# Potential Application of Boldine in Alleviating SCI-induced Neuropathic Pain

> **NIH VA I21** · JAMES J PETERS VA  MEDICAL CENTER · 2020 · —

## Abstract

Spinal cord injury (SCI) affects over 291,000 Americans of whom ~47,000 are veterans. Providing high quality
care to veterans with SCI is a priority within the Department of Veterans Affairs. For SCI patients, pain is one of
the most difficult complications to treat, and this is especially true for neuropathic pain (NP) which is known to
be chronic and refractory to many currently available treatments. Until now, there has been no fully effective
therapy for neuropathic pain in SCI. Recent studies have shown that after nerve injury, Toll-like receptors (TLRs)
are involved in the generation of neuropathic pain. Our feasibility studies in primary astrocytes suggested that
boldine, a naturally occurring compound, could inhibit the TLR-inflammasome signaling. Pilot studies conducted
in a mouse model of moderate contusion SCI revealed that boldine improved locomotor function following SCI
and reduced the expression of major components of the TLR family and inflammasome complexes in brain
regions linked to pain processing. Based on these preliminary findings and the important role of toll-like receptors
and inflammasome complexes in neuropathic pain, we propose to conduct preclinical studies using sensory
functional outcome measurements and molecular mechanistic studies to test whether oral administration of
boldine will alleviate pain responses in a mouse model of SCI. Outcomes will support follow-up preclinical and
clinical translational studies for potential application of this natural compound in reducing neuropathic pain in
veterans with SCI.
Aim 1. Test the effect of boldine on regulating TLR and inflammasome pathways in primary cultures.
Rationale: TLRs are responsible for the stimulation of astrocytes and microglia and will induce expression in
these cells of proinflammatory mediators and cytokines, therefore leading to the generation and maintenance of
neuropathic pain. Our preliminary findings in mouse primary astrocyte cultures suggested that boldine treatment
significantly reduced the expression of some major components in the TLR-inflammasome pathways, including
TLR2, NFκB, Caspase-1 and IL-1β. Hypothesis: Boldine will inhibit TLR-inflammasome pathway in vitro.
Methods: Mouse primary astrocyte, microglia, dorsal horn and DRG cultures will be treated with LPS in the
presence or absence of 25 or 50 µg/ml boldine. Cytotoxicity will be determined by LDH assay. The mRNA and
protein levels for major components of the TLR-inflammasome will be determined by qPCR or western blot,
respectively. IL-1β level in the medium will be measured by ELISA, NFκB nuclear localization will be determined
by immunofluorescence, and Caspase-1 activity will also be measured.
Aim 2. Determine the effects of boldine on reducing neuropathic pain in a mouse model of moderate
severity contusion SCI and dissect possible mechanisms. Rationale: Spinal cord injuries in the mice have
been a widely used model to evaluate different experimental treatment strategies. Our prelimi...

## Key facts

- **NIH application ID:** 10120253
- **Project number:** 1I21RX003453-01A1
- **Recipient organization:** JAMES J PETERS VA  MEDICAL CENTER
- **Principal Investigator:** Wei Zhao
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120253

## Citation

> US National Institutes of Health, RePORTER application 10120253, Potential Application of Boldine in Alleviating SCI-induced Neuropathic Pain (1I21RX003453-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10120253. Licensed CC0.

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