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Updated: Sep 2, 2025

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Synergistic antinociceptive effects of concomitant NAAA and peripheral FAAH inhibition
Alex Mabou Tagne1, Yannick Fotio1, Parwinder Singh Uppal1
1Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697-4625, USA.
Abstract:
The intracellular lipid amidases, fatty acid amide hydrolase (FAAH) and N-acylethanolamine acid amidase (NAAA), terminate the actions of anandamide and palmitoylethanolamide (PEA), two antinociceptive and anti-inflammatory lipid-derived mediators. Here we show, confirming prior research, that small-molecule inhibitors of peripheral FAAH (compound URB937) and systemic NAAA (compound ARN19702) individually attenuate, in male CD-1 mice, pain-related behaviors and paw inflammation in the formalin and carrageenan tests. More importantly, isobolographic analyses revealed that the combination of URB937 and ARN19702 produced substantial synergistic (greater than additive) antinociceptive effects in both models as well as additive anti-inflammatory effects in the carrageenan test. Together, the findings uncover a functional interplay between FAAH and NAAA substrates in the control of nociception, which might be exploited clinically to develop safe and effective pain management strategies.
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