Bulleyaconitine A preferably reduces tetrodotoxin-sensitive sodium current in uninjured dorsal root ganglion neurons of neuropathic rats probably via inhibition of protein kinase C
| Autor: | Jie Yang, Shao-Kun Wang, Xian-Guo Liu, Kai-Feng Shen, Xiao-Long Zhang, Xiongxiong Zhong, Yan-Qing Liu, Man-Xiu Xie, Rui-Ping Pang, Jing Xu |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine SNi medicine.medical_specialty Patch-Clamp Techniques Time Factors Sensory Receptor Cells Aconitine Tetrodotoxin Voltage-Gated Sodium Channels Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Cadmium Chloride Dorsal root ganglion Ganglia Spinal Internal medicine medicine Animals Patch clamp Enzyme Inhibitors Protein Kinase C Protein kinase C Chemistry Sodium channel Nerve injury Electric Stimulation Rats Disease Models Animal 030104 developmental biology Anesthesiology and Pain Medicine medicine.anatomical_structure Endocrinology Gene Expression Regulation nervous system Neurology Hyperalgesia Peripheral nerve injury Neuropathic pain Neuralgia Neurology (clinical) medicine.symptom 030217 neurology & neurosurgery Sodium Channel Blockers |
| Zdroj: | Pain. 158:2169-2180 |
| ISSN: | 1872-6623 0304-3959 |
| DOI: | 10.1097/j.pain.0000000000001018 |
| Popis: | Oral Bulleyaconitine A (BLA) is effective for treating neuropathic pain in human patients, but the underlying mechanism is poorly understood. Here, we tested whether BLA blocked voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons. Compelling evidence shows that voltage-gated sodium channels are upregulated in uninjured DRG neurons but downregulated in injured ones following peripheral nerve injury. We found that BLA preferably inhibited Na currents in uninjured DRG neurons in neuropathic rats. Compared to sham rats, IC50 values for resting and inactivated Na currents were 113 and 74 times lower in injured and uninjured neurons of L4-6 DRGs in spared nerve injury (SNI) rats (4.55 and 0.56 nM) and were 688 and 518 times lower in the uninjured L4 and L6 DRG neurons of L5 spinal nerve ligation (L5-SNL) rats. The use-dependent blockage of BLA on Na currents was more potent in neuropathic rats compared to sham rats. Bulleyaconitine A facilitated the inactivation of Na channels in each group. IC50 values for resting and inactivated tetrodotoxin-sensitive (TTX-S) channels were 1855 and 1843 times lower than those for TTX-resistant channels in the uninjured neurons of L5 spinal nerve ligation rats. The upregulation of protein kinase C was associated with the preferable effect of BLA on TTX-S Na channels in the uninjured DRG neurons. Local application of BLA onto L4-6 DRGs at 0.1 to 10 nM dose-dependently alleviated the mechanical allodynia and thermal hyperalgesia in L5 spinal nerve ligation model. Thus, preferable blockage of TTX-S Na channels in uninjured DRG neurons may contribute to BLA's antineuropathic pain effect. |
| Databáze: | OpenAIRE |
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