Altered gating and expression of voltage-gated sodium channels (VGSCs) contribute to acute and chronic pain as well as inherited pain syndromes. Although much effort has been taken to understand underlying mechanisms and to develop new therapeutics, therapy is often dissatisfactory. One limitation of studying pain in patients is that nociceptive neurons as such can not be investigated on a cellular basis.

The aim of this study was to characterize the electrophysiological properties of human stem cell derived nociceptors that were obtained from human embryonic stem cells as described recently (Chambers et al. 2012, Nat. Biotech). Among the population of cells differentiated with this small-molecule inhibition protocol a subgroup of cells that resembled the morphology of mammalian dorsal root ganglia (DRGs) was further investigated.

Using the patch-clamp technique we found that >33% of the differentiated cells showed electrical activity either in terms of spikelets (12%) or in the generation of action potentials (24%). For 75% of these cells phasic firing was observed whereas 25% showed tonic firing. Among the ion channels expressed were VGSCs (11%), voltage-gated potassium channels (15%) or both in 52% of the investigated cells. Tetrodotoxin (TTX) resistant sodium currents, which are a hallmark of peripheral sensory neurons and nociceptors, were observed in about 60% of the tested cells.

Here we show that human embryonic stem cells can provide a useful tool to investigate ion channels in a patient derived cell system that may help to better understand the mechanisms underlying pain and offers the opportunity to test potential therapeutics in the future.