Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts.

Nat Neurosci
Authors
Keywords
Abstract

Reprogramming somatic cells from one cell fate to another can generate specific neurons suitable for disease modeling. To maximize the utility of patient-derived neurons, they must model not only disease-relevant cell classes, but also the diversity of neuronal subtypes found in vivo and the pathophysiological changes that underlie specific clinical diseases. We identified five transcription factors that reprogram mouse and human fibroblasts into noxious stimulus-detecting (nociceptor) neurons. These recapitulated the expression of quintessential nociceptor-specific functional receptors and channels found in adult mouse nociceptor neurons, as well as native subtype diversity. Moreover, the derived nociceptor neurons exhibited TrpV1 sensitization to the inflammatory mediator prostaglandin E2 and the chemotherapeutic drug oxaliplatin, modeling the inherent mechanisms underlying inflammatory pain hypersensitivity and painful chemotherapy-induced neuropathy. Using fibroblasts from patients with familial dysautonomia (hereditary sensory and autonomic neuropathy type III), we found that the technique was able to reveal previously unknown aspects of human disease phenotypes in vitro.

Year of Publication
2015
Journal
Nat Neurosci
Volume
18
Issue
1
Pages
17-24
Date Published
2015 Jan
ISSN
1546-1726
URL
DOI
10.1038/nn.3886
PubMed ID
25420066
PubMed Central ID
PMC4429606
Links
Grant list
1K08-NS082364 / NS / NINDS NIH HHS / United States
Howard Hughes Medical Institute / United States
NS038253 / NS / NINDS NIH HHS / United States
R01 NS038253 / NS / NINDS NIH HHS / United States
K08 NS082364 / NS / NINDS NIH HHS / United States
T32 GM07592 / GM / NIGMS NIH HHS / United States
R00 NS077435 / NS / NINDS NIH HHS / United States