An approach to targeting Nav1.7 for pain sensations
Theodore R. Cummins
Theodore R. Cummins
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Commentary

An approach to targeting Nav1.7 for pain sensations

Abstract

Pain is a serious medical condition with current treatments remaining limited by side effects. The Nav1.7 voltage-gated sodium channel is a crucial determinant of nociceptor excitability and a promising target for nonaddictive analgesics. However, development of blockers has been difficult. In this issue of the JCI, Singh, Bernabucci, and authors identify a strategy for reducing Nav1.7 currents. These findings identify fibroblast growth factor 13 (FGF13), a homologous factor distinct from typical growth factors (also known as FHF2B), which ramps up Nav1.7, nociceptor excitability, and pain. Compound PW164 was identified as a selective FGF13-Nav1.7 attenuator with analgesic activity. These findings highlight the power of targeting intrinsic modulators of Nav1.7 for pain management.

Authors

Theodore R. Cummins

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Figure 1

PW164 inhibits pain hypersensitivity.

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PW164 inhibits pain hypersensitivity. (A) Nav1.7 channels are expressed ...
(A) Nav1.7 channels are expressed in nociceptor neurons along with FGF13 (FHF2B), Nav1.8, and the capsaicin receptor TrpV1. (B) Noxious stimuli and painful conditions enhance Nav1.7 surface expression and pain hypersensitivity by increasing the interaction between FGF13 and Nav1.7. (C) PW164 binding to FGF13 prevents the increase in Nav1.7 currents, inhibiting nociceptor activity and reducing pain.