iPSCs and DRGs: stepping stones to new pain therapies.

Matthew Alsaloum, Stephen G Waxman

Journal: Trends in molecular medicine 2022;28(2):110-122

PMID: 34933815

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Abstract

There is a pressing need for more effective nonaddictive treatment options for pain. Pain signals are transmitted from the periphery into the spinal cord via dorsal root ganglion (DRG) neurons, whose excitability is driven by voltage-gated sodium (Na_V) channels. Three Na_V channels (Na_V1.7, Na_V1.8, and Na_V1.9), preferentially expressed in DRG neurons, play important roles in pain signaling in humans. Blockade of these channels may provide a novel approach to the treatment of pain, but clinical translation of preclinical results has been challenging, in part due to differences between rodent and human DRG neurons. Human DRG neurons and iPSC-derived sensory neurons (iPSC-SNs) provide new preclinical platforms that may facilitate the development of novel pain therapeutics.

Address: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; Center for Neuroscience & Regeneration Research, Yale University, West Haven, CT, USA; Center for Rehabilitation Research, VA Connecticut Healthcare System, West Haven, CT, USA; Yale Medical Scientist Training Program, Yale School of Medicine, New Haven, CT, USA; Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT, USA.; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; Center for Neuroscience & Regeneration Research, Yale University, West Haven, CT, USA; Center for Rehabilitation Research, VA Connecticut Healthcare System, West Haven, CT, USA. Electronic address: [email protected].

DOI: 10.1016/j.molmed.2021.11.005

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MeSH Terms: Diagnosis-Related Groups, Ganglia, Spinal, Humans, Induced Pluripotent Stem Cells, Neurons, Pain