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Estibaliz Urarte
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A new protein linked to chronic pain identified in a preclinical study

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Certain mutations in the gene that codes for the PIEZO2 protein increase the sensitivity of pain receptors in genetically modified mice.

According to the U.S. National Institutes of Health, 20% of the adult population suffers from chronic pain, and currently, there are no effective treatments to address it. This type of pain is closely linked to the sensitisation of pain receptors, known as nociceptors.

Recently, a team of researchers from the Max Delbrück Center for Molecular Medicine in Germany has uncovered a new role of the PIEZO2 protein related to chronic pain, a common symptom in many rare diseases. According to their findings, the PIEZO2 protein mediates hypersensitivity to chronic pain. PIEZO2 forms an ion channel (a channel that crosses the cell membrane, allowing specific ions to pass through) in human sensory neurons. We already knew this protein is involved in relaying the sense of touch to the brain. Individuals with mutations in the PIEZO2 gene that result in a loss of protein function lack sensitivity to light touch or vibrations. It has also been shown that people with "gain-of-function" mutations in PIEZO2 often suffer from complex developmental disorders. However, this study demonstrates for the first time that this specific type of mutation leads to mechanical hypersensitivity.

The study, published in the Brain journal, employed transgenic mice with gain-of-function mutations in the PIEZO2 gene. Using electrophysiological methods, researchers measured the electrical activity in sensory neurons isolated from these mice, observing that the nociceptive receptors (neurons that detect painful mechanical stimuli) were much more sensitive to mechanical stimuli.

Lead researcher Óscar Sánchez-Carranza, explains that activating nociceptors typically requires significant pressure on the skin, but in mice with these mutations, "they were activated by low levels of mechanical force, which would normally be perceived as a light touch."

Currently, most painkillers target voltage-gated sodium channels, but they have not proven to be very effective in relieving chronic pain. The findings of this study suggest that PIEZO2 channels could serve as new drug targets for pain treatment.

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