Palmitoylethanolamide in inflammed tissue and in pain: reduced production and the logic of supplementing it

In the 2013 article of Sasso, in the March volume of Pain, Antinociceptive effects of the N-acylethanolamine acid amidase inhibitor ARN077 in rodent pain models, a clear picture can be seen what happens to the PEA content in inflamed tissue: it is reduced. They applied the proinflammatory phorbol ester TPA to the ear skin of  mice and this irritating substance produced local inflammation with edema. The result of the inflammation is  a reduction in tissue PEA, and a reduction of related fatty molecules with anti-inflammatory action:


The white bars are related to the PEA content before and after the pro-inflammatory compound. The black bar represents the PEA content after a inhibitor has been administered of a PEA-degrading enzyme, we see the PEA content rising again.

In inflammation there is reduced tissue content of PEA. Therefore it makes much sense to administer PEA as a supplement, to supplement the tissue with PEA, in order for PEA to exerts its anti-inflammatory effects and analgesic effects.

The result of Sasso’s experiments show that local administration of an enzyme inhibitor which catabolizes PEA, normalizes FAE levels in inflamed mouse skin and blunts the hyperalgesia and allodynia evoked in mice by carrageenan and sciatic nerve injury and in rats by ultraviolet B (UVB) radiation.

Professor Bradley K. Taylor, physiologist wrote a commentary and summerized the findings as follows. During normal states PEA is produced sufficiently to create adequate analgesia if needed. During states of injury (such as after a hernia and sciatic pain, or after an inflammation) the synthesis of PEA decreases, and less PEA is available. This leads to inadequate analgesia. Supplementing PEA increases the PEA content of the tissue and leads to increased analgesia:

PEA can lead to analgesia


Sasso O, Moreno-Sanz G, Martucci C, Realini N, Dionisi M, Mengatto L, Duranti A, Tarozzo G, Tarzia G, Mor M, Bertorelli R, Reggiani A, Piomelli D. Antinociceptive effects of the N-acylethanolamine acid amidase inhibitor ARN077 in rodent pain models. Pain. 2013 Mar;154(3):350-60. doi: 10.1016/j.pain.2012.10.018. Epub 2012 Nov 2.

Taylor BK. N-acylethanolamine acid amidase (NAAA), a new path to unleash PPAR-mediated analgesia. Pain. 2013 Mar;154(3):326-7. doi: 10.1016/j.pain.2012.12.012. Epub 2012 Dec 28.

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