Na V 1.7 as a Pharmacogenomic Target for Pain: Moving Toward Precision Medicine

Trends Pharmacol Sci. 2018 Mar;39(3):258-275. doi: 10.1016/j.tips.2017.11.010. Epub 2018 Jan 20.

Abstract

Chronic pain is a global unmet medical need. Most existing treatments are only partially effective or have side effects that limit their use. Rapid progress in elucidating the contribution of specific genes, including those that encode peripheral voltage-gated sodium channels, to the pathobiology of chronic pain suggests that it may be possible to advance pain pharmacotherapy. Focusing on voltage-gated sodium channel NaV1.7 as an example, this article reviews recent progress in developing patient-specific induced pluripotent stem cells (iPSCs) and their differentiation into sensory neurons, together with advances in structural modeling, that have provided a basis for first-in-human translational studies. These new approaches will hopefully transform the treatment of pain from trial-and-error toward genomically guided, precision pharmacotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Molecular Targeted Therapy / methods*
  • NAV1.7 Voltage-Gated Sodium Channel / genetics*
  • NAV1.7 Voltage-Gated Sodium Channel / metabolism
  • Pain / drug therapy*
  • Pain / genetics
  • Pain / metabolism
  • Pharmacogenetics / methods*
  • Precision Medicine / methods*
  • Sodium Channel Blockers / pharmacology
  • Sodium Channel Blockers / therapeutic use

Substances

  • NAV1.7 Voltage-Gated Sodium Channel
  • Sodium Channel Blockers