# FABPs: Novel Roles in Pain and Inflammation

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $395,451

## Abstract

Chronic pain affects one third of the adult population and presents a massive societal and economic burden.
Current treatment approaches typically include non-steroidal anti-inflammatory drugs that suffer from limited
efficacy and opioids, which possess significant addiction liability. Consequently, there is an urgent need to
identify novel drug targets to facilitate the development of non-addictive analgesics to treat chronic pain. The
endocannabinoid anandamide (AEA) activates cannabinoid receptors while the related lipid
palmitoylethanolamide (PEA) serves as an agonist at peroxisome proliferator-activated receptor alpha (PPARα).
Activation of cannabinoid receptors by AEA or PPARα receptors by PEA reduces pain, thus positioning
modulation of AEA and PEA signaling as an attractive strategy for the development of analgesics. Our group
recently identified fatty acid binding protein 5 (FABP5) as an intracellular carrier for AEA and PEA, whose
inhibition elevates AEA and PEA levels and produces analgesia. In addition to its expression in the brain, FABP5
is enriched in peripheral sensory neurons and macrophages, positioning it in cell populations that promote pain.
Transient receptor potential vanilloid receptor 1 (TRPV1) is an ion channel expressed in peripheral sensory
neurons that is essential for inflammatory thermal hyperalgesia and is implicated in diverse pain conditions in
humans. Here, we will test the novel hypothesis that FABP5 inhibition potentiates AEA and PEA signaling in
sensory neurons to suppress pain by attenuating the sensitization and upregulation of TRPV1 during
inflammation. Specific Aim 1 will test the hypothesis that genetic deletion of FABP5 in sensory neurons unmasks
analgesic effects mediated by AEA and PEA while its deletion in macrophages suppresses pain by attenuating
the pro-inflammatory output of macrophages. To interrogate the mechanisms underlying these effects, Specific
Aim 2 will test the hypothesis that TRPV1 sensitization, a process that amplifies inflammatory pain, is suppressed
in mice lacking FABP5. We will further determine whether this effect is mediated by augmented AEA and PEA
signaling in sensory neurons. Specific Aim 3 will test the hypothesis that FABP5 is essential for TRPV1
upregulation during chronic inflammation. Specifically, we will investigate the molecular mechanisms underlying
the control of TRPV1 upregulation by FABP5 in sensory neurons. If successful, the outcome of this work will
advance our understanding of pain modulation by FABP5, AEA, and PEA, and will provide a foundation for the
development of analgesics targeting FABP5.

## Key facts

- **NIH application ID:** 10169397
- **Project number:** 5R01DA035949-07
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Martin Kaczocha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $395,451
- **Award type:** 5
- **Project period:** 2014-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169397

## Citation

> US National Institutes of Health, RePORTER application 10169397, FABPs: Novel Roles in Pain and Inflammation (5R01DA035949-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10169397. Licensed CC0.

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