Mechanisms Underlying Gastrodin Alleviating Vincristine-Induced Peripheral Neuropathic Pain

Overview

Journal Front Pharmacol

Date 2022 Jan 3

PMID 34975470

Citations 7

Authors

Xiangyu Wang

Boxuan Zhang

Xuedong Li

Xingang Liu

Songsong Wang

Yuan Xie

Jialing Pi

Zhiyuan Yang

Jincan Li

Qingzhong Jia

Yang Zhang

Affiliations

Soon will be listed here.

Abstract

Gastrodin (GAS) is the main bioactive ingredient of Gastrodia, a famous Chinese herbal medicine widely used as an analgesic, but the underlying analgesic mechanism is still unclear. In this study, we first observed the effects of GAS on the vincristine-induced peripheral neuropathic pain by alleviating the mechanical and thermal hyperalgesia. Further studies showed that GAS could inhibit the current density of Na1.7 and Na1.8 channels and accelerate the inactivation process of Na1.7 and Na1.8 channel, thereby inhibiting the hyperexcitability of neurons. Additionally, GAS could significantly reduce the over-expression of Na1.7 and Na1.8 on DRG neurons from vincristine-treated rats according to the analysis of Western blot and immunofluorescence results. Moreover, based on the molecular docking and molecular dynamic simulation, the binding free energies of the constructed systems were calculated, and the binding sites of GAS on the sodium channels (Na1.7 and Na1.8) were preliminarily determined. This study has shown that modulation of Na1.7 and Na1.8 sodium channels by GAS contributing to the alleviation of vincristine-induced peripheral neuropathic pain, thus expanding the understanding of complex action of GAS as a neuromodulator.

Citing Articles

Unlocking New Therapeutic Options for Vincristine-Induced Neuropathic Pain: The Impact of Preclinical Research.

Puscasu C, Negres S, Zbarcea C, Chirita C Life (Basel). 2024; 14(11).

PMID: 39598298 PMC: 11595627. DOI: 10.3390/life14111500.

A comprehensive review of traditional Chinese medicine in treating neuropathic pain.

Hu N, Liu J, Luo Y, Li Y Heliyon. 2024; 10(17):e37350.

PMID: 39296122 PMC: 11407996. DOI: 10.1016/j.heliyon.2024.e37350.

Gastrodin Ameliorates Post-Stroke Depressive-Like Behaviors Through Cannabinoid-1 Receptor-Dependent PKA/RhoA Signaling Pathway.

Wang S, Yu L, Guo H, Zuo W, Guo Y, Liu H Mol Neurobiol. 2024; 62(1):366-385.

PMID: 38856794 DOI: 10.1007/s12035-024-04267-5.

Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy.

Chen X, Gan Y, Au N, Ma C Front Mol Neurosci. 2024; 17:1345811.

PMID: 38660386 PMC: 11039947. DOI: 10.3389/fnmol.2024.1345811.

Review on pharmacological effects of gastrodin.

Xiao G, Tang R, Yang N, Chen Y Arch Pharm Res. 2023; 46(9-10):744-770.

PMID: 37749449 DOI: 10.1007/s12272-023-01463-0.

References

Nepal M, Jeong K, Kim G, Cha D, Kang M, Kim J . Role of Intestinal Microbiota in Metabolism of Gastrodin In Vitro and In Vivo. Metabolites. 2019; 9(4). PMC: 6523420. DOI: 10.3390/metabo9040069. View

Chen S, Hao X, Yu L, Zhang P, Cao W, Chen H . Gastrodin causes vasodilation by activating K channels in vascular smooth muscles via PKA-dependent signaling pathway. J Recept Signal Transduct Res. 2017; 37(6):543-549. DOI: 10.1080/10799893.2017.1369118. View

Argyriou A, Cavaletti G, Antonacopoulou A, Genazzani A, Briani C, Bruna J . Voltage-gated sodium channel polymorphisms play a pivotal role in the development of oxaliplatin-induced peripheral neurotoxicity: results from a prospective multicenter study. Cancer. 2013; 119(19):3570-7. DOI: 10.1002/cncr.28234. View

Aromolaran K, Goldstein P . Ion channels and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy; cause and effect?. Mol Pain. 2017; 13:1744806917714693. PMC: 5480635. DOI: 10.1177/1744806917714693. View

Norcini M, Sideris A, Adler S, Hernandez L, Zhang J, Blanck T . NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity. Front Mol Neurosci. 2016; 9:100. PMC: 5068091. DOI: 10.3389/fnmol.2016.00100. View

Sun T, Wang J, Li X, Li Y, Feng D, Shi W . Gastrodin relieved complete Freund's adjuvant-induced spontaneous pain by inhibiting inflammatory response. Int Immunopharmacol. 2016; 41:66-73. DOI: 10.1016/j.intimp.2016.10.020. View

Zhang H, Dougherty P . Enhanced excitability of primary sensory neurons and altered gene expression of neuronal ion channels in dorsal root ganglion in paclitaxel-induced peripheral neuropathy. Anesthesiology. 2014; 120(6):1463-75. PMC: 4031279. DOI: 10.1097/ALN.0000000000000176. View

Sapunar D, Kostic S, Banozic A, Puljak L . Dorsal root ganglion - a potential new therapeutic target for neuropathic pain. J Pain Res. 2012; 5:31-8. PMC: 3287412. DOI: 10.2147/JPR.S26603. View

Wang J, Zheng Y, Chen Y, Gu M, Gao Z, Nan F . Discovery of aryl sulfonamide-selective Nav1.7 inhibitors with a highly hydrophobic ethanoanthracene core. Acta Pharmacol Sin. 2019; 41(3):293-302. PMC: 7471454. DOI: 10.1038/s41401-019-0267-z. View

10.

Jackson T, Thomas S, Stabile V, Han X, Shotwell M, McQueen K . Prevalence of chronic pain in low-income and middle-income countries: a systematic review and meta-analysis. Lancet. 2015; 385 Suppl 2:S10. DOI: 10.1016/S0140-6736(15)60805-4. View

11.

Herzog R, Cummins T, Ghassemi F, Dib-Hajj S, Waxman S . Distinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neurons. J Physiol. 2003; 551(Pt 3):741-50. PMC: 2343279. DOI: 10.1113/jphysiol.2003.047357. View

12.

Xia Z, Xiao Y, Wu Y, Zhao B . Sodium channel Nav1.7 expression is upregulated in the dorsal root ganglia in a rat model of paclitaxel-induced peripheral neuropathy. Springerplus. 2016; 5(1):1738. PMC: 5053969. DOI: 10.1186/s40064-016-3351-6. View

13.

Kingwell K . Nav1.7 withholds its pain potential. Nat Rev Drug Discov. 2019; . DOI: 10.1038/d41573-019-00065-0. View

14.

Xu T, Li D, Zhou X, Ouyang H, Zhou L, Zhou H . Oral Application of Magnesium-L-Threonate Attenuates Vincristine-induced Allodynia and Hyperalgesia by Normalization of Tumor Necrosis Factor-α/Nuclear Factor-κB Signaling. Anesthesiology. 2017; 126(6):1151-1168. DOI: 10.1097/ALN.0000000000001601. View

15.

Shields S, Cheng X, Uceyler N, Sommer C, Dib-Hajj S, Waxman S . Sodium channel Na(v)1.7 is essential for lowering heat pain threshold after burn injury. J Neurosci. 2012; 32(32):10819-32. PMC: 6621015. DOI: 10.1523/JNEUROSCI.0304-12.2012. View

16.

Chen L, Huang J, Benson C, Lankford K, Zhao P, Carrara J . Sodium channel Nav1.6 in sensory neurons contributes to vincristine-induced allodynia. Brain. 2020; 143(8):2421-2436. DOI: 10.1093/brain/awaa208. View

17.

Tanner K, Reichling D, Levine J . Nociceptor hyper-responsiveness during vincristine-induced painful peripheral neuropathy in the rat. J Neurosci. 1998; 18(16):6480-91. PMC: 6793188. View

18.

Zhang F, Wang Y, Liu Y, Han H, Zhang D, Fan X . Transcriptional Regulation of Voltage-Gated Sodium Channels Contributes to GM-CSF-Induced Pain. J Neurosci. 2019; 39(26):5222-5233. PMC: 6595947. DOI: 10.1523/JNEUROSCI.2204-18.2019. View

19.

Black J, Liu S, Tanaka M, Cummins T, Waxman S . Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Pain. 2004; 108(3):237-247. DOI: 10.1016/j.pain.2003.12.035. View

20.

Xu H, Li T, Rohou A, Arthur C, Tzakoniati F, Wong E . Structural Basis of Nav1.7 Inhibition by a Gating-Modifier Spider Toxin. Cell. 2019; 176(5):1238-1239. DOI: 10.1016/j.cell.2019.01.047. View