# FABP5: Novel functions in pain modulation

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $493,279

## Abstract

Project Summary
Chronic pain is widespread in the adult population and inadequate pain control has a major negative impact on
the quality of life of chronic pain sufferers. Many currently available analgesics display modest efficacy and in
the case of opioids, addiction liability that has resulted in a dramatic increase in opioid abuse and addiction.
Consequently, there is an urgent need to identify novel targets for the development of non-opioid analgesics to
treat chronic pain. Our group has previously identified fatty acid binding protein 5 (FABP5) as an intracellular
carrier for endocannabinoids and structurally related N-acylethanolamines, whose inhibition augments tissue
levels of both lipid classes and produces analgesia. In the periphery, FABP5 inhibition additionally blunts the
release of pro-inflammatory and proalgesic mediators, positioning FABP5 as a promising target for the
development of analgesics. Accordingly, recently developed FABP5 inhibitors display efficacy in a range of pain
models and are rapidly advancing across the preclinical pipeline, with clinical testing scheduled to begin within
several years. Despite the therapeutic potential of FABP5 inhibition in treating pain, our understanding of its
mechanisms of action remains limited. While the majority of FABP5's effects originate from the modulation of
intracellular lipid transport and receptor activation, emerging evidence indicates that subsets of FABPs can be
released from distinct cell populations under specific conditions to exert unique biological functions. In this
application we test the novel hypothesis that inflammation triggers FABP5 secretion, which is instrumental in
delivering proalgesic lipids to nociceptive sensory neurons to maintain hyperalgesia. Conversely, sequestration
of extracellular FABP5 produces antinociceptive effects. Mechanistically, we hypothesize that FABP5 binds to
and delivers a lipid of the leukotriene family to its receptor, in turn sensitizing the nociceptive channels transient
receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) to sustain pain. Specific
Aim 1 tests the hypothesis that extracellular FABP5 modulates inflammatory pain hypersensitivity and will
interrogate the mechanisms underlying its cellular secretion. Specific Aim 2 tests the hypothesis that inhibition
of extracellular FABP5 or leukotriene signaling blunts inflammatory TRPA1 and TRPV1 sensitization. Specific
Aim 3 seeks to characterize the mechanisms underlying leukotriene-mediated TRPA1 sensitization. Successful
completion of the outlined aims will establish a novel paradigm linking extracellular FABP5 to pain modulation
and will provide a foundation for the development of analgesics targeting FABP5.

## Key facts

- **NIH application ID:** 10904429
- **Project number:** 1R01NS137595-01
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Martin Kaczocha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $493,279
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904429

## Citation

> US National Institutes of Health, RePORTER application 10904429, FABP5: Novel functions in pain modulation (1R01NS137595-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10904429. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*