Puerarin Relieves Paclitaxel-Induced Neuropathic Pain: The Role of Na1.8 β1 Subunit of Sensory Neurons

Overview

Journal Front Pharmacol

Date 2019 Jan 23

PMID 30666203

Citations 19

Authors

Xiao-Long Zhang

Xian-Ying Cao

Ren-Chun Lai

Man-Xiu Xie

Wei-An Zeng

Affiliations

Soon will be listed here.

Abstract

Currently there is no effective treatment available for clinical patients suffering from neuropathic pain induced by chemotherapy paclitaxel. Puerarin is a major isoflavonoid extracted from the Chinese medical herb kudzu root, which has been used for treatment of cardiovascular disorders and brain injury. Here, we found that puerarin dose-dependently alleviated paclitaxel-induced neuropathic pain. At the same time, puerarin preferentially reduced the excitability and blocked the voltage-gated sodium (Na) channels of dorsal root ganglion (DRG) neurons from paclitaxel-induced neuropathic pain rats. Furthermore, puerarin was a more potent blocker of tetrodotoxin-resistant (TTX-R) Na channels than of tetrodotoxin-sensitive (TTX-S) Na channels in chronic pain rats' DRG neurons. In addition, puerarin had a stronger blocking effect on Na1.8 channels in DRG neurons of neuropathic pain rats and β1 subunit siRNA can abolish this selective blocking effect on Na1.8. Together, these results suggested that puerarin may preferentially block β1 subunit of Na1.8 in sensory neurons contributed to its anti-paclitaxel induced neuropathic pain effect.

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References

Blackburn-Munro G, Fleetwood-Walker S . The sodium channel auxiliary subunits beta1 and beta2 are differentially expressed in the spinal cord of neuropathic rats. Neuroscience. 1999; 90(1):153-64. DOI: 10.1016/s0306-4522(98)00415-1. View

Porreca F, Lai J, Bian D, Wegert S, Ossipov M, Eglen R . A comparison of the potential role of the tetrodotoxin-insensitive sodium channels, PN3/SNS and NaN/SNS2, in rat models of chronic pain. Proc Natl Acad Sci U S A. 1999; 96(14):7640-4. PMC: 33594. DOI: 10.1073/pnas.96.14.7640. View

Liu X, Eschenfelder S, Blenk K, Janig W, Habler H . Spontaneous activity of axotomized afferent neurons after L5 spinal nerve injury in rats. Pain. 2000; 84(2-3):309-18. DOI: 10.1016/s0304-3959(99)00211-0. View

Lyu Y, Park S, Chung K, Chung J . Low dose of tetrodotoxin reduces neuropathic pain behaviors in an animal model. Brain Res. 2000; 871(1):98-103. DOI: 10.1016/s0006-8993(00)02451-3. View

Cavaletti G, Cavalletti E, Oggioni N, Sottani C, Minoia C, DIncalci M . Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration. Neurotoxicology. 2000; 21(3):389-93. View

Ong B, Tomaselli G, Balser J . A structural rearrangement in the sodium channel pore linked to slow inactivation and use dependence. J Gen Physiol. 2000; 116(5):653-62. PMC: 2229478. DOI: 10.1085/jgp.116.5.653. View

Kerr B, Souslova V, McMahon S, Wood J . A role for the TTX-resistant sodium channel Nav 1.8 in NGF-induced hyperalgesia, but not neuropathic pain. Neuroreport. 2001; 12(14):3077-80. DOI: 10.1097/00001756-200110080-00019. View

Lai J, Gold M, Kim C, Bian D, Ossipov M, Hunter J . Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8. Pain. 2002; 95(1-2):143-52. DOI: 10.1016/s0304-3959(01)00391-8. View

Fang X, Djouhri L, Black J, Dib-Hajj S, Waxman S, Lawson S . The presence and role of the tetrodotoxin-resistant sodium channel Na(v)1.9 (NaN) in nociceptive primary afferent neurons. J Neurosci. 2002; 22(17):7425-33. PMC: 6757987. View

10.

Laird J, Souslova V, Wood J, Cervero F . Deficits in visceral pain and referred hyperalgesia in Nav1.8 (SNS/PN3)-null mice. J Neurosci. 2002; 22(19):8352-6. PMC: 6757795. View

11.

Djouhri L, Newton R, Levinson S, Berry C, Carruthers B, Lawson S . Sensory and electrophysiological properties of guinea-pig sensory neurones expressing Nav 1.7 (PN1) Na+ channel alpha subunit protein. J Physiol. 2003; 546(Pt 2):565-76. PMC: 2342520. DOI: 10.1113/jphysiol.2002.026559. View

12.

Roy M, Narahashi T . Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons. J Neurosci. 1992; 12(6):2104-11. PMC: 6575921. View

13.

Isom L, De Jongh K, Patton D, Reber B, Offord J, Charbonneau H . Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. Science. 1992; 256(5058):839-42. DOI: 10.1126/science.1375395. View

14.

Blair N, Bean B . Role of tetrodotoxin-resistant Na+ current slow inactivation in adaptation of action potential firing in small-diameter dorsal root ganglion neurons. J Neurosci. 2003; 23(32):10338-50. PMC: 6741008. View

15.

Lai J, Porreca F, Hunter J, Gold M . Voltage-gated sodium channels and hyperalgesia. Annu Rev Pharmacol Toxicol. 2004; 44:371-97. DOI: 10.1146/annurev.pharmtox.44.101802.121627. View

16.

Dougherty P, Cata J, Cordella J, Burton A, Weng H . Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain. 2004; 109(1-2):132-42. DOI: 10.1016/j.pain.2004.01.021. View

17.

Chevrier P, Vijayaragavan K, Chahine M . Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by the local anesthetic lidocaine. Br J Pharmacol. 2004; 142(3):576-84. PMC: 1574965. DOI: 10.1038/sj.bjp.0705796. View

18.

Chahine M, Ziane R, Vijayaragavan K, Okamura Y . Regulation of Na v channels in sensory neurons. Trends Pharmacol Sci. 2005; 26(10):496-502. DOI: 10.1016/j.tips.2005.08.002. View

19.

Catterall W, Goldin A, Waxman S . International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev. 2005; 57(4):397-409. DOI: 10.1124/pr.57.4.4. View

20.

Armstrong D, Bundy B, Wenzel L, Huang H, Baergen R, Lele S . Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006; 354(1):34-43. DOI: 10.1056/NEJMoa052985. View