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

NaV1.7 as a Pharmacogenomic Target for Pain: Moving Toward Precision Medicine.

Author information

1
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy, and Purdue Institute for Integrative Neuroscience, West Lafayette, IN 47907, USA.
2
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA.
3
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA; Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA. Electronic address: stephen.waxman@yale.edu.

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.

PMID:
29370938
DOI:
10.1016/j.tips.2017.11.010
[Indexed for MEDLINE]

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