Document Type

Poster

Original Publication Date

2025

Journal/Book/Conference Title

2025 Mid Atlantic Pharmacology Society Annual Meeting Conference

Date of Submission

November 2025

Abstract

Opioids remain one of the most effective treatment strategies for managing severe and persistent pain. However, its long-term use leads to pharmacological tolerance, requiring progressively higher doses to achieve analgesia. This dose escalation increases the risk of life-threatening side effects and dependence, underscoring the urgent need for safe adjuncts to preserve opioid efficacy. Emerging evidence suggests that morphine tolerance is linked to intestinal inflammation and disruption of gut barrier integrity. Broccoli Seed Extract (BSE), rich in the bioactive compound sulforaphane, exhibits antioxidant and anti-inflammatory properties that may protect against these effects. We hypothesized that BSE could prevent the development of morphine tolerance by mitigating inflammation associated with chronic opioid exposure. To test this, an animal model was used with three groups (n=20 each): saline, chronic morphine + vehicle, and chronic morphine + BSE. All animals received four days of respective treatments followed by a morphine dose-response challenge on day 5. Analgesic response was assessed using the tail immersion assay, and the animals which were administered BSE showed a rightward shift in the dose-response curve compared to morphine + vehicle group but the difference did not reach statistical significance. To further explore the anti-inflammatory mechanism, T84 colon epithelial cells were pre-treated with BSE for 3 hours prior to exposure to an “inflammatory colon soup” prepared from chronically morphine-treated animal colons. BSE pre-treatment reduced IL-8 mRNA expression in T84 cells. Although reduction of morphine tolerance with BSE did not reach statistical significance in-vivo, inhibition of proinflammatory cytokine IL-8 expression in colonic epithelial cells suggest that anti-inflammatory effects of BSE may be modulated by the shift in gut microbiome due to chronic morphine. Harnessing such natural compounds may provide a novel, accessible strategy to enhance opioid safety and maintain pain relief in chronic pain management.

Rights

© The Authors

Is Part Of

VCU Pharmacology and Toxicology Publications

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