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Updated: Sep 1, 2025
04:59
Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors
Published on: September 27, 2019
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An LPAR -antagonist that reduces nociception and increases pruriception
Jacqueline Langedijk1, Erika Ivanna Araya2, Amanda Ribeiro Barroso2
1Amsterdam University Medical Centers (UMC), Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, Research Institute Amsterdam Gastroenterology, Endocrinology and Metabolism (AG&M), Amsterdam, Netherlands.
Frontiers in Pain Research (Lausanne, Switzerland)
|August 12, 2022
Summary
Compound 3 (cpd3) reduces pain signaling in mice but unexpectedly causes scratching, potentially by activating TRPA1 and other itch receptors. Further screening is needed for pain relief drugs.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Lysophosphatidic acid receptor 5 (LPAR5) is crucial for pain and itch signaling.
- Compound 3 (cpd3) is an LPAR5 antagonist investigated for its effects on these pathways.
Purpose of the Study:
- To evaluate the in vitro and in vivo effects of cpd3 on pain and itch signaling.
- To determine the role of TRPA1 in cpd3-induced effects.
Main Methods:
- Nociceptive behavior was induced by formalin, carrageenan, or prostaglandin E2 (PGE2) in mice.
- Scratch activity was measured in wild-type, phospholipase A2-overexpressing, and TRPA1-deficient mice.
- In vitro studies involved measuring intracellular calcium release in HMC-1 and HEK-TRPA1 cells.
Main Results:
- Cpd3 significantly reduced nociceptive behavior induced by various stimuli.
- Unexpectedly, cpd3 administration increased scratch activity in mice.
- In vitro, cpd3 triggered calcium release in HEK-TRPA1 cells, which was blocked by a TRPA1 antagonist, but scratch activity in TRPA1-deficient mice was not reduced.
Conclusions:
- Cpd3 exhibits in vivo antinociceptive effects but also induces scratching, likely via TRPA1 and other pruriceptors.
- These findings highlight the necessity of screening antinociceptive drug candidates for potential activity on pruriceptors.
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