# Birth Tissue Products for Non-opioid Treatment of Post-surgical Pain

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $660,845

## Abstract

PROJECT SUMMARY
Post-surgical pain causes significant suffering to patients and an over-reliance on opioids for pain reduction.
However, opioid analgesics cause severe side effects and a risk of accidental death from overdose.
Unfortunately, effective non-opioid pain therapy remains lacking. We aim to determine if human cell and
tissue product (HCT/P), such as amniotic membrane and umbilical cord, can be developed for use as a novel
and safe treatment of post-surgical pain. In Aim 1, we will first prove the concept by demonstrating the
efficacy, receptor mechanisms, and safety of HCT/P for inhibiting post-surgical pain in murine models. Our
preliminary studies showed that intraoperative treatment with HCT/P reduced the development of
post-surgical pain in rats. In Aim 2, we will demonstrate that HCT/P targets immune cells as an indirect mode
of anti-pain action. We hypothesize that HCT/P promotes regenerative wound healing by suppressing
immune cell recruitment and inducing anti-inflammatory effects. Our recent studies suggested that the heavy
chain-hyaluronic acid-pentraxin 3 complex (HC-HA/PTX3) is a biologically active component uniquely
present in HCT/P. We will further explore how HC-HA/PTX3 polarizes macrophages differentiated from
human THP-1 cells to an M2 phenotype and whether HC-HA/PTX3 inhibits the activation of human LAD2
mast cell and release of pro-inflammatory cytokines. In Aim 3, we will examine the targeting of primary
sensory neurons as the direct mode of anti-pain action by HCT/P and HC-HA/PTX3. We will test whether
HC-HA/PTX3 reduces intrinsic membrane excitability and inhibits membrane ion channels in dorsal root
ganglion neurons. Furthermore, we will investigate whether the neuronal inhibition by HC-HA/PTX3 involves
a novel mechanism that depends on CD44-mediated cytoskeletal rearrangement. To achieve these goals,
we will combine the expertise of preclinical and translational pain researchers from Johns Hopkins University
School of Medicine and the GMP manufacturing of HCT/P at TissueTech, Inc. This study will provide
important rationales for developing HCT/P-based bioceuticals as a viable non-opioid treatment of
post-surgical pain. Such drugs will act not only directly, by dampening neuronal excitation, but also indirectly,
by changing the wound environment and orchestrating regenerative healing. Through the complementary
dual mode of action, we envision that birth HCT/P may lead to an optimal therapeutic effect with lasting pain
relief and a potential “cure” of post-surgical pain.

## Key facts

- **NIH application ID:** 10026707
- **Project number:** 1R01NS117761-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Yun Guan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $660,845
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026707

## Citation

> US National Institutes of Health, RePORTER application 10026707, Birth Tissue Products for Non-opioid Treatment of Post-surgical Pain (1R01NS117761-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10026707. Licensed CC0.

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