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Archived Comments for: Inhibition of astroglial NF-kappaB enhances oligodendrogenesis following spinal cord injury

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  1. Clinical neuro-restaurative effects of palmitoylethanolamide due to Inhibition of inhibition of NF-kappaB?

    jan keppel hesselink, Institute Neuropathic Pain, the Netherlands

    6 August 2013

    Valerie Bracchi-Richard and colleagues describe their impressive experimental findings pointing out that inhibition of astroglial NF-¿B results in an altered inflammatory state that is supportive of oligodendrogenesis after spinal cord injury.

    This is a very interesting finding and there might even be some Proof Of Concept (POC) from the clinic for the relevance of this mechanism.

    In our clinic we regularly treat patients suffering from neuropathic pain with the endogenous lipid ligand palmitoylethanolamide (PEA), available as a foodsupplement. In a stroke model PEA inhibits the stroke-mediated increased expression of pJNK and NF-¿B. (1) This can be duplicated in different animal models for injury induced inflammation (2)

    Neuropathic pain recently has been redefined as gliopathic pain, and glia plays a major role in the pathogenesis of neuropathic pain. In models of neuropathic pain PEA has measurable effects related to the readout of the NF-kappaB inhibition. (3)

    Palmitoylethanolamide has proven to be of value in the treatment of neuropathic pain. (4,5) In addition to the analgesic effects, neuroprotective and neuro-restorative effects have been described, which might partly be due to oligodendrogenesis. (6) Truina et al explored the clinical effects of PEA in patients with chemotherapy induced neuropathy. They described changes in neurophysiological measures after treatment with PEA indicating that PEA exerted a positive action on myelinated fibre groups. (7) And as we all know the oligodendrocyte (Schwann cell) is the cell type responsible for myelin production.

    A comparable finding was described after the treatment of an entrapment neuropathy in the wrist, the carpal tunnel syndrome (CTS). (8) PEA treatment significantly improved the CTS-induced reduction of median nerve function.

    In our clinic we treat amongst others patients suffering from chronic idiopathic axonal neuropathy as well as chronic inflammatory neuropathy. Numbness is one of the symptoms. Some patients treated for more than 6 months with PEA are reporting a decrease in the sock and gloves patterns of numbness. We are currently looking in more detail into these neuro-restaurative properties of PEA.

    Therefore we very much welcome the seminal paper on the relevance of the Inhibition of astroglial NF-kappaB to enhance oligodendrogenesis. This mechanism of action might partly be an explanation for the clinical effects of PEA. And vice versa, the clinical findings related to PEA might be seen as a POC for the thesis of Valerie Bracchi-Ricard et al.


    1.Ahmad A, Genovese T, Impellizzeri D, Crupi R, Velardi E, Marino A, Esposito E, Cuzzocrea S. Reduction of ischemic brain injury by administration of palmitoylethanolamide after transient middle cerebral artery occlusion in rats. Brain Res. 2012 Oct 5;1477:45-58.

    2.Di Paola R, Impellizzeri D, Torre A, Mazzon E, Cappellani A, Faggio C, Esposito E, Trischitta F, Cuzzocrea S. Effects of palmitoylethanolamide on intestinal injury and inflammation caused by ischemia-reperfusion in mice. J Leukoc Biol. 2012 Jun;91(6):911-20.

    3.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.

    4. Keppel Hesselink JM, Hekker TA. Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. J Pain Res. 2012;5:437-42.

    5. Gatti A, Lazzari M, Gianfelice V, Di Paolo A, Sabato E, Sabato AF.Palmitoylethanolamide in the treatment of chronic pain caused by different etiopathogenesis. Pain Med. 2012 Sep;13(9):1121-30.

    6.Di Cesare Mannelli L, D'Agostino G, Pacini A, Russo R, Zanardelli M, Ghelardini C, Calignano A. Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy: pain relief and neuroprotection share a PPAR-alpha-mediated mechanism. Mediators Inflamm. 2013;2013:328797.

    7. Truini A, Biasiotta A, Di Stefano G, La Cesa S, Leone C, Cartoni C, Federico V, Petrucci MT, Cruccu G. Palmitoylethanolamide restores myelinated-fibre function in patients with chemotherapy-induced painful neuropathy. CNS Neurol Disord Drug Targets. 2011 Dec;10(8):916-20.

    8. Conigliaro R, Drago V, Foster PS, Schievano C, Di Marzo V. Use of palmitoylethanolamide in the entrapment neuropathy of the median in the wrist. Minerva Med. 2011 Apr;102(2):141-7.

    Competing interests

    No competing interests