By Michelle Jaffee
A new study highlights the significance of a specific protein in modulating the activity of NaV1.7, a transmembrane protein critical for pain initiation and persistence. The mechanistic study, part of a line of research aimed at discovering new nonopioid-based therapies for chronic pain management, was published in the journal PNAS Nexus.
Led by MBI researcher Rajesh Khanna, Ph.D., a UF professor of pharmacology and therapeutics, the research team explored whether addition of a lipid “tag” — a type of cholesterol — by a key enzyme influences the activity of the NaV1.7 sodium channel.
Overactivity of neurons is at the root of pain signaling from the body to the brain, and when neurons are more excitable, the communication between them is amplified and registered as pain. NaV1.7 is known as one of the first components that sets that signal gone awry into motion.
In mouse cells and postmortem human sensory neurons from donors, the research team from the University of Florida and New York University investigated the role of S-palmitoylation in relation to NaV1.7. In both the mouse and human cells, they demonstrated a similar phenomenon, showing that blocking S-palmitoylation or removing amino acids where the tag is added alters the function of NaV1.7.
“What these findings illustrate is that we can tweak the activity of this key pain channel to curb neuronal excitability in a manner akin to dialing down the volume knob of pain across diverse chronic pain conditions,” Khanna said.
“We are now poised to figure out how to target this particular modification in order to design better drugs, biologics or gene therapies that can take advantage of these mechanistic findings,” he said.