# From Pain Resilience Genes Toward Therapeutic, Non-Opiate Modulation: An iPSC-Based Approach

> **NIH VA I21** · VA CONNECTICUT HEALTHCARE SYSTEM · 2023 · —

## Abstract

Safe and effective treatment for chronic pain is an unmet medical need, which in turn has contributed to the
opioid crisis. The experience of pain varies from person to person, with some individuals relatively resilient to
pain compared to others. Individual-to-individual variation in pain, while observed in the clinics, has not been
accurately modeled in the laboratory nor has its mechanistic underpinnings carefully examined. This is partially
because pain involves detection by the peripheral nervous system and perception in the central nervous
system, and may be modulated by many factors including genetic, epigenetic, environmental and social. Our
studies of blood relatives with inherited erythromelalgia (IEM) with varying degrees of pain despite carrying the
same Nav1.7 mutation (S241T) have allowed us to identify modulatory gene variants/mutations expressed in
sensory neurons using whole exome sequencing as modulators of pain in these patients. In this proposal, we
will build upon our discovery of “pain resilience genes” and evaluate the potential of pharmacological
modulators of Kv7 channels to reduce hyperexcitability of human sensory neurons derived from genetically
validated subjects with chronic pain, as a way to identify safe and effective strategies that steer away from
opioids in the treatment of chronic pain.

## Key facts

- **NIH application ID:** 10655583
- **Project number:** 5I21RX003860-02
- **Recipient organization:** VA CONNECTICUT HEALTHCARE SYSTEM
- **Principal Investigator:** Mark Estacion
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10655583

## Citation

> US National Institutes of Health, RePORTER application 10655583, From Pain Resilience Genes Toward Therapeutic, Non-Opiate Modulation: An iPSC-Based Approach (5I21RX003860-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10655583. Licensed CC0.

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