iPSCs and DRGs: Steppingstones to New Pain Therapies

Trends Mol Med, 2022 · DOI: 10.1016/j.molmed.2021.11.005 · Published: February 1, 2022

Regenerative Medicine Neurology Pain Management

Simple Explanation

Chronic pain is a significant global issue, impacting quality of life and resulting in high healthcare costs. Current treatments are often inadequate and can lead to addiction, underscoring the necessity for innovative, non-addictive pain relief solutions. Dorsal root ganglion (DRG) neurons play a crucial role in transmitting pain signals. Voltage-gated sodium (NaV) channels, particularly NaV1.7, NaV1.8, and NaV1.9, which are highly expressed in DRG neurons, are key contributors to pain signaling. Human DRG neurons and induced pluripotent stem cell-derived sensory neurons (iPSC-SNs) are emerging as valuable preclinical tools. These platforms allow for more accurate modeling of human pain mechanisms and facilitate the development of targeted pain therapeutics.

Study Duration

Not specified

Participants

Human DRG neurons and induced pluripotent stem cell-derived sensory neurons (iPSCSNs)

Evidence Level

Not specified

Key Findings

1
Human and rodent DRG neurons exhibit significant functional and physiological differences, particularly in sodium channel composition and action potential properties, suggesting human DRG neurons may be a more clinically relevant model for pain studies.
2
iPSC-SNs can replicate human disease states and interindividual differences in pain phenotypes, making them useful for assessing pharmaceutical compounds and predicting drug responses in patients with chronic pain.
3
iPSC-SNs can be used to study the neurotoxic effects of chemotherapeutics and to identify potential therapeutic targets for pain management, as demonstrated by studies on chemotherapy-induced peripheral neuropathy (CIPN).

Research Summary

The development of new therapies for pain treatment is challenging, but human DRG neurons and iPSC-SNs offer promise. These systems more closely mimic human physiology compared to rodent DRG neurons and HEK293 cells. Human DRG neurons and iPSC-SNs have demonstrated the ability to replicate human diseases, including inter-individual differences, and show potential in assessing pharmaceutical compounds. Challenges remain in the usability and translation of preclinical data from these systems. These include difficulty in acquiring human DRG neurons and the time and financial investment required for iPSC-SN differentiation.

Practical Implications

Improved Preclinical Models

Using human DRG neurons and iPSC-SNs can lead to more accurate preclinical models for pain research, reducing the translational gap between preclinical studies and clinical trials.

Personalized Medicine

iPSC-SNs enable personalized medicine approaches by allowing researchers to study patient-specific pain mechanisms and predict individual drug responses, optimizing treatment strategies.

Drug Development

These platforms can facilitate the development of novel pain therapeutics by providing a more relevant system for assessing drug effectiveness, specificity, and potential side effects.

Study Limitations

1
Limited availability of human DRG neurons.
2
Long differentiation protocols for iPSC-SNs.
3
Questions regarding the maturity and representation of ion channels in iPSC-SNs.

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