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Bulleyaconitine A attenuates hyperexcitability of dorsal root ganglion neurons induced by spared nerve injury: The role of preferably blocking Nav1.7 and Nav1.3 channels.
Mol Pain. 2018 Jan-Dec; 14:1744806918778491.MP

Abstract

Background Oral administration of Bulleyaconitine A, an extracted diterpenoid alkaloid from Aconitum bulleyanum plants, is effective for treating chronic pain in rats and in human patients, but the underlying mechanisms are poorly understood. Results As the hyperexcitability of dorsal root ganglion neurons resulting from the upregulation of voltage-gated sodium (Nav) channels has been proved critical for development of chronic pain, we tested the effects of Bulleyaconitine A on Nav channels in rat spared nerve injury model of neuropathic pain. We found that Bulleyaconitine A at 5 nM increased the threshold of action potentials and reduced the firing rate of dorsal root ganglion neurons in spared nerve injury rats but not in sham rats. Bulleyaconitine A preferably blocked tetrodotoxin-sensitive Nav channels over tetrodotoxin-resistant ones in dorsal root ganglion neurons of spared nerve injury rats. Bulleyaconitine A was more potent for blocking Nav1.3 and Nav1.7 than Nav1.8 in cell lines. The half maximal inhibitory concentration (IC50) values for resting Nav1.3, Nav1.7, and Nav1.8 were 995.6 ± 139.1 nM, 125.7 ± 18.6 nM, and 151.2 ± 15.4 μM, respectively, which were much higher than those for inactivated Nav1.3 (20.3 ± 3.4 pM), Nav1.7 (132.9 ± 25.5 pM), and Nav1.8 (18.0 ± 2.5 μM). The most profound use-dependent blocking effect of Bulleyaconitine A was observed on Nav1.7, less on Nav1.3, and least on Nav1.8 at IC50 concentrations. Bulleyaconitine A facilitated the inactivation of Nav channels in each subtype. Conclusions Preferably blocking tetrodotoxin-sensitive Nav1.7 and Nav1.3 in dorsal root ganglion neurons may contribute to Bulleyaconitine A's antineuropathic pain effect.

Authors+Show Affiliations

1 Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.2 Department of Physiology, Pain Research Center, Zhongshan School of Medicine of Sun Yat-Sen University, Guangzhou, China.2 Department of Physiology, Pain Research Center, Zhongshan School of Medicine of Sun Yat-Sen University, Guangzhou, China. 3 Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangdong, China.1 Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.1 Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.4 Department of Pain Medicine, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.2 Department of Physiology, Pain Research Center, Zhongshan School of Medicine of Sun Yat-Sen University, Guangzhou, China. 3 Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangdong, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29783906

Citation

Xie, Man-Xiu, et al. "Bulleyaconitine a Attenuates Hyperexcitability of Dorsal Root Ganglion Neurons Induced By Spared Nerve Injury: the Role of Preferably Blocking Nav1.7 and Nav1.3 Channels." Molecular Pain, vol. 14, 2018, p. 1744806918778491.
Xie MX, Yang J, Pang RP, et al. Bulleyaconitine A attenuates hyperexcitability of dorsal root ganglion neurons induced by spared nerve injury: The role of preferably blocking Nav1.7 and Nav1.3 channels. Mol Pain. 2018;14:1744806918778491.
Xie, M. X., Yang, J., Pang, R. P., Zeng, W. A., Ouyang, H. D., Liu, Y. Q., & Liu, X. G. (2018). Bulleyaconitine A attenuates hyperexcitability of dorsal root ganglion neurons induced by spared nerve injury: The role of preferably blocking Nav1.7 and Nav1.3 channels. Molecular Pain, 14, 1744806918778491. https://doi.org/10.1177/1744806918778491
Xie MX, et al. Bulleyaconitine a Attenuates Hyperexcitability of Dorsal Root Ganglion Neurons Induced By Spared Nerve Injury: the Role of Preferably Blocking Nav1.7 and Nav1.3 Channels. Mol Pain. 2018 Jan-Dec;14:1744806918778491. PubMed PMID: 29783906.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bulleyaconitine A attenuates hyperexcitability of dorsal root ganglion neurons induced by spared nerve injury: The role of preferably blocking Nav1.7 and Nav1.3 channels. AU - Xie,Man-Xiu, AU - Yang,Jie, AU - Pang,Rui-Ping, AU - Zeng,Wei-An, AU - Ouyang,Han-Dong, AU - Liu,Yan-Qing, AU - Liu,Xian-Guo, PY - 2018/5/23/entrez PY - 2018/5/23/pubmed PY - 2018/10/23/medline KW - Bulleyaconitine A KW - dorsal root ganglion KW - neuropathic pain KW - peripheral nerve injury KW - voltage-gated sodium channel SP - 1744806918778491 EP - 1744806918778491 JF - Molecular pain JO - Mol Pain VL - 14 N2 - Background Oral administration of Bulleyaconitine A, an extracted diterpenoid alkaloid from Aconitum bulleyanum plants, is effective for treating chronic pain in rats and in human patients, but the underlying mechanisms are poorly understood. Results As the hyperexcitability of dorsal root ganglion neurons resulting from the upregulation of voltage-gated sodium (Nav) channels has been proved critical for development of chronic pain, we tested the effects of Bulleyaconitine A on Nav channels in rat spared nerve injury model of neuropathic pain. We found that Bulleyaconitine A at 5 nM increased the threshold of action potentials and reduced the firing rate of dorsal root ganglion neurons in spared nerve injury rats but not in sham rats. Bulleyaconitine A preferably blocked tetrodotoxin-sensitive Nav channels over tetrodotoxin-resistant ones in dorsal root ganglion neurons of spared nerve injury rats. Bulleyaconitine A was more potent for blocking Nav1.3 and Nav1.7 than Nav1.8 in cell lines. The half maximal inhibitory concentration (IC50) values for resting Nav1.3, Nav1.7, and Nav1.8 were 995.6 ± 139.1 nM, 125.7 ± 18.6 nM, and 151.2 ± 15.4 μM, respectively, which were much higher than those for inactivated Nav1.3 (20.3 ± 3.4 pM), Nav1.7 (132.9 ± 25.5 pM), and Nav1.8 (18.0 ± 2.5 μM). The most profound use-dependent blocking effect of Bulleyaconitine A was observed on Nav1.7, less on Nav1.3, and least on Nav1.8 at IC50 concentrations. Bulleyaconitine A facilitated the inactivation of Nav channels in each subtype. Conclusions Preferably blocking tetrodotoxin-sensitive Nav1.7 and Nav1.3 in dorsal root ganglion neurons may contribute to Bulleyaconitine A's antineuropathic pain effect. SN - 1744-8069 UR - https://www.unboundmedicine.com/medline/citation/29783906/Bulleyaconitine_A_attenuates_hyperexcitability_of_dorsal_root_ganglion_neurons_induced_by_spared_nerve_injury:_The_role_of_preferably_blocking_Nav1_7_and_Nav1_3_channels_ L2 - http://journals.sagepub.com/doi/full/10.1177/1744806918778491?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -