Summary: Researchers have identified a natural molecule, phosphatidic acid, that reduces the sensitivity of touch ion channels, offering a promising new way to manage chronic pain.
Experiments in sensory neurons and mice showed that elevated levels of this molecule made cells less sensitive to touch, a finding that could lead to more targeted and effective treatments for conditions involving inflammatory pain.
Key Facts
Phosphatidic acid reduces the sensitivity of touch-sensing ion channels. Elevated levels of phosphatidic acid reduce intracellular touch sensitivity. Potential for new, more effective treatments for inflammatory pain.
Source: Rutgers University
Rutgers University researchers have discovered a new way to manage the receptors that control the sense of touch, which could lead to more effective treatments for chronic pain.
“The identification of a natural molecule that specifically reduces pain sensitivity offers hope for new therapeutic strategies in pain management,” said Tibor Rojas, professor in the departments of pharmacology, physiology and neuroscience at Rutgers New Jersey School of Medicine and a member of the Rutgers Brain Health Institute.
“Our goal is to translate these findings into effective treatments that improve the quality of life for people suffering from chronic pain.”
The study was authored by Matthew Gabriel, a doctoral student in the lab of Tibor Rojacs at Rutgers University New Jersey Medical School.
A natural molecule called phosphatidic acid can reduce the activity of certain touch-sensing ion channels in the body, according to a study published in the journal Nature Communications.
The researchers found that increased levels of phosphatidic acid in cells reduced sensitivity to touch, a finding confirmed by experiments on sensory neurons and tests on mice: when the formation of phosphatidic acid was inhibited, the animals became more sensitive to touch.
“This discovery adds to a growing body of evidence suggesting that lipids are important regulators of somatosensation,” Gabriel said, referring to the body’s ability to sense sensations such as touch, temperature and pain.
“By targeting the natural pathways that control these pathways, we may be able to develop more targeted and effective pain relief treatments that are particularly useful for conditions involving inflammatory pain, where current pain relief methods are often inadequate.”
About this pain research news
Author: Zhang Tongyue
Source: Rutgers University
Contact: Tongyue Zhang – Rutgers University
Image: This image is provided by Neuroscience News
Original research: Open Access.
“Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanosensitivity” Tibor Rohacs et al., Nature Communications
Abstract
Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanosensitivity
The mechanosensitive PIEZO2 ion channel plays a role in touch, proprioception, and inflammatory pain. Currently, there are no small molecule inhibitors that selectively inhibit PIEZO2 over PIEZO1.
TMEM120A protein inhibits PIEZO2 but has no effect on PIEZO1.
Here, we found that expression of TMEM120A increased intracellular levels of phosphatidic acid and lysophosphatidic acid (LPA), consistent with structural similarity to lipid-modifying enzymes.
Intracellular application of phosphatidic acid or LPA inhibits the activity of PIEZO2 but not PIEZO1, and chronic extracellular exposure to the nonhydrolyzable phosphatidic acid and LPA analog carbocyclic phosphatidic acid (ccPA) also inhibits PIEZO2.
Optogenetic activation of phospholipase D (PLD), a signaling enzyme that generates phosphatidic acid, inhibits PIEZO2 but not PIEZO1. Conversely, in behavioral experiments, inhibition of PLD increases PIEZO2 activity and increases mechanical sensitivity in mice.
These findings uncover a lipid regulator that selectively targets PIEZO2 over PIEZO1 and identify the PLD pathway as a regulator of PIEZO2 activity.
