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Updated: Sep 30, 2025
Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors
Published on: September 27, 2019
Mitochondrial Reactive Oxygen Species Elicit Acute and Chronic Itch via Transient Receptor Potential Canonical 3
Seong-Ah Kim1, Jun Ho Jang1, Wheedong Kim2
1Department of Neurobiology and Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, 03080, Republic of Korea.
Abstract:
Mitochondrial reactive oxygen species (mROS) that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities. Here, we explored whether mROS overproduction induces itch through transient receptor potential canonical 3 (TRPC3), which is sensitive to ROS. Intradermal injection of antimycin A (AA), a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction, produced robust scratching behavior in naïve mice, which was suppressed by MitoTEMPO, a mitochondria-selective ROS scavenger, and Pyr10, a TRPC3-specific blocker, but not by blockers of TRPA1 or TRPV1. AA activated subsets of trigeminal ganglion neurons and also induced inward currents, which were blocked by MitoTEMPO and Pyr10. Besides, dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10, and also by resveratrol, an antioxidant. Taken together, our results suggest that mROS elicit itch through TRPC3, which may underlie chronic itch, representing a potential therapeutic target for chronic itch.
Insights
Mitochondrial reactive oxygen species (mROS) overproduction can cause itch by activating TRPC3 channels. This discovery highlights TRPC3 as a potential therapeutic target for chronic itch conditions.
Area of Science:
- Neuroscience
- Biochemistry
- Dermatology
Background:
- Mitochondrial dysfunction leads to overproduction of mitochondrial reactive oxygen species (mROS).
- mROS are implicated in various pathological conditions, including sensory abnormalities.
- The role of mROS in itch sensation, particularly via TRPC3 channels, requires further investigation.
Purpose of the Study:
- To investigate whether mROS overproduction induces itch through the ROS-sensitive TRPC3 channel.
- To explore the potential of TRPC3 as a therapeutic target for chronic itch.
Main Methods:
- Inducing mROS overproduction in mice using antimycin A (AA).
- Assessing scratching behavior and neuronal activation in response to AA.
- Utilizing TRPC3, TRPA1, and TRPV1 blockers, along with ROS scavengers (MitoTEMPO) and antioxidants (resveratrol).
- Examining AA-induced inward currents in trigeminal ganglion neurons.
Main Results:
- Intradermal injection of AA induced significant scratching behavior in mice.
- Scratching behavior and neuronal activation were suppressed by MitoTEMPO and a TRPC3 blocker (Pyr10), but not by TRPA1 or TRPV1 blockers.
- AA-induced inward currents in neurons were blocked by MitoTEMPO and Pyr10.
- Dry skin-induced chronic scratching was alleviated by MitoTEMPO, Pyr10, and resveratrol.
Conclusions:
- mROS overproduction elicits itch sensation through the activation of TRPC3 channels.
- TRPC3 plays a critical role in mediating mROS-induced itch.
- Targeting mROS and TRPC3 presents a promising therapeutic strategy for managing chronic itch.
