# Lipoteichoic acid mediated modulation of chronic pain

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $540,730

## Abstract

Prostatitis accounts for 2 million outpatient visits per year in the United States, including
1% of those to primary care physicians. Chronic prostatitis/Chronic pelvic pain syndrome
(CP/CPPS) is clinically characterized by dysuria and pain in the perineum, testes, penis,
and suprapubic region. Despite CPPS accounting for 90% of all chronic prostatitis, there
is an absence of effective therapies. In animal models, the chronic pelvic pain is shown to
be associated with immune dysregulation and the activation of nociceptive pathways in
the peripheral and central nervous system. We previously demonstrated that a
commensal Staphylococcus epidermidis strain derived from the prostate of a healthy human
volunteer could be delivered intraurethrally to rapidly inhibit the pathogenic immune
response and lead to a profound amelioration of pelvic pain. In the last period of this
grant we isolated, purified, and recapitulated the anti-nociceptive effects using the
lipoteichoic acid (SELTA) component of the whole bacteria. We demonstrated
immunomodulatory activity through induced expression of checkpoint ligands PD-L1
and PD-L2. In preliminary studies in support of this application, we examined direct
effects of SELTA on dorsal root ganglia neurons and identified that SELTA is capable of
TLR2 dependent activation of a homeostatic neuronal pathway involved in pain
modulation. SELTA treatment was also demonstrated to increase expression of the
endogenous opioid pathway in neurons. We therefore hypothesize that SELTA can
mediate anti-nociceptive effects by modulation of neuronal excitability through activation
of homeostatic inhibitory signaling and induction of endogenous opioid pathways. In this
study we will dissect novel mechanisms underlying activation of these anti-nociceptive
pathways using a combination of animal models, ex vivo dorsal root ganglia slice
recordings and in vitro signaling studies. Proof of concept for SELTA activity will be
demonstrated in human dorsal root ganglia. The proposed studies will provide a
mechanistic understanding of how SELTA exerts anti-nociceptive activity and will set-
the-stage for its development as a novel cutting-edge therapeutic for chronic pelvic pain.

## Key facts

- **NIH application ID:** 10539502
- **Project number:** 2R01DK108127-05A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** PRAVEEN THUMBIKAT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $540,730
- **Award type:** 2
- **Project period:** 2016-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10539502

## Citation

> US National Institutes of Health, RePORTER application 10539502, Lipoteichoic acid mediated modulation of chronic pain (2R01DK108127-05A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10539502. Licensed CC0.

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