Nanomedicine and voltage-gated sodium channel blockers in pain management: a game changer or a lost cause?

Drug Deliv Transl Res. 2024 Aug;14(8):2112-2145. doi: 10.1007/s13346-024-01615-9. Epub 2024 Jun 11.

Abstract

Pain, a complex and debilitating condition affecting millions globally, is a significant concern, especially in the context of post-operative recovery. This comprehensive review explores the complexity of pain and its global impact, emphasizing the modulation of voltage-gated sodium channels (VGSC or NaV channels) as a promising avenue for pain management with the aim of reducing reliance on opioids. The article delves into the role of specific NaV isoforms, particularly NaV 1.7, NaV 1.8, and NaV 1.9, in pain process and discusses the development of sodium channel blockers to target these isoforms precisely. Traditional local anesthetics and selective NaV isoform inhibitors, despite showing varying efficacy in pain management, face challenges in systemic distribution and potential side effects. The review highlights the potential of nanomedicine in improving the delivery of local anesthetics, toxins and selective NaV isoform inhibitors for a targeted and sustained release at the site of pain. This innovative strategy seeks to improve drug bioavailability, minimize systemic exposure, and optimize therapeutic outcomes, holding significant promise for secure pain management and enhancing the quality of life for individuals recovering from surgical procedures or suffering from chronic pain.

Keywords: NaV channel blockers; NaV channels; Nanomedicine; Pain; VGSCs; Voltage gated sodium channels.

Publication types

  • Review

MeSH terms

  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / pharmacokinetics
  • Anesthetics, Local / therapeutic use
  • Animals
  • Humans
  • Nanomedicine*
  • Pain / drug therapy
  • Pain Management* / methods
  • Voltage-Gated Sodium Channel Blockers* / administration & dosage
  • Voltage-Gated Sodium Channel Blockers* / pharmacokinetics
  • Voltage-Gated Sodium Channel Blockers* / therapeutic use
  • Voltage-Gated Sodium Channels / metabolism

Substances

  • Voltage-Gated Sodium Channel Blockers
  • Voltage-Gated Sodium Channels
  • Anesthetics, Local