Stylized brain with fiber optic cables emitting blue light on areas of pain perception.

Shedding Light on Pain: How a Light-Activated Channel Offers New Hope for Chronic Pain Sufferers

Kai Mendoza in Health & Wellness August 2025 • 4 min read.

"Scientists develop BLINK2, a revolutionary light-gated potassium channel, for sustained neuronal inhibition and long-lasting pain relief without high light intensities."

Chronic pain affects millions worldwide, significantly impacting quality of life and placing a heavy burden on healthcare systems. Current treatments often fall short, leading researchers to explore innovative approaches for effective and sustained pain relief. One promising avenue is optogenetics, a technique that uses light to control neuronal activity.

While optogenetics has shown great potential, existing inhibitory tools have limitations, such as the need for high light intensities and short-lived effects. These drawbacks have spurred the development of new and improved optogenetic tools that can provide long-lasting inhibition with minimal light exposure. BLINK2 is an optimized blue-light-sensitive synthetic potassium channel.

BLINK2 offers a potential solution to the challenges of chronic pain management by providing sustained neuronal inhibition with low light intensities. Its unique properties and demonstrated effectiveness in preclinical models make it a promising candidate for future therapeutic applications. This article delves into the science behind BLINK2, its development, and its potential to revolutionize chronic pain treatment.

BLINK2: A New Frontier in Optogenetic Pain Relief

Stylized brain with fiber optic cables emitting blue light on areas of pain perception.

The limitations of existing inhibitory optogenetic tools, such as light-gated proton pumps and chloride pumps, have driven the search for more effective solutions. These tools often require high light intensities, which can cause tissue heating and damage, and their effects are typically short-lived. Anion-selective channelrhodopsins (ACRs) can provide longer inhibition, but their effectiveness depends on the chloride reversal potential, which varies among neurons. To overcome these challenges, researchers have focused on engineering light-gated potassium channels, which offer a more universal and reliable mechanism for neuronal inhibition.

BLINK2 is an optimized version of a previously engineered light-gated potassium channel called BLINK1. BLINK1, in which a LOV2 photoreceptor domain reversibly controls a K+ channel in response to blue light, has favorable properties for optogenetics, including a low light requirement and a large unitary conductance. However, BLINK1 has low surface expression, which limits its wider use. BLINK2 was developed to improve surface expression and enhance its effectiveness as an inhibitory tool.

To improve BLINK1 trafficking to the plasma membrane, researchers added C-terminal signal sequences that promote forward trafficking in eukaryotic K+ channels. They tested various endoplasmic reticulum export motifs and trafficking signals, including those from Kir2.1, TASK1-3, and KAT1, alone and in combination. After extensive experimentation, BLINK2 emerged as the most promising candidate, showing improved expression efficiency and robust light regulation, C-terminal signal sequences that promote forward trafficking in eukaryotic K+ channels.

Compared with BLINK1, BLINK2 shows higher surface expression in neurons and efficient inhibition of firing in animal models. BLINK2 exhibits post-illumination activity, lasting tens of minutes, which is advantageous for achieving long neuronal inhibition without toxic exposure to prolonged illumination. The ability to achieve long neuronal inhibition without toxic exposure to prolonged illumination makes BLINK2 an appealing therapeutic option.

Future Implications and Therapeutic Potential

BLINK2 represents a significant advancement in optogenetic tools for chronic pain management. Its ability to provide sustained neuronal inhibition with minimal light exposure makes it a promising candidate for future therapeutic applications. With further research and development, BLINK2 could revolutionize the treatment of chronic pain and improve the lives of millions of sufferers worldwide.

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This article is based on research published under:

DOI-LINK: 10.1038/s41592-018-0186-9, Alternate LINK

Title: A Light-Gated Potassium Channel For Sustained Neuronal Inhibition

Subject: Cell Biology

Journal: Nature Methods

Publisher: Springer Science and Business Media LLC

Authors: Laura Alberio, Andrea Locarno, Andrea Saponaro, Edoardo Romano, Valérie Bercier, Shahad Albadri, Federica Simeoni, Silvia Moleri, Silvia Pelucchi, Alessandro Porro, Elena Marcello, Noemi Barsotti, Kerri Kukovetz, Arjen J. Boender, Andrea Contestabile, Shizhen Luo, Aubin Moutal, Yingshi Ji, Giulia Romani, Monica Beltrame, Filippo Del Bene, Monica Di Luca, Rajesh Khanna, Henry M. Colecraft, Massimo Pasqualetti, Gerhard Thiel, Raffaella Tonini, Anna Moroni

Published: 2018-10-30

Everything You Need To Know

What is BLINK2 and how does it work to relieve chronic pain?

BLINK2 is a revolutionary light-gated potassium channel designed for optogenetics. It's activated by blue light to inhibit neuronal activity, specifically targeting pain signals. BLINK2 offers sustained neuronal inhibition, providing long-lasting pain relief without the need for high light intensities, which are often required by other optogenetic tools. This makes it a significant advancement in managing chronic pain by offering a more effective and less invasive approach compared to existing methods.

How does BLINK2 overcome the limitations of previous optogenetic tools?

Existing inhibitory optogenetic tools, such as light-gated proton pumps and chloride pumps, often require high light intensities that can cause tissue damage and have short-lived effects. Anion-selective channelrhodopsins (ACRs) offer longer inhibition but depend on the chloride reversal potential, which varies among neurons. BLINK2 overcomes these issues by functioning as a light-gated potassium channel. It requires only low light intensities to activate, minimizing potential tissue damage, and provides sustained neuronal inhibition for extended periods. BLINK2's improved surface expression and post-illumination activity offer significant advantages over earlier optogenetic tools.

What are the key improvements in BLINK2 compared to its predecessor, BLINK1?

While BLINK1 had favorable properties such as low light requirements and large unitary conductance, its low surface expression limited its wider use. BLINK2 was developed to enhance surface expression and overall effectiveness. Researchers added C-terminal signal sequences that promote forward trafficking in eukaryotic K+ channels, using motifs from Kir2.1, TASK1-3, and KAT1. This modification significantly improved BLINK2's surface expression in neurons, resulting in more efficient inhibition of firing in animal models and making it a more viable therapeutic option.

What implications does BLINK2 have for the future treatment of chronic pain?

BLINK2 represents a significant step forward in optogenetic tools for chronic pain management. Its ability to provide sustained neuronal inhibition with minimal light exposure offers a promising avenue for future therapeutic applications. The post-illumination activity, which lasts tens of minutes, is particularly advantageous for achieving long neuronal inhibition without toxic exposure to prolonged illumination. With further research and development, BLINK2 could potentially revolutionize chronic pain treatment, offering improved quality of life for millions of sufferers worldwide, by providing a more targeted and effective approach with fewer side effects compared to traditional treatments.

How was BLINK2 developed and optimized for better performance?

BLINK2's development focused on improving the surface expression of its predecessor, BLINK1. Researchers added C-terminal signal sequences that promote forward trafficking in eukaryotic K+ channels. They experimented with various endoplasmic reticulum export motifs and trafficking signals, including those from Kir2.1, TASK1-3, and KAT1, both alone and in combination, to find the most effective configuration. Through extensive testing, BLINK2 emerged as the candidate with the best expression efficiency and robust light regulation. This optimized design allows BLINK2 to function more effectively as an inhibitory tool, providing better neuronal inhibition with lower light intensities and longer-lasting effects.