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Palmitoylethanolamide for sciatic pain

Six hundred and thirty-six patients  affected by sciatic pain, participated in a double blind, controlled, randomised multi-centre clinical study with two doses of Palmitoylethanolamid in a non-branded formulation against a placebo, in nine hospital and university departments distributed in Italy. Palmitoylethanolamide is sold under two brandnames: Normast and PaePure.

Normast isavailable in Italy as a neurtraceutical, and as PeaPure in the Netherlands and elsewhere as a supplement. As a body own fatty compound it has minimal side effects and the analgesic effects have been evaluated in this big study. PeaPure has probably a slight advantage that it does not contain any chemical exciepient, it is pure PEA in a vetegarian capsule of 400 mg. 

Both Palmitoylethanolamid and the placebo were administered orally for 21 days.

There were only 17 drop outs. Treatment with palmitoylethanolamid 300 mg and 600 mg. At the end of the treatment period both the pain reduction and the quality of life were significantly different between the three treatment groups (p < 0.001), and the daily dose of 600 mg was significantly more effective than the dose of 300 mg/day.

Both doses of Normast® were significantly more effective than placebo  (p < 0.05).

The conclusion of the authors was: 

In effect, in patients treated with Normast® the pain and incapacity reduced much more evidently than in the patients of the placebo group, who received the classical treatments used for this condition. The results obtained demonstrate that palmitoylethanolamide (PEA) in micronised form, the active principle of Normast®, is a new molecule, effective and safe, for the treatment of chronic neuropathy pain associated with peripheral neuropathies.

The article is only available as a spanish version, and it is difficult to find out further details. However, side effect seemed to be unproblematic and sciatic pain clearly reduced making this molecule an interesting therapeutic option for neuropathic pain and sciatic pain. 

In the following video a patient demonstration of severe, Lyrica intractable pain, succesfully treated with palmitoylethanolamide. 


Palmitoylethanolamide: mechanism of action 

In preclinical animal models PEA clearly inhibits neuropathic pain. [1] EA in this model was through to act via the modulation of local mast cells degranulation, as PEA significantly reduced the production of many mediators such as TNFalpha and neurotrophic factors, like NGF. Its mechanism of action is quite broad, as central administration of palmitoylethanolamide was also shown to reduces hyperalgesia in mice via inhibition of NF-kappaB.[2]

The mechanism of action proposed by the authors is depicted below:




G. Guida1, M. de Martino, a. de Fabiani, L. Cantieri, a. aLexandre, G.M. VassaLLo, M. roGai, F. Lanaia y s. Petrosino. La palmitoiletanolamida (Normast®) en el dolor neuropático crónico por lumbociatalgia de tipo compresivo: estudio clínico multicéntrico.  DOLOR. 2010;25:35-42

December 2010, Jan M. Keppel Hesselink. MD, PhD 


[1] Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni G. | The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors. | Pain. | 2008 Oct 31;139(3):541-50. Epub 2008 Jul 3.

[2] D'Agostino G, La Rana G, Russo R, Sasso O, Iacono A, Esposito E, Mattace Raso G, Cuzzocrea S, Loverme J, Piomelli D, Meli R, Calignano A. | Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-kappaB nuclear signalling in dorsal root ganglia. | Eur J Pharmacol. | 2009 Jun 24;613(1-3):54-9. Epub 2009 Apr 20.