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Updated: Apr 20, 2026
Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts
Brian J Wainger1, Elizabeth D Buttermore2, Julia T Oliveira3
11] F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Stem Cell Institute, Cambridge, Massachusetts, USA. [2] Department of Anesthesia, Critical Care and Pain Medicine and Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA. [3] Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
Scientists reprogrammed fibroblasts into nociceptor neurons using five transcription factors. These disease-specific neurons model pain hypersensitivity and neuropathy, offering new insights into human genetic disorders.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Somatic cell reprogramming generates specific neurons for disease modeling.
- Patient-derived neurons must capture neuronal diversity and disease pathophysiology.
Purpose of the Study:
- To identify transcription factors for reprogramming fibroblasts into nociceptor neurons.
- To model disease mechanisms underlying pain hypersensitivity and neuropathy.
Main Methods:
- Reprogramming mouse and human fibroblasts using five identified transcription factors.
- Analyzing expression of nociceptor-specific receptors and channels.
- Assessing TrpV1 sensitization in derived neurons.
Main Results:
- Successfully reprogrammed fibroblasts into nociceptor neurons.
- Derived neurons recapitulated native nociceptor subtype diversity and functional receptors.
- Demonstrated TrpV1 sensitization to inflammatory mediators and chemotherapy drugs.
- Revealed novel disease phenotypes in vitro using familial dysautonomia patient fibroblasts.
Conclusions:
- Five transcription factors can generate functional nociceptor neurons from fibroblasts.
- This method models key aspects of pain pathophysiology and neuropathy.
- Enables in vitro study of human genetic disease mechanisms.
