Sodium Channel Inhibitors (Nav1.7, 1.8, And 1.9) For Neuropathic Pain Management

Yingyi Lai

doi:10.54097/wghqc383

Authors

Yingyi Lai

DOI:

https://doi.org/10.54097/wghqc383

Keywords:

Neuropathic Pain; Sodium Channels; Nav1.7; Nav1.8; Nav1.9; Sodium Channel Blockers; Pain Management.

Abstract

This paper explores the potential of voltage-gated sodium channels, specifically Nav1.7, Nav1.8, and Nav1.9, in the management of neuropathic pain. Neuropathic pain, a complex and chronic condition resistant to conventional treatments, poses a significant clinical challenge. Recent research has shed light on the role of these sodium channel isoforms, predominantly found in peripheral sensory neurons, as novel targets for analgesic development. In this study, we delve into the structural and functional aspects of these channels, their involvement in action potential generation and propagation, and their contribution to neuropathic pain. Furthermore, we review the development and clinical efficacy of selective sodium channel inhibitors, addressing associated challenges and discussing potential future directions in this promising field. Our paper aims to emphasize the potential of sodium channel blockers as a promising approach to neuropathic pain treatment, highlighting their role in providing targeted pain relief with potentially fewer side effects. The contributions of this study include new insights into the role of specific sodium channel isoforms, the evaluation of selective inhibitors, and an overview of the challenges and opportunities in this field of pain managemen.

Downloads

Download data is not yet available.

References

Quintans JS, Antoniolli AR, Almeida JR, Santana‐Filho VJ, Quintans‐Júnior LJ. Natural products evaluated in neuropathic pain models‐a systematic review. Basic & clinical pharmacology & toxicology. 2014 Jun;114(6):442-50.

De Gray LC, Matta BF. Acute and chronic pain following craniotomy: a review. Anaesthesia. 2005 Jul;60(7):693-704.

Zghoul N, Ross EL, Edwards RR, Ahmed A, Jamison RN. Prevalence of chronic pain with neuropathic characteristics: a randomized telephone survey among medical center patients in Kuwait. J Pain Res. 2017 Apr 4; 10:679-687. doi: 10.2147/JPR.S123966. PMID: 28435312; PMCID: PMC5388267.

Wood JN, Boorman JP, Okuse K, Baker MD. Voltage‐gated sodium channels and pain pathways. Journal of neurobiology. 2004 Oct;61(1):55-71.

Bennett DL, Clark AJ, Huang J, Waxman SG, Dib-Hajj SD. The role of voltage-gated sodium channels in pain signaling. Physiological reviews. 2019 Apr 1;99(2):1079-151.

Rogers M, Tang L, Madge DJ, Stevens EB. The role of sodium channels in neuropathic pain. InSeminars in cell & developmental biology 2006 Oct 1 (Vol. 17, No. 5, pp. 571-581). Academic Press.

Kühn H, Kappes L, Wolf K, Gebhardt L, Neurath MF, Reeh P, Fischer MJ, Kremer AE. Complementary roles of murine NaV1. 7, NaV1. 8 and NaV1. 9 in acute itch signalling. Scientific Reports. 2020 Feb 11;10(1):2326.

Okura D, Horishita T, Ueno S, Yanagihara N, Sudo Y, Uezono Y, Sata T. The endocannabinoid anandamide inhibits voltage-gated sodium channels Nav1. 2, Nav1. 6, Nav1. 7, and Nav1. 8 in Xenopus oocytes. Anesthesia & Analgesia. 2014 Mar 1;118(3):554-62.

Imbrici P, Liantonio A, Camerino GM, De Bellis M, Camerino C, Mele A, Giustino A, Pierno S, De Luca A, Tricarico D, Desaphy JF, Conte D. Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery. Front Pharmacol. 2016 May 10; 7:121. doi: 10.3389/fphar.2016.00121. PMID: 27242528; PMCID: PMC4861771.

Nieto FR, Cobos EJ, Tejada MÁ, Sánchez-Fernández C, González-Cano R, Cendán CM. Tetrodotoxin (TTX) as a therapeutic agent for pain. Marine drugs. 2012 Jan 31;10(2):281-305.

Chang W, Berta T, Kim YH, Lee S, Lee SY, Ji RR. Expression and role of voltage-gated sodium channels in human dorsal root ganglion neurons with special focus on Nav1. 7, species differences, and regulation by paclitaxel. Neuroscience bulletin. 2018 Feb; 34:4-12.

Dib-Hajj, S., Yang, Y., Black, J. et al. The NaV1.7 sodium channel: from molecule to man. Nat Rev Neurosci 14, 49–62 (2013).

Swanwick, Richard & Pristerà, Alessandro & Okuse, Kenji. (2010). The trafficking of Na(V)1.8. Neuroscience letters. 486. 78-83. 10.1016/j.neulet.2010.08.074.

Dib-Hajj, S., Black, J. & Waxman, S. NaV1.9: a sodium channel linked to human pain. Nat Rev Neurosci 16, 511–519 (2015).

Qi FH, Zhou YL, Xu GY. Targeting voltage-gated sodium channels for treatment for chronic visceral pain. World J Gastroenterol 2011; 17(19): 2357-2364 [PMID: 21633634 DOI: 10.3748/wjg. v17.i19.2357]

Hameed S. Nav1.7 and Nav1.8: Role in the pathophysiology of pain. Molecular Pain. 2019;15. doi:10.1177/1744806919858801

Perrot S, Cittée J, Louis P, Quentin B, Robert C, Milon JY, Bismut H, Baumelou A. Self‐medication in pain management: The state of the art of pharmacists’ role for optimal Over‐The‐Counter analgesic use. European Journal of Pain. 2019 Nov;23(10):1747-62.

Lampert A, O’Reilly AO, Reeh P, Leffler A. Sodium channelopathies and pain. Pflügers Archiv-European Journal of Physiology. 2010 Jul; 460:249-63.

Alsaloum M, Higerd GP, Effraim PR, Waxman SG. Status of peripheral sodium channel blockers for non-addictive pain treatment. Nature Reviews Neurology. 2020 Dec;16(12):689-705.

Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, Freeman R, Truini A, Attal N, Finnerup NB, Eccleston C. Neuropathic pain. Nature reviews Disease primers. 2017 Feb 16;3(1):1-9.

Cheng Qiyun, Sun Caixin, Zhang Xiaoxing, et al. Short-Term load forecasting model and method for power system based on complementation of neural network and fuzzy logic. Transactions of China Electrotechnical Society, 2004, 19(10): 53-58.