# Translational development of FDA-approved COX and LOX inhibitors to treat spinal cord injury-induced neuropathic pain.

> **NIH VA I01** · G V SONNY MONTGOMERY VA MEDCIAL CENTER · 2020 · —

## Abstract

Project Summary/Abstract: Spinal cord injury (SCI) produces a permanent loss of function below the level of
damage. In addition, more than 80% of SCI patients report the development of horribly debilitating neuropathic
pain (NP) that further robs the individual of life quality. NP can be an almost constant pathological companion
for these individuals and represents a significant cause of suicide in the chronic SCI population. Unfortunately,
there are few therapeutic options available to treat NP with a low percentage of individuals reporting treatment
efficacy. One possible explanation for the low number of effective treatment options is our poor understanding
of the mechanisms that initiate and potentially maintain NP in chronic SCI. Inflammation represents one possible
mechanism to elicit NP in the days to weeks following SCI. However, inflammation has previously been
considered to be transient, with mechanisms maintaining chronic NP unclear. Our published research suggests,
however, that inflammation can be detected long after the initial injury in a clinically-relevant model of rat SCI.
We detect the presence of inflammatory metabolites of arachidonic acid, particularly prostaglandins and
leukotrienes, produced by cyclooxygenase and lipoxygenase enzymes, respectively. FDA-approved non-steroidal
inflammatory (NSAIDs) drugs such as ibuprofen have been tried as analgesics for SCI-NP, but are ineffective.
Our detection of elevated intraspinal prostaglandins AND leukotrienes suggests a possible explanation for the
failure of “over the counter” NSAIDs in treating NP. Studies have shown that the targeting of only one metabolic
pathway, for instance, the cyclooxygenase pathway that generates prostaglandins, results in a “shunting” of the
arachidonic acid into the sister lipoxygenase pathway that produced leukotrienes; the end result being a net “gain”
of pro-inflammatory mediators (in this specific example, increased leukotrienes). We demonstrated that delayed
treatment with a novel dual inhibitor of both cyclooxygenase AND 5-lipoxygenase enzymes successfully reduced
NP in rats with chronic SCI. We subsequently demonstrated that this experimental drug reduced both
prostaglandins and leukotrienes if administered in the acute phase of injury, resulting in significant locomotor
recovery. Unfortunately, this drug is not FDA-approved. Our current goal is to test combinations of FDA-
approved inhibitors of cyclooxygenase AND 5-lipoxygenase to determine: 1) if combinations of these two classes
of inhibitors are as effective at treating or permanently blocking chronic NP as the previously tested experimental
dual-inhibitory drug, and 2) whether such treatment resolves the chronic pro-inflammatory state as evidenced by
reduced prostaglandin and leukotriene biosynthesis. As the FDA-approval process can require decades to move
a drug from bench to bedside, the effective translation of already-FDA-approved drugs to new tasks, such as the
treatment of neuropathic...

## Key facts

- **NIH application ID:** 9867617
- **Project number:** 5I01BX004170-03
- **Recipient organization:** G V SONNY MONTGOMERY VA MEDCIAL CENTER
- **Principal Investigator:** FEDERICO GONZALEZ-FERNANDEZ
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9867617

## Citation

> US National Institutes of Health, RePORTER application 9867617, Translational development of FDA-approved COX and LOX inhibitors to treat spinal cord injury-induced neuropathic pain. (5I01BX004170-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9867617. Licensed CC0.

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