(On chronic pain) A role for proprioceptors in sngception, 2025, Lee

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https://www.science.org/doi/10.1126/sciadv.abc5219

A role for proprioceptors in sngception
Cheng-Han Lee https://orcid.org/0000-0003-3642-4115,
Jiann-Her Lin https://orcid.org/0000-0002-7255-741X,
Shing-Hong Lin https://orcid.org/0000-0002-8012-6935,
Chu-Ting Chang https://orcid.org/0000-0002-2123-301X,
Yu-Wei Wu https://orcid.org/0000-0002-4459-087X,
Guy Bewick https://orcid.org/0000-0001-8266-7797,
Robert W. Banks https://orcid.org/0000-0003-1614-6488,
Stefan Gründer https://orcid.org/0000-0002-7635-9883,
Ute Hochgeschwender https://orcid.org/0000-0001-5165-6518,
and Chih-Cheng Chen https://orcid.org/0000-0003-4768-5660

Authors Info & Affiliations
Science Advances
31 Jan 2025
Vol 11, Issue 5
DOI: 10.1126/sciadv.abc5219

10,4622
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Abstract

Proprioceptors are primary mechanosensory neurons to monitor the status of muscle contraction and/or body position (1).

Although proprioceptors are known as non-nociceptive mechanoreceptors, they also express the pro-nociceptive acid-sensing ion channel 3 (ASIC3) (2–5).

To probe the role for proprioceptors in sensing acidosis (or sngception) (6), we found that genetic deletion of Asic3 in proprioceptors but not in nociceptors abolished acid-induced chronic hyperalgesia in mice.

Chemo-optogenetically activating proprioceptors resulted in hyperalgesic priming that favored chronic pain induced by acidosis.

In humans, intramuscular acidification induced acid perception but not pain.

Conversely, in a spinal cord–injured patient who lost pain sensation in the right leg, proprioception and sngception were remaining somatosensory functions, associated with the spinal dorsal column.

Together, evidence from both mouse and human studies suggests a role for proprioceptors in sngception.
 
News release:
https://www.abdn.ac.uk/news/24440/

Groundbreaking discovery of 'new' pain target brings hope for those with chronic pain
04 June 2025

In a groundbreaking discovery, chronic pain has been shown to be physiologically different from acute pain and now scientists have the roadmap for how to target it.

Researchers from the University of Aberdeen, Academia Sinica in Taiwan and a group of international experts say the discovery brings hope for sufferers of chronic pain and fibromyalgia.

The team identified that in the nervous system chronic pain is processed differently from the pain that comes from an injury or over exertion.

Crucially, they found a new and distinct separate physiological pathway for this chronic type of pain, which means it can now be a target for future therapies.

Dr Guy Bewick, Senior Lecturer in Neurosciences at the University of Aberdeen, explains: “We all know there are different types of pain. There is the sharp stinging pain of pricking your finger with a needle, and there is also the chronic pain of muscle soreness after unaccustomed exercise. Nevertheless, most of us in the West, including scientists, regard both simply as 'pain'. Currently, Western medicine is very often ineffective for chronic pain.

“However, Eastern cultures have differentiated for many centuries, calling the latter 'sng' in Taiwanese, or 'suan tong' (sour pain) in Mandarin. The stinging pain from sharp objects and surgery can usually be treated effectively with common painkillers, but chronic pain often cannot. 

“New treatments require an identifiably different drug target. This study has found that target. Specifically, we discovered the mechanism of this pain we call 'sng’.”

The discovery of the new pain pathway is described by the team as ‘a paradigm-shifting discovery that has fundamentally changed our understanding of human sensory systems and challenged the central dogma of pain biology that has been established in the past 50 years.’

Dr Guy Bewick, and his team identified crucial evidence which laid the foundations for the discovery in Taiwan.

Dr Bewick’s team discovered that a molecule called glutamate is released in muscles to activate a highly unusual receptor. This sparked a collaboration with Professor Chen’s team in Taiwan who found that too much glutamate release activated pain nerves nearby making them permanently active and not switch off as they normally would. Crucially, they then discovered that blocking the newly discovered, highly unusual, glutamate receptor entirely stopped the chronic pain being triggered.

Dr Bewick said that: “This discovery means scientists can now start to develop new treatments specifically targeting this new pain pathway which does not respond to standard painkillers.

“This has the potential to help the many people whose pain is currently inadequately treated.”

The wider research was led by Professor Chih-Cheng Chen from Academia Sinica, supported by National Science and Technology Council’s Brain Technology Project and an Investigator Award of Academia Sinica.

They were able to differentiate between the two types of pain by genetically silencing neuronal pathways in a mouse model and then testing the theory in practice in a patient with a spinal cord injury that blocked ‘standard’ pain but spared the newly discovered pathway, in the Taipei Medical University Hospital in Taiwan.

Professor Chen explains: “Fundamentally, we found that sng persists even in people who have lost other pain sensation, for example, a patient with spinal cord damage did not notice when he had broken a toe but could still perceive 'sng' and position in the same leg.

“Clearly, therefore, sng is a separate pathway.

“The identification of a different mechanism for this type of chronic pain is an essential first step to start to develop new treatments specifically targeting this pathway, which does not respond to standard painkillers, to help the many people whose pain is currently inadequately treated.

“This finding could lead to new pain relief treatments for such conditions as fibromyalgia, exercise-induced muscle pain (DOMS), rheumatoid arthritis, and chronic pain after spinal surgery.

“It is a truly ground-breaking discovery in pain research.”

Dr Robert Banks, a Visiting Researcher in Biosciences and the Biophysical Sciences Institute of Durham University, who contributed to this work and who collaborated with Dr Bewick on the fundamental discoveries that led to it, added: “It is very pleasing that a potentially important contribution to human health has developed from our original basic scientific observations.”

published in Science Advances.

Link to full paper
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Wendy Davidson
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04 June 2025

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News / North East & Tayside

University makes 'ground-breaking' discovery offering hope for chronic pain sufferers​

Researchers hope the breakthrough will lead to new treatments for conditions such as fibromyalgia and rheumatoid arthritis.

Research: University makes 'ground-breaking discovery' for chronic pain treatment.
Anne Smith
4 hours ago

​

Posted in​

Scientists in Aberdeen have made a ground-breaking discovery that could revolutionise treatment for chronic pain.

Researchers from the University of Aberdeen, Academia Sinica in Taiwan and a group of international experts have discovered that chronic and acute pain are physiologically different.

It is hoped the breakthrough will lead to new treatments for conditions such as fibromyalgia and rheumatoid arthritis.

Marlene Lowe knows only too well what it’s like living with debilitating pain.

The 35-year-old suffers from both chronic fatigue and fibromyalgia, which causes widespread pain.

Continues at:
news.stv.tv

University makes 'ground-breaking' discovery offering hope for chronic pain sufferers

Researchers hope the breakthrough will lead to new treatments for conditions such as fibromyalgia and rheumatoid arthritis.
news.stv.tv news.stv.tv

 
Seems like proprioceptors, which we usually think of as just sensing body position, also help detect acid-related signals that can cause chronic pain. So they’re more involved in pain than people thought, especially in acid-induced pain. The part about the spinal cord injury patient still sensing acid but not pain is really cool - it shows how different sensory systems work separately.
 
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