| First Author | Fotio Y | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 43 | Pages | eabi8834 |
| PubMed ID | 34678057 | Mgi Jnum | J:314164 |
| Mgi Id | MGI:6810076 | Doi | 10.1126/sciadv.abi8834 |
| Citation | Fotio Y, et al. (2021) NAAA-regulated lipid signaling governs the transition from acute to chronic pain. Sci Adv 7(43):eabi8834 |
| abstractText | Chronic pain affects 1.5 billion people worldwide but remains woefully undertreated. Understanding the molecular events leading to its emergence is necessary to discover disease-modifying therapies. Here we show that N-acylethanolamine acid amidase (NAAA) is a critical control point in the progression to pain chronicity, which can be effectively targeted by small-molecule therapeutics that inhibit this enzyme. NAAA catalyzes the deactivating hydrolysis of palmitoylethanolamide, a lipid-derived agonist of the transcriptional regulator of cellular metabolism, peroxisome proliferator-activated receptor-α (PPAR-α). Our results show that disabling NAAA in spinal cord during a 72-h time window following peripheral tissue injury halts chronic pain development in male and female mice by triggering a PPAR-α-dependent reprogramming of local core metabolism from aerobic glycolysis, which is transiently enhanced after end-organ damage, to mitochondrial respiration. The results identify NAAA as a crucial control node in the transition to chronic pain and a molecular target for disease-modifying medicines. |
