# Shaping Pain:The Pain Resilience Project

> **NIH VA I01** · VA CONNECTICUT HEALTHCARE SYSTEM · 2022 · —

## Abstract

Safe and effective treatment for pain remains a global 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 both 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 thus far 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, and indict one specific gene, KCNQ2, and
suggest three additional genes, as modulators of pain in these patients. There are undoubtedly additional
molecules that influence DRG neuron firing and modulate pain.
In this proposed work, we will capitalize on our unique platform of induced pluripotent stem cell technology,
and access to additional families with IEM and varying inter-individual pain profiles, to identify modulatory
genes that might be developed into targets for the development of new pain treatments.

## Key facts

- **NIH application ID:** 10228540
- **Project number:** 5I01RX003201-03
- **Recipient organization:** VA CONNECTICUT HEALTHCARE SYSTEM
- **Principal Investigator:** Stephen Waxman
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228540

## Citation

> US National Institutes of Health, RePORTER application 10228540, Shaping Pain:The Pain Resilience Project (5I01RX003201-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10228540. Licensed CC0.

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