Gain-of-function mutations in SCN9A, which encodes the sodium channel Nav1.7 (expressed in the peripheral nervous system), has a crucial role in a chronic pain disorder, inherited erythromelalgia (IEM). Here, Cao et al. demonstrate that iPSC-derived sensory neurons (iPSC-SNs), generated from four patients with IEM carrying different SCN9A mutations, exhibit elevated excitability and increased sensitivity to heat compared with iPSC-SNs from non-IEM donors. The increased excitability and sensitivity of these neurons were reduced by the novel selective Nav1.7 blocker PF-05089771. A single oral dose of PF-05089771 decreased heat-induced pain in 4 out of 5 patients with IEM.
References
Cao, L. et al. Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia. Sci. Trans. Med. 8, 335ra56 (2016)
Rights and permissions
About this article
Cite this article
Crunkhorn, S. Blocking pain in inherited erythromelalgia. Nat Rev Drug Discov 15, 384 (2016). https://doi.org/10.1038/nrd.2016.102
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrd.2016.102