# Evaluation of 6SHG/EM1 as a treatment for spinal cord injury-induced neuropathic pain in a pig model

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2023 · —

## Abstract

Project Summary:
The goal of this research is to validate a novel treatment for neuropathic pain after spinal cord injury (SCI-NP)
using a novel and highly clinically-relevant pig model. This research is innovative as we will validate exciting
new findings from research in rodents which discovered a highly efficacious treatment for SCI-NP in a clinically-
relevant pig model. Specifically, the new therapy involves delivering a gene construct encoding 6 copies of the
NMDA antagonist serine-histrogranin and 1 copy of the opioid agonist endomorphin 1 (6SHG/EM1) via
intraspinal delivery as detailed in Jergova et al., 2017. Indeed in the study to be validated, rats with the
6SHG/EM1 gene therapy did not exhibit a return of allodynia for the duration of the study (12 weeks). Data also
showed that the effects of 6SHG/EM1 were transiently blocked by intrathecal injection of anti-SHG and naloxone,
suggesting that the effects were due to "on-target" mechanisms. The expression of the transgenes in the spinal
cord was confirmed in neuronal cells near and around the dorsal horn in the vicinity of the injection location
(Jergova et al., 2017). To accelerate translation of this new therapy, we have back-translated quantitative
sensory testing (QST) methods used in human medicine to evaluate neuropathic pain for use in pigs. In
conjunction with QST testing, we have also developed a pig pain scale that includes both reflexive and
supraspinal responses, critically important for translation in pain research. We will employ a collaborative
approach to test the overarching hypothesis that administration of 6SHG/EM1 after SCI ameliorates SCI-NP in
a highly clinically-relevant pig model which closely mimics human SCI. Our goal is to optimize and scale-up this
highly efficacious SCI-NP treatment by using a clinically-relevant pig model to define key variables needed for
successful translation. We will test our overarching hypothesis and achieve these translational goals by
accomplishing three specific aims. In aim 1 we will optimize the methodology for successful delivery of AAV
gene therapy to the spinal cord after SCI in a pig model. In aim 2 we will test the hypothesis that post-SCI
administration of 6SHG/EM1 in the sub-acute period after SCI will ameliorate SCI-NP in a pig model. The SCI
model will be a midthoracic contusion/compression injury in pigs that is well established in our research
laboratory and as well as used by others. Baseline quantitative sensory testing (QST) over multiple dermatomes
will be conducted. QST includes assessments of thermal (hot and cold), tactile, pressure, and dynamic stimuli.
Pain responses will be scored on the porcine evoked pain scale that we developed which includes both supra-
spinal (affective) and spinal (reflexive) components. At weeks 6 after SCI (a time point when neuropathic pain
is developed), pigs will receive intraspinal injection of 6SHG/EM1 construct in adeno-associated virus (AAV).
Motor and QST responses will be eva...

## Key facts

- **NIH application ID:** 10935563
- **Project number:** 7I01BX005203-03
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** CANDACE L. FLOYD
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 7
- **Project period:** 2021-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935563

## Citation

> US National Institutes of Health, RePORTER application 10935563, Evaluation of 6SHG/EM1 as a treatment for spinal cord injury-induced neuropathic pain in a pig model (7I01BX005203-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10935563. Licensed CC0.

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