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Updated: Jul 23, 2025

Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors
Published on: September 27, 2019
IL-33/ST2 signaling in pain and itch: Cellular and molecular mechanisms and therapeutic potentials
Peiyi Li1, Qing Yu1, Huimin Nie1
1Department of Neurobiology and Acupuncture Research, the Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, China.
Abstract:
Pain is a cardinal feature of many diseases. Chronic pain poses heavy burdens to the suffering patients, both physically and mentally. However, current mainstream medications for chronic pain, including opioids, antidepressants and non-steroid anti-inflammatory drugs are sometimes inefficient for chronic pain management and may cause side effects that limit long term usage. IL-33 belongs to IL-1 cytokine family and it exerts biological activities through binding to its specific receptor ST2. IL-33/ST2 signaling is very important in both innate and adaptive immunity. Emerging evidence indicates IL-33/ST2 signaling regulates pain in both immune and somatosensory systems through promoting neuro-immune or neuron-glia crosstalk, neuroinflammation and neuronal hyperexcitability. Some very latest studies indicate a vital part of IL-33/ST2 in mediating chronic itch. This work aims to overview the existing knowledge regarding the mechanisms of IL-33/ST2 involvement in pain and itch conditions, considering their potential similarities. We also summarized some key findings obtained from clinical studies. The targeting of IL-33/ST2 signaling holds promise for the development of novel therapeutic modalities in the management of pain and itch.
Insights
Interleukin-33 (IL-33) and its receptor ST2 are implicated in chronic pain and itch. Targeting this pathway offers potential new treatments for these debilitating conditions.
Area of Science:
- Immunology
- Neuroscience
- Pain Research
Background:
- Chronic pain significantly impacts patients physically and mentally.
- Current pain medications have limitations in efficacy and side effects.
- Interleukin-33 (IL-33), part of the IL-1 cytokine family, binds to its receptor ST2.
Purpose of the Study:
- To review the mechanisms of IL-33/ST2 signaling in pain and itch.
- To explore potential similarities between IL-33/ST2's role in pain and itch.
- To summarize clinical findings related to IL-33/ST2.
Main Methods:
- Literature review of existing knowledge on IL-33/ST2 in pain and itch.
- Analysis of studies investigating neuro-immune and neuron-glia crosstalk.
- Inclusion of findings from relevant clinical studies.
Main Results:
- IL-33/ST2 signaling regulates pain via neuroinflammation and neuronal hyperexcitability.
- Emerging evidence links IL-33/ST2 signaling to chronic itch.
- Clinical studies provide insights into the role of this pathway.
Conclusions:
- IL-33/ST2 signaling is a key regulator in pain and itch conditions.
- Targeting the IL-33/ST2 pathway presents a promising therapeutic strategy.
- Novel treatments for chronic pain and itch may emerge from modulating IL-33/ST2.
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