Previously unacknowledged control point recognized as target for drugs that obstruct transition.
A new research study led by University of California, Irvine researchers is the very first to expose the specific molecular system that manages the shift from acute to persistent pain, and determines this system as a vital target for disease-modifying medications.
Findings from the research study, titled “NAAA-regulated lipid signaling governs the transition from intense to chronic pain,” released today (October 22, 2021) in Science Advances, show that disabling N-acylethanolamine acid amidase (NAAA)– an intracellular enzyme– in the back cable during a 72-hour time window following peripheral tissue injury halts chronic discomfort advancement in female and male mice.
” This study is the very first to identify that NAAA, a formerly unacknowledged control node, can be efficiently targeted by small-molecule therapeutics that inhibit this enzyme, and block the shift from severe to persistent pain,” said Daniele Piomelli, PhD, Distinguished Professor in the UCI School of Medicine Department of Anatomy & & Neurobiology. Credit: UCI School of Medicine
” Delineating the nature, localization and timing of the events associated with pain chronicity is essential to pinpointing control nodes at the same time that can be targeted by brand-new classes of disease-modifying medications beyond analgesics,” said Daniele Piomelli, Distinguished Professor in the UCI School of Medicine Department of Anatomy & & Neurobiology. “This study is the very first to recognize that NAAA, a formerly unrecognized control node, can be effectively targeted by small-molecule therapeutics that hinder this enzyme, and block the shift from severe to chronic discomfort.”
Persistent pain develops from acute pain caused by the physical injury of tissue damage due to surgery or injury and is a massive problem, affecting more than 1.5 billion individuals worldwide. Nerve damage is thought about to be a crucial element in the transition to chronic pain, however the underlying molecular occasions leading to its emergence have been improperly understood.
” Our findings recommend a new class of drugs– NAAA inhibitors– can be used to treat various kinds of persistent pain and in preventing incisional and inflammatory injuries following surgery,” Piomelli stated.
Recommendation: “NAAA-regulated lipid signaling governs the transition from acute to persistent discomfort” 22 October 2021, Science Advances.DOI: 10.1126/ sciadv.abi8834.
This work was funded by grants R41NS106999, R42DA033683 and DA041229 from the National Institutes of Health.