and action potential firing frequency in small-diameter （〈50 ~tm） hDRG neurons. Thus, the hDRG provides a translational model in which to study ＂human pain in a dish＂ and test new pain therapeutics.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
High-voltage-activated(HVA) Ca^(2+)channels are widely expressed in the nervous system. They play an important role in pain conduction by participating in various physiological processes such as synaptic transmission,...High-voltage-activated(HVA) Ca^(2+)channels are widely expressed in the nervous system. They play an important role in pain conduction by participating in various physiological processes such as synaptic transmission, changes in synaptic plasticity, and neuronal excitability. Available evidence suggests that the HVA channel is an important therapeutic target for pain management. In this review, we summarize the changes in different subtypes of HVA channel during pain and present the currently available evidence from the clinical application of HVA channel blockers. We also review novel drugs in various phases of development. Moreover, we discuss the future prospects of HVA channel blockers in order to promote ‘‘bench-to-bedside'' translation.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 investigate whether the effect of loureirin B plus capsaicin on tetrodotoxin-resistant(TTX-R) sodium channel.METHODS: By using whole-cell patch-clamp recordings, in acutely isolated dorsal root ganglion(...OBJECTIVE: To investigate whether the effect of loureirin B plus capsaicin on tetrodotoxin-resistant(TTX-R) sodium channel.METHODS: By using whole-cell patch-clamp recordings, in acutely isolated dorsal root ganglion(DRG) neurons, the combined effects of loureirin B and capsaicin on TTX-R sodium channel were observed. Based on the data, the interaction between loureirin B and capsaicin in their modulation on TTX-R sodium channel was assessed.RESULTS: Loureirin B could not induce transient inward TRPV1 current. Capsazepine, a transient receptor potential vanilloid l(TRPV1) antagonist, could not attenuate the block of 0.64 mmol/L loureirin B on TTX-R sodium channel. There was no significant difference(P > 0.05) between IC_(50) of loureirin B(0.37 mmol/L) on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that(0.38 mmol/L)in capsaicin-insensitive DRG neurons. However,there was a significant difference(P < 0.05) between the IC_(50) of capsaicin(0.28 μmol/L) on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that(52.24 μmol/L) in capsaicin-insensitive DRG neurons. Four combinations composed of various concentrations of loureirin B and capsaicin could all inhibit TTX-R sodium currents but have different interactions between loureirin B and capsaicin.CONCLUSION: Loureirin B plus capsaicin could produce double blockage on TRPV1 and modulation on TTX-R sodium channel. The action of loureirin B onTTX-R sodium channel was independent ofTRPV1 but similar with that of capsaicin on TTX-R sodium channel in capsaicin-insensitive DRG neurons.展开更多
第五代移动通信技术(5th-generation mobile communication technology,5G)网络对高速率、低时延、高可靠性的移动通信处理需求不断增加,对终端基带信道估计算法的高性能和低复杂度设计、矩阵处理动态范围提出挑战。针对上述问题,本文...第五代移动通信技术(5th-generation mobile communication technology,5G)网络对高速率、低时延、高可靠性的移动通信处理需求不断增加,对终端基带信道估计算法的高性能和低复杂度设计、矩阵处理动态范围提出挑战。针对上述问题,本文提出一种基于相关矩阵托普利兹(Toeplitz)特性的信道估计算法。依据信道的相干带宽特性计算信道相关矩阵并保留必要的较低矩阵阶数;基于相关矩阵的Toeplitz特性设计低复杂度的递归求逆算法,并针对加权矩阵乘法的元素重复性将矩阵乘法化简为矩阵点乘,简化加权矩阵运算;同时引入跟踪信噪比变化的缩放补偿因子对计算过程和结果分别进行缩放和补偿。理论分析和仿真结果显示,本文所提算法可在达到优异的信道估计性能条件下,有效降低运算复杂度,并极大降低算法矩阵处理的动态范围。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
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.
基金supported in part by NIH RO1Grants NS87988,DE17794,and DE22743 to R.R.J and NS89479 to S.Y.L and R.R.J
文摘Voltage-gated sodium channels （Navs） play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion （hDRG） tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Navl.7 （,-~ 50% of total Nav expression） and lower expres- sion of Navl.8 （~ 12%）, whereas the mouse DRG has higher expression of Nav 1.8 （- 45%） and lower expression of Navl.7 （- 18%）. To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary cultures with paclitaxel （0.1-1 μmol/L） for 24 h. Paclitaxel increased the Navl.7 but not Navl.8 expression and also increased the transient Na＋ currents and action potential firing frequency in small-diameter （〈50 ~tm） hDRG neurons. Thus, the hDRG provides a translational model in which to study ＂human pain in a dish＂ and test new pain therapeutics.
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.
基金supported by the National Natural Science Foundation of China (81701092)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Support (20171916)Shanghai Municipal Commission of Health and Family Planning Funding for Key Developing Disciplines (2015ZB0101)
文摘High-voltage-activated(HVA) Ca^(2+)channels are widely expressed in the nervous system. They play an important role in pain conduction by participating in various physiological processes such as synaptic transmission, changes in synaptic plasticity, and neuronal excitability. Available evidence suggests that the HVA channel is an important therapeutic target for pain management. In this review, we summarize the changes in different subtypes of HVA channel during pain and present the currently available evidence from the clinical application of HVA channel blockers. We also review novel drugs in various phases of development. Moreover, we discuss the future prospects of HVA channel blockers in order to promote ‘‘bench-to-bedside'' translation.
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
基金Supported by the National Natural Science Foundation of China(No.81403186)National Science Foundation of Hubei Grants(No.2014CFB455)
文摘OBJECTIVE: To investigate whether the effect of loureirin B plus capsaicin on tetrodotoxin-resistant(TTX-R) sodium channel.METHODS: By using whole-cell patch-clamp recordings, in acutely isolated dorsal root ganglion(DRG) neurons, the combined effects of loureirin B and capsaicin on TTX-R sodium channel were observed. Based on the data, the interaction between loureirin B and capsaicin in their modulation on TTX-R sodium channel was assessed.RESULTS: Loureirin B could not induce transient inward TRPV1 current. Capsazepine, a transient receptor potential vanilloid l(TRPV1) antagonist, could not attenuate the block of 0.64 mmol/L loureirin B on TTX-R sodium channel. There was no significant difference(P > 0.05) between IC_(50) of loureirin B(0.37 mmol/L) on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that(0.38 mmol/L)in capsaicin-insensitive DRG neurons. However,there was a significant difference(P < 0.05) between the IC_(50) of capsaicin(0.28 μmol/L) on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that(52.24 μmol/L) in capsaicin-insensitive DRG neurons. Four combinations composed of various concentrations of loureirin B and capsaicin could all inhibit TTX-R sodium currents but have different interactions between loureirin B and capsaicin.CONCLUSION: Loureirin B plus capsaicin could produce double blockage on TRPV1 and modulation on TTX-R sodium channel. The action of loureirin B onTTX-R sodium channel was independent ofTRPV1 but similar with that of capsaicin on TTX-R sodium channel in capsaicin-insensitive DRG neurons.
文摘第五代移动通信技术(5th-generation mobile communication technology,5G)网络对高速率、低时延、高可靠性的移动通信处理需求不断增加,对终端基带信道估计算法的高性能和低复杂度设计、矩阵处理动态范围提出挑战。针对上述问题,本文提出一种基于相关矩阵托普利兹(Toeplitz)特性的信道估计算法。依据信道的相干带宽特性计算信道相关矩阵并保留必要的较低矩阵阶数;基于相关矩阵的Toeplitz特性设计低复杂度的递归求逆算法,并针对加权矩阵乘法的元素重复性将矩阵乘法化简为矩阵点乘,简化加权矩阵运算;同时引入跟踪信噪比变化的缩放补偿因子对计算过程和结果分别进行缩放和补偿。理论分析和仿真结果显示,本文所提算法可在达到优异的信道估计性能条件下,有效降低运算复杂度,并极大降低算法矩阵处理的动态范围。
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.
