Objective:To evaluate the effect of down-regulation of Nav1.7 on the activation of astrocytes and microglia in DRG of rats with cancer pain,and explore the transmission of the nociceptive information.Methods:Lentivira...Objective:To evaluate the effect of down-regulation of Nav1.7 on the activation of astrocytes and microglia in DRG of rats with cancer pain,and explore the transmission of the nociceptive information.Methods:Lentiviral vector harboring RNAi sequence targeting the Navl.7 gene was constructed,and Walker 256 breast cancer cell and morphine was injected to build the bone cancer pain model and morphine tolerance model in rats.Lentiviral vector was injected.Rats in each model were divided into 4 groups:model group,PBS group,vehicle group and LV-Nav1.7 group.The expression levels of GFAP and OX42 in dorsal root ganglia(DRG) were measured.Results:After the animal model was built,the level of Navl.7,GFAP and OX42 was improved obviously with the time prolonged,which was statistically significant(P<0.05).The expression level of GFAP and OX42 in the DRG in the LV-Navl.7 group declined obviously compared to the model group,PBS group and vehicle group(P<0.05).Conclusions:Intrathecal injection of Navl.7 shRNA lentiviral vector can reduce the expression of Nav1.7and inhibit the activation of astrocytes and microglia in DRG.The effort is also effective in morphine tolerance bone cancer pain model rats.展开更多
Objective The aim of this study was to examine the effects of photodynamic therapy(PDT)on the expression of Nav1.7 in spinal dorsal root ganglion(DRG)neurons.Methods The primary DRG neurons from newborn SD rats were c...Objective The aim of this study was to examine the effects of photodynamic therapy(PDT)on the expression of Nav1.7 in spinal dorsal root ganglion(DRG)neurons.Methods The primary DRG neurons from newborn SD rats were cultured.The cells were identified by neuron-specific enolase immunofluorescence staining.DRG neurons were divided into four groups:control group,photosensitizer group,laser group,and PDT group.The cell viability was detected by a cell counting kit-8(CCK8)assay.qRT-PCR and Western blotting were used to determine the mRNA and protein expression levels of Nav1.7 in DRG neurons.Results The purity of the cultured primary DRG neurons was greater than 90%.Compared with the control group,no significant change was found in the cell viability of the photosensitizer group,while the viability in the laser group and the PDT group was significantly reduced.The mRNA and protein expression levels of Nav1.7 were significantly greater in the laser group and the PDT group than in the control group.At the same time,the mRNA and protein expression levels of Nav1.7 were greater in the laser group than in the PDT group.Conclusion Both laser and PDT could upregulate the expression of Nav1.7 in DRG neurons,and the promoting effect might be related to the pain induced by clinical treatment.This study provides a research basis for the use of laser and PDT to treat pain.A better understanding of the relationship between Nav1.7 and PDT can help clinicians better manage PDT-related pain.展开更多
Various peptide toxins in animal venom inhibit voltage-gated sodium ion channel Nav1.7, including Nav-targeting spider toxin(NaSpTx) Family I. Toxins in NaSpTx Family I share a similar structure, i.e., Nterminal, loop...Various peptide toxins in animal venom inhibit voltage-gated sodium ion channel Nav1.7, including Nav-targeting spider toxin(NaSpTx) Family I. Toxins in NaSpTx Family I share a similar structure, i.e., Nterminal, loops 1–4, and C-terminal. Here, we used Mu-theraphotoxin-Ca2a(Ca2a), a peptide isolated from Cyriopagopus albostriatus, as a template to investigate the general properties of toxins in NaSpTx Family I. The toxins interacted with the cell membrane prior to binding to Nav1.7 via similar hydrophobic residues. Residues in loop 1, loop 4,and the C-terminal primarily interacted with the S3–S4 linker of domain II, especially basic amino acids binding to E818. We also identified the critical role of loop 2 in Ca2a regarding its affinity to Nav1.7.Our results provide further evidence that NaSpTx Family I toxins share similar structures and mechanisms of binding to Nav1.7.展开更多
Anti-cancer chemotherapy is.usually associated withperipheral neurotoxicity,which may result in severe pain hypersensitivity.Our previous study verified that miR-30b mediated the up-regulation of voltage gated sodium ...Anti-cancer chemotherapy is.usually associated withperipheral neurotoxicity,which may result in severe pain hypersensitivity.Our previous study verified that miR-30b mediated the up-regulation of voltage gated sodium channel 1.6(Nav1.6)in the dorsal root ganglia(DRG)of rats with oxaliplatin(OXA)-induced neuropathic pain(OIPN).However,the mechanism of how miR-30b is changed remains elusive.In the current study,we found that the level of TET1 as well as the hydroxymethylation level in miR-30b promotor were significantly decreased in the L3-L5 DRG of OIPN mice.展开更多
基金supported by National Natural Science Foundation of China(NO.81201395)
文摘Objective:To evaluate the effect of down-regulation of Nav1.7 on the activation of astrocytes and microglia in DRG of rats with cancer pain,and explore the transmission of the nociceptive information.Methods:Lentiviral vector harboring RNAi sequence targeting the Navl.7 gene was constructed,and Walker 256 breast cancer cell and morphine was injected to build the bone cancer pain model and morphine tolerance model in rats.Lentiviral vector was injected.Rats in each model were divided into 4 groups:model group,PBS group,vehicle group and LV-Nav1.7 group.The expression levels of GFAP and OX42 in dorsal root ganglia(DRG) were measured.Results:After the animal model was built,the level of Navl.7,GFAP and OX42 was improved obviously with the time prolonged,which was statistically significant(P<0.05).The expression level of GFAP and OX42 in the DRG in the LV-Navl.7 group declined obviously compared to the model group,PBS group and vehicle group(P<0.05).Conclusions:Intrathecal injection of Navl.7 shRNA lentiviral vector can reduce the expression of Nav1.7and inhibit the activation of astrocytes and microglia in DRG.The effort is also effective in morphine tolerance bone cancer pain model rats.
基金supported by Natural Science Foundation of Beijing Municipality(No.7202200)Central Military Commission Health Care Project(No.20BJZ13)Air Force Equipment Scientific Research Project(No.KJ20201A050226).
文摘Objective The aim of this study was to examine the effects of photodynamic therapy(PDT)on the expression of Nav1.7 in spinal dorsal root ganglion(DRG)neurons.Methods The primary DRG neurons from newborn SD rats were cultured.The cells were identified by neuron-specific enolase immunofluorescence staining.DRG neurons were divided into four groups:control group,photosensitizer group,laser group,and PDT group.The cell viability was detected by a cell counting kit-8(CCK8)assay.qRT-PCR and Western blotting were used to determine the mRNA and protein expression levels of Nav1.7 in DRG neurons.Results The purity of the cultured primary DRG neurons was greater than 90%.Compared with the control group,no significant change was found in the cell viability of the photosensitizer group,while the viability in the laser group and the PDT group was significantly reduced.The mRNA and protein expression levels of Nav1.7 were significantly greater in the laser group and the PDT group than in the control group.At the same time,the mRNA and protein expression levels of Nav1.7 were greater in the laser group than in the PDT group.Conclusion Both laser and PDT could upregulate the expression of Nav1.7 in DRG neurons,and the promoting effect might be related to the pain induced by clinical treatment.This study provides a research basis for the use of laser and PDT to treat pain.A better understanding of the relationship between Nav1.7 and PDT can help clinicians better manage PDT-related pain.
基金supported by the National Natural Science Foundation of China (31971190)Science Fund for Distinguished Young Scholars of Hunan Province (2021JJ10035)Education Department of Hunan Province (19A321)。
文摘Various peptide toxins in animal venom inhibit voltage-gated sodium ion channel Nav1.7, including Nav-targeting spider toxin(NaSpTx) Family I. Toxins in NaSpTx Family I share a similar structure, i.e., Nterminal, loops 1–4, and C-terminal. Here, we used Mu-theraphotoxin-Ca2a(Ca2a), a peptide isolated from Cyriopagopus albostriatus, as a template to investigate the general properties of toxins in NaSpTx Family I. The toxins interacted with the cell membrane prior to binding to Nav1.7 via similar hydrophobic residues. Residues in loop 1, loop 4,and the C-terminal primarily interacted with the S3–S4 linker of domain II, especially basic amino acids binding to E818. We also identified the critical role of loop 2 in Ca2a regarding its affinity to Nav1.7.Our results provide further evidence that NaSpTx Family I toxins share similar structures and mechanisms of binding to Nav1.7.
文摘Anti-cancer chemotherapy is.usually associated withperipheral neurotoxicity,which may result in severe pain hypersensitivity.Our previous study verified that miR-30b mediated the up-regulation of voltage gated sodium channel 1.6(Nav1.6)in the dorsal root ganglia(DRG)of rats with oxaliplatin(OXA)-induced neuropathic pain(OIPN).However,the mechanism of how miR-30b is changed remains elusive.In the current study,we found that the level of TET1 as well as the hydroxymethylation level in miR-30b promotor were significantly decreased in the L3-L5 DRG of OIPN mice.
