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Updated: Oct 16, 2025

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
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NAAA-regulated lipid signaling governs the transition from acute to chronic pain

Yannick Fotio1, Kwang-Mook Jung1, Francesca Palese1

  • 1Department of Anatomy and Neurobiology, University of California Irvine, Irvine, CA 92697, USA.

Science Advances
|October 22, 2021
PubMed

Insights

N-acylethanolamine acid amidase (NAAA) is a key target for treating chronic pain. Inhibiting NAAA halts pain chronicity by reprogramming cellular metabolism, offering a new therapeutic strategy.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Chronic pain affects 1.5 billion people globally and is undertreated.
  • Understanding the molecular basis of chronic pain is crucial for developing new therapies.

Purpose of the Study:

  • To identify critical molecular targets for treating chronic pain.
  • To investigate the role of N-acylethanolamine acid amidase (NAAA) in pain chronicity.

Main Methods:

  • Investigated the role of NAAA in a mouse model of chronic pain.
  • Utilized small-molecule inhibitors targeting NAAA.
  • Analyzed metabolic reprogramming in the spinal cord.

Main Results:

  • Disabling NAAA in the spinal cord halted chronic pain development in mice.
  • NAAA inhibition triggered a shift from aerobic glycolysis to mitochondrial respiration.
  • This metabolic reprogramming was dependent on peroxisome proliferator-activated receptor-α (PPAR-α).

Conclusions:

  • NAAA is a critical control point in the transition to chronic pain.
  • Inhibiting NAAA represents a promising therapeutic strategy for disease-modifying pain medicines.

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