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Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
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  1. Home
  3. Research Domains
  5. Environmental Sciences
  7. Ecological Applications
  9. Ecosystem Services (incl. Pollination)
  11. Phlorotannins From Edible Marine Seaweed Ecklonia Stolonifera Disrupt Usp5-cav3.2 Calcium Channel Interactions And Reverse Chronic Inflammatory Pain.
  1. Home
  3. Research Domains
  5. Environmental Sciences
  7. Ecological Applications
  9. Ecosystem Services (incl. Pollination)
  11. Phlorotannins From Edible Marine Seaweed Ecklonia Stolonifera Disrupt Usp5-cav3.2 Calcium Channel Interactions And Reverse Chronic Inflammatory Pain.

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Phlorotannins from edible marine seaweed Ecklonia stolonifera disrupt USP5-Cav3.2 calcium channel interactions and reverse chronic inflammatory pain.

Md Yousof Ali1, Vinicius M Gadotti2, Flavia T T Antunes3

  • 1Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N4N1, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N4N1, Canada; Zymedyne Therapeutics, Calgary, AB T2N4G4, Canada.

Toxicology and Applied Pharmacology
|June 12, 2025

View abstract on PubMed

Summary
This summary is machine-generated.

Phlorotannins from edible seaweed, phlorofucofuroeckol A (PFFA) and dieckol, show potential as novel analgesics. They block USP5 and Cav3.2 T-type calcium channel interactions, reducing pain behaviors in mice.

Keywords:
Cav3.2 III − IV Linker, USP5, Molecular DockingChronic Inflammatory PainPhlorofucofuroeckol aPhlorotannins

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Area of Science:

  • Pharmacology
  • Marine Natural Products
  • Pain Research

Background:

  • Ecklonia stolonifera seaweed contains phlorotannins with diverse pharmacologic effects.
  • Cav3.2 T-type calcium channels are identified as a unique molecular target for pain.
  • USP5 deubiquitinase interaction with Cav3.2 channels is a novel pathway in pain modulation.

Purpose of the Study:

  • To investigate the analgesic potential of phlorotannins PFFA and dieckol.
  • To determine if PFFA and dieckol block the USP5-Cav3.2 interaction.
  • To evaluate the role of Cav3.2 channels in the analgesic effects of these compounds.

Main Methods:

  • Administration of PFFA and dieckol via intrathecal or intragastric routes in mouse pain models.
  • Assessment of formalin-induced nocifensive behaviors and thermal hyperalgesia.
Seaweed
  • Evaluation of analgesic effects in Cav3.2 null mice.

    • Main Results:

    • PFFA and dieckol inhibited both phases of formalin-induced pain and reduced thermal hyperalgesia.
    • Dieckol's analgesic effects were lost in Cav3.2 null mice, but PFFA's were not.
    • These findings suggest Cav3.2 channels are essential for dieckol but not PFFA's in vivo actions.

    Conclusions:

    • Phlorotannins PFFA and dieckol effectively reduce pain and hyperalgesia in mouse models.
    • PFFA and dieckol represent a novel class of analgesics targeting the Cav3.2/USP5 interaction.
    • Edible marine seaweeds are a promising source for developing new pain therapeutics.