Many biological conditions cause a rise in the pH of the environment in which cells in our body exist (i.e., the environment becomes alkaline). Some of these conditions, e.g., respiratory alkalosis due to hyperventilation and the high blood pH caused by urinary tract infection, cause pain sensation, but the mechanisms by which sensory nerve cells detect alkaline pH are not well defined. However, new research, by Makoto Tominaga and colleagues, at the National Institutes of Natural Sciences, Japan, has now shown that alkaline pH activates a protein known as TRPA1 in human cell lines and mouse nerve cells. Furthermore, injection of an alkaline reagent (ammonium chloride) into the underside of the hindpaw of normal mice and mice lacking TRPA1 caused pain-related behaviors in normal mice only. As these results indicate that alkaline pH causes pain sensation in mice through activation of TRPA1, the authors suggest that activation of this protein might be the mechanism underlying some of the human alkaline pH–related pain sensations whose mechanisms are currently unknown.
TITLE: Intracellular alkalization causes pain sensation through activation of TRPA1 in mice
AUTHOR CONTACT:
Makoto Tominaga
National Institutes of Natural Sciences, Okazaki, Japan.
Phone: 0564-59-5286; Fax: 0564-59-5285; E-mail: tominaga@nips.ac.jp.
View the PDF of this article at: https://www.the-jci.org/article.php?id=35957
Journal
Journal of Clinical Investigation