Itch relief concept: A soothing hand calms irritated skin, representing sumatriptan's effect on the nitric oxide pathway.

Itch Relief Breakthrough: Sumatriptan's Surprising Role in Soothing Skin

Mira Elwood in Health & Wellness December 2025 • 4 min read.

"New research reveals how a common migraine medication could hold the key to calming chronic itch, offering hope for those seeking alternative treatments."

Chronic itch, or pruritus, is more than just a nuisance; it's a debilitating symptom that significantly impacts the quality of life for many. Traditional treatments, like antihistamines, often fall short, leaving sufferers searching for effective relief. Scientists have been working hard to find out what causes itch in order to provide alternative treatments.

One area of growing interest is histamine-independent itch, which doesn't respond to common antihistamines. A common research model utilizes chloroquine (CQ) to induce itch. Recent studies suggest that nitric oxide (NO) plays a crucial role in this type of itch, making it a potential target for new therapies.

Now, a new study sheds light on the potential of sumatriptan, a medication commonly used to treat migraines and cluster headaches, in alleviating chloroquine-induced itch. The findings reveal its involvement in the nitric oxide pathway, offering a promising avenue for novel anti-itch treatments.

How Sumatriptan Calms the Itch: Targeting the Nitric Oxide Pathway

Itch relief concept: A soothing hand calms irritated skin, representing sumatriptan's effect on the nitric oxide pathway.

The research, led by Prof. Ahmad Reza Dehpour and colleagues, investigated the effect of sumatriptan on CQ-induced scratching in mice. They focused on the rostral back model of itch, where chloroquine is injected intradermally to trigger scratching behavior. The study evaluated how sumatriptan, alone and in combination with other compounds, affected this scratching.

Key findings from the study include:

Sumatriptan Reduces Scratching: Both intraperitoneal (IP) and intradermal (ID) administration of sumatriptan significantly reduced CQ-induced scratching in mice.
Reversal by GR-127935: The anti-pruritic effect of sumatriptan was reversed by GR-127935, a selective 5-HTR1b and 5-HTR1d antagonist, highlighting the involvement of these receptors.
Combined Action with L-NAME: Combining sub-effective doses of sumatriptan and L-NAME, a non-selective nitric oxide synthase inhibitor, further decreased scratching behavior.
Reduced Nitrite Levels: Sumatriptan significantly reduced intradermal nitrite levels, indicating its impact on the nitric oxide pathway.

These results suggest that sumatriptan suppresses CQ-induced itch by activating 5-HT1b/1d receptors and modulating the nitric oxide pathway in the skin. The activation of 5-HT1b/1d receptors is a key mechanism to alleviate the sensation of itch.

The Future of Itch Relief: New Therapeutic Targets

This research opens new avenues for developing targeted treatments for chronic itch. By understanding the role of sumatriptan and the nitric oxide pathway, scientists can explore new therapeutic interventions that provide more effective and lasting relief.

While the study focused on chloroquine-induced itch in mice, the findings have broader implications for understanding and treating other types of histamine-independent itch. Further research is needed to determine the effectiveness of triptans in treating pruritic diseases in humans.

The discovery may provide insight for development of new target therapeutics to treat CQ-induced itch as well as better understanding of pharmacological interaction of this phenomenon. However, the potency of drugs to reduce itch in human is difficult to be interpreted by mouse models due to species differences. Thus, further studies will be significant to clarify the role for triptans in pruritic diseases in humans.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1111/fcp.12317, Alternate LINK

Title: Pharmacological Evidence Of Involvement Of Nitric Oxide Pathway In Anti-Pruritic Effects Of Sumatriptan In Chloroquine-Induced Scratching In Mice

Subject: Pharmacology (medical)

Journal: Fundamental & Clinical Pharmacology

Publisher: Wiley

Authors: Nazgol-Sadat Haddadi, Sattar Ostadhadi, Saeed Shakiba, Khashayar Afshari, Nastaran Rahimi, Arash Foroutan, Ahmad-Reza Dehpour

Published: 2017-09-06

Everything You Need To Know

How does Sumatriptan potentially help with chronic itch?

Sumatriptan, a medication typically used for migraines, has been found to potentially alleviate chronic itch. It achieves this by interacting with the nitric oxide pathway, a biological process involved in the sensation of itch, specifically in the context of chloroquine-induced itch. This interaction offers a potential avenue for new treatments addressing chronic itch.

What role does chloroquine play in this research?

The study used chloroquine (CQ) to induce itch in mice, a common model for studying itch. Chloroquine triggers scratching behavior, allowing researchers to observe the effects of potential treatments. The researchers focused on the rostral back model of itch, where chloroquine is injected intradermally to trigger scratching behavior. This model is particularly relevant because it helps scientists understand itch that doesn't respond to antihistamines, a significant area of interest.

Why is the nitric oxide pathway important in this context?

The nitric oxide pathway is a key biological process involved in the sensation of itch, particularly in histamine-independent itch. Sumatriptan impacts this pathway, specifically by reducing intradermal nitrite levels. This modulation of the nitric oxide pathway is crucial because it suggests a potential mechanism for controlling itch, opening new possibilities for treatments. Scientists can explore new therapeutic interventions that provide more effective and lasting relief.

What is the significance of GR-127935 in the study?

GR-127935, a selective 5-HTR1b and 5-HTR1d antagonist, was used to test the role of certain receptors. When administered, it reversed the anti-itch effect of sumatriptan, indicating that these receptors (5-HTR1b and 5-HTR1d) are involved in sumatriptan's action. This highlights the importance of these receptors in the itch-relieving mechanism of Sumatriptan.

What were the key findings regarding Sumatriptan's effect on itch in the study?

The research indicates that sumatriptan can reduce chloroquine-induced scratching in mice. This effect was observed when sumatriptan was administered both intraperitoneally (IP) and intradermally (ID). Furthermore, combining sumatriptan with L-NAME, a nitric oxide synthase inhibitor, resulted in a further decrease in scratching behavior. These findings suggest that sumatriptan suppresses itch through its interaction with the nitric oxide pathway and the activation of 5-HT1b/1d receptors.