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CIAP and Palmitoylethanolamide (PEA) for neuropathic pain

We present a case of a 90-year old woman, born in 1920, suffering since years from axonal idiopathic neuropathy and neuropathic pain. Pain scored 7-9 on a 11-points Likert scale when I first saw her. Walking increased burining pain to a score of 9, and during resting the score was 7. On the DN-4 scale she scored 6, which is indicative for neuropathic pain. polyneuropathy.jpg

She has been seen by a neurologist in Canada, were she lives during wintertime, and he diagnosed a polyneuropathy. Most probably, as no other causes could be found, it is CIAP.

Chronic idiopathic axonal painful neuropathy, treated succesfully by palmitoylethanolamide

As the patient was totally reluctant to take anagesics such as amitriptyline and pregabeline, we started with administrating Palmitoylethanolamide (PEA),  an endogenous fatty acid amide analogue of the endocannabinoid anandamide. [1] Dose selected, amongst other sources based on a clinical trial in sciatic neuropathic pain was 600 mg twice daily.
In 2 weeks time het NRS pain score decreased from 9 to 5. On the DN-4 after 2 weeks she scored 4, a reduction of 33%.  After week 3 the pain was reduced to 2-3, and in the next weeks (weeks 3-6) the score remained stable on 2-3.  No side effects, possibly a slight clinical irrelevant reduction in bloodpressure.

PEA as analgesic

Bioactive lipids such as PEA, an anandamide analogue, were described for the first time in 1957 when it was discovered that PEA, isolated from soybeans, peanuts, and egg yolk, has anti-inflammatory properties. 1965, the group of Bachur et al found that these bioactive lipids also existed in mammalian tissues, especially in the brain.

Since the 7os of last century more than 200 entries can be found! 

Anandamide (AEA) and PEA regulate directly or indirectly many of the same pathophysiological processes, including pain perception, inflammation, convulsions and neuroprotection. 

It has been suggested that PEA enhances the effects of endocannabinoids by acting as a competitive inhibitor of the enzymatic degradation of endocannabinoids. Furthermore it is well known that anandamide can inhibit a number of different ion channels and PEA has comparable porperties and can also inhibit some potassium channels. Interestingly in isolated mitochondria PEA can dose dependently decrease generation of reactive oxygen species and thus PEA might protect mitochondria against oxidative stress.

PEA and related fatty acids in the brain have a variety of important biological effects: increase ceramide levels, inhibit of mast cell activation,  stabilize of mitochondrial function, and inhibition of degradation of anandamide that, as an endocannabinoid, can have neuroprotective effects on its own. 

Researchers from Italy assessed the efficacy and safety of palmitoylethanolamide in painful neuropathy. 30 drug naïve patients with painful neuropathy were included and treated with 600 mg Palmitoylethanolamide/day.

They clinically investigated sensory disturbances and pain using the 11-point Lickert numerical rating scale in 20 patients before and after treatment with palmitoylethanolamide. Furthermore they investigated non-nociceptive fibre function by nerve conduction study and nociceptive fibre function by laser evoked potentials.Both neuropathic pain and positive sensory symptoms significantly improved after treatment (P < 0.01), and clear trends in amplitude changes of sural and ulnar sensory nerve action potential and foot and hand LEPs were documented (P < 0.06).Their preliminary findings suggest that palmitoylethanolamide may improve nerve function and reduce neuropathic pain.

In pudendal neuropathic pain palmitoylethanolamid reduced the pain scores in a clinical relevant way. [2] In another paper the positive effects on pelvic pain were reported. [3] Animal studies are also supportive for the use of this supplement in the treatment of neuropathic pain. [4]

In our hands we see some remarkable reponses, and this patient is an example. 


A. Biasiotta, S. La Cesa, C. Leone, G. Di Stefano, A. Truini, G. Cruccu EFFICACY OF PALMITOYLETHANOLAMIDE IN PATIENTS WITH PAINFULNEUROPATHY. A CLINICAL AND NEUROPHYSIOLOGICAL OPEN STUDY.PRELIMINARY RESULTS. European Journal of Pain Supplements, Volume 4, Issue 1, May 2010, Page 77. 

Bachur, N.R., Masek, K., Melmon, K.L., et al. Fatty acid amides of ethanolamine in mammalian tissues. J Biol Chem 240 1019-1024 (1965).

Ganley, O.H., Graessle, O.E., Robinson, H.J., et al. Anti-inflammatory activity of compounds obtained from egg yolk, peanut oil, and soybean lecithin. J Lab Clin Med 51 709-714 (1958).

Devane, W.A., Hanus, L., Breuer, A., et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258 1946-1949 (1992). 

Prof. dr. Jan M Keppel Hesselink, MD, PhD, treating physician, September 2010


[1] Re G, Barbero R, Miolo A, Di Marzo V. | Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: potential use in companion animals. | Vet J. | 2007 Jan;173(1):21-30. Epub 2005 Dec 1.

[2] Calabrò RS, Gervasi G, Marino S, Mondo PN, Bramanti P. | Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide. | Pain Med. | 2010 May;11(5):781-4. Epub 2010 Mar 22.

[3] Indraccolo U, Barbieri F. | Effect of palmitoylethanolamide-polydatin combination on chronic pelvic pain associated with endometriosis: preliminary observations. | Eur J Obstet Gynecol Reprod Biol. | 2010 May;150(1):76-9. Epub 2010 Feb 21.

[4] 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.

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