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PIEZO2, a gene capable of controlling the perception of one's body in space and to the touch, could also be responsible for tactile allodynia: the reaction of the skin to an injury that normally makes painful contacts painful according to a study funded by the National Institutes of Health (NIH).
This and a second study funded by the NIH, both published in Translational medicine science, used mice to show how the gene could play a critical role in the nervous system's response to injury and inflammation, making PIEZO2 a target for developing accurate treatments to relieve the pain caused by cuts, burns and other skin lesions, according to a media release from the NIH / National Institute of Neurological Disorders and Stroke.
"For years, scientists have been trying to solve the mystery of toughness. These results suggest that PIEZO2 is the gene for tactile allodynia. We hope these results will help researchers develop better treatments for managing this form of pain, "said Alexander T. Chesler, PhD, Stadtman Researcher at the National Center for Complementary and Integrative Health (NCCIH) and lead author of One of the authors. studies, in the press release.
The PIEZO2 gene encodes what scientists call a mechanosensitive protein that produces electrical nerve signals in response to changes in cell shape, for example when skin cells and neurons in the hand are squeezed against a table. Since its discovery in mice by a team led by Ardem Patapoutian, Ph.D., Scripps Research, La Jolla, CA, lead author of the second paper, scientists have proposed that PIEZO2 plays an important role in touch and pain in humans.
In 2016, the Chesler team collaborated with the group of Carsten G. Bönnemann, MD, principal investigator at the NIH's National Institute of Neurological Disorders and Stroke (NIIN), to demonstrate that two Patients with mutations of PIEZO2 having eliminated his activity lacked proprioception, or a sixth sense of how our bodies are positioned in space. They were also unable to feel the vibrations and were less sensitive to some forms of soft touch.
In this new study, Chesler and Bönnemann collaborated with NCCIH pain expert Catherine Bushnell, PhD, to examine four more patients at the NIH Clinical Center. They also discovered that PIEZO2 controlled tactile allodynia after a skin injury, the statement said.
To test allodynia, the researchers sat the participants at a table facing a barrier that blocked their view of their arms. The researchers then dabbed two creams on the participant's arm. One was a placebo, which had no effect, and the other contained capsaicin, the ingredient that makes hot peppers hot and causes inflammation, as seen with the sun burns.
The researchers found marked differences between how capsaicin affected control participants and those with mutations in PIEZO2. By passing a cotton swab around the capsaicin patch, the control group participants were constantly feeling pain, which allowed everyone to correctly identify where the inflammation was located even though they could not not see their arms. In contrast, participants with the PIEZO2 mutation did not feel any difference between the areas of application of capsaicin and placebo.
"What is remarkable about PIEZO2-deficient participants is the" clarity "of their conditions. With their help, we get new fundamental information on how the loss of PIEZO2 affects them specifically and what is the normal purpose of PIEZO2, which could be of paramount importance to all other people, "says Bönnemann.
"This type of PIEZO2-dependent pain makes it very difficult to apply bandages on burns and wounds important for healing. Most pain treatments numb large areas of the body. Our results suggest that if we could stop PIEZO2 in the area of a wound, we would hopefully relieve pain and accelerate recovery. "
Other experiments on mice conducted by Chesler and Patapoutian have confirmed the observed results in patients. The removal of PIEZO2 has eliminated the sensations of touch to the touch in mice as well as those felt during inflammation and injury. The liberation continues.
Although neither of the two studies shows exactly how inflammation causes pain, their findings suggest that inflammation does not alter the ability of PIEZO2 to detect mild contacts. For example, the Chesler group showed control mice that inflammation had no major effect on how PIEZO2-containing neurons triggered in response to gentle brushing. Instead, their findings support the door theory, which states that inflammation causes a sensation of pain to the touch because the neurons of the brain or spinal cord reinterpret the signals emitted by the rest of the body.
"It seems that inflammation does not affect the ability of skin neurons to perceive a soft touch, but instead distracts information sent to the rest of the nervous system," said Patapoutian. Concludes. "We hope these findings will help pain researchers better understand the mechanisms of tactile allodynia."
[Source(s): NIH/National Institute of Neurological Disorders and Stroke, EurekAlert]Source link
